By Gregory Seay
gseay@HartfordBusiness.com
New Haven drug developer Achillion Pharmaceuticals Inc. says its new U.S. patent covering a key compound in its treatment for hepatitis C protects it while undergoing clinical trials to bring the drug to market but also widens the door to a takeover.
Achieving patent status for its "cornerstone compound'' also elevates Achillion's attractiveness as a partner to other drug developers as well as a more attractive takeover target for pharmaceutical giants, the CEO says.
"The answer is a pretty hard 'yes,''' said Michael D. Kishbauch, a veteran pharma executive and investor who also is Achillion's chairman. "We're probably a reasonable acquisition to begin with.''
Kishbauch said the company has had previous discussions with potential partners and suitors. He did not elaborate.
Achillion has three small-molecule drugs under development to treat blood-borne ailments, including HIV.
Drug giants, such as Pfizer Inc., which has R&D operations in Connecticut, face the loss of billions in annual sales to generics as patents on their popular drugs begin to expire.
Achillion's U.S. Patent No. 7,906,619 covers composition-of-matter and method of use claims for its ACH-1625 and structurally related compounds. The patent, entitled "4-amino-4-oxobutanoyl peptides as inhibitors of viral replication," expires in 2029.
Kishbauch said patent removes the air of uncertainty among other drug developers who might want to partner with, or license from Achillion, the intellectual property at the root of the compound.
d Achillion is currently in phase 2 clinical trials with its small-molecule protease inhibitor to treat the hepatitis C virus. It is racing against other drug makers to be the first to market with an effective treatment.
"This key patent grant provides a cornerstone for Achillion's intellectual property portfolio [and] ... will make this a transformational year for Achillion," Kishbauch said.
Source
March 17, 2011
March 16, 2011
Outcomes Differ Among Hepatitis C-Related Vasculitides
Last Updated: March 16, 2011
Among patients with hepatitis C virus-related vasculitis, those with polyarteritis nodosa have a more severe and acute clinical presentation and a higher rate of clinical remission, according to a study published online Feb. 25 in Arthritis Care & Research.
WEDNESDAY, March 16 (HealthDay News) -- Among patients with hepatitis C virus (HCV)-related vasculitis, those with polyarteritis nodosa (PAN) have a more severe and acute clinical presentation and a higher rate of clinical remission, according to a study published online Feb. 25 in Arthritis Care & Research.
David Saadoun, M.D., Ph.D., of Groupe Hospitalier Pitié-Salpêtrière in Paris, and colleagues investigated the prevalence and characteristics of PAN in a cohort of 161 patients with chronic HCV-related vasculitis. The features and outcomes of 31 patients with HCV-PAN were compared with those patients with HCV-associated mixed cryoglobulinemia (HCV-MC).
The researchers found that, compared to HCV-MC, a more severe and acute presentation was seen in patients with HCV-PAN. They had more frequent fever and weight loss, severe hypertension, involvement of the gastrointestinal tract, severe and acute multifocal neuropathy, kidney and liver microaneurysms, and elevated C-reactive protein. However, clinical remission occurred in 79.3 percent of those with HCV-PAN compared to 57.5 percent of those with HCV-MC. A complete clinical response of HCV vasculitis was independently correlated with skin involvement and PAN-type vasculitis; whereas, a glomerular filtration rate less than 70 mL per minute was negatively correlated with the clinical response. Among the entire HCV-related vasculitis cohort, the five-year survival rate was 86 percent, irrespective of the type of vasculitis.
"HCV-PAN accounts for 19.3 percent of our cohort of HCV-related vasculitis. HCV-PAN compared to HCV-MC displays a more severe and acute clinical presentation, a distinct pathogenic pathway, and a higher rate of clinical remission," the authors write.
One of the study authors disclosed financial ties with several pharmaceutical companies.
Abstract
Full Text (subscription or payment may be required)
Source
Among patients with hepatitis C virus-related vasculitis, those with polyarteritis nodosa have a more severe and acute clinical presentation and a higher rate of clinical remission, according to a study published online Feb. 25 in Arthritis Care & Research.
WEDNESDAY, March 16 (HealthDay News) -- Among patients with hepatitis C virus (HCV)-related vasculitis, those with polyarteritis nodosa (PAN) have a more severe and acute clinical presentation and a higher rate of clinical remission, according to a study published online Feb. 25 in Arthritis Care & Research.
David Saadoun, M.D., Ph.D., of Groupe Hospitalier Pitié-Salpêtrière in Paris, and colleagues investigated the prevalence and characteristics of PAN in a cohort of 161 patients with chronic HCV-related vasculitis. The features and outcomes of 31 patients with HCV-PAN were compared with those patients with HCV-associated mixed cryoglobulinemia (HCV-MC).
The researchers found that, compared to HCV-MC, a more severe and acute presentation was seen in patients with HCV-PAN. They had more frequent fever and weight loss, severe hypertension, involvement of the gastrointestinal tract, severe and acute multifocal neuropathy, kidney and liver microaneurysms, and elevated C-reactive protein. However, clinical remission occurred in 79.3 percent of those with HCV-PAN compared to 57.5 percent of those with HCV-MC. A complete clinical response of HCV vasculitis was independently correlated with skin involvement and PAN-type vasculitis; whereas, a glomerular filtration rate less than 70 mL per minute was negatively correlated with the clinical response. Among the entire HCV-related vasculitis cohort, the five-year survival rate was 86 percent, irrespective of the type of vasculitis.
"HCV-PAN accounts for 19.3 percent of our cohort of HCV-related vasculitis. HCV-PAN compared to HCV-MC displays a more severe and acute clinical presentation, a distinct pathogenic pathway, and a higher rate of clinical remission," the authors write.
One of the study authors disclosed financial ties with several pharmaceutical companies.
Abstract
Full Text (subscription or payment may be required)
Source
In New York, A Rare Case of HIV Transmission From a Live Organ Donor
March 16, 2011, 5:38 PM ET
By Laura Landro
The New York State Department of Health alerted hospitals and transplant centers Tuesday that an organ recipient recently contracted the virus that causes AIDS from a live kidney donor in an unnamed city hospital. It’s the nation’s first documented case of HIV transmission via a transplant from a living donor since a sensitive test for the virus was approved and implemented for donor screening in 1985, according to the health department.
A department spokeswoman tells the Health Blog that the hospital followed acceptable protocols in an initial screening of the donor, but that he apparently had “unsafe sex” after the test and prior to donating the organ. “Of course this is a rare case, but we felt like we needed to alert centers to this possibility so they can talk to potential donors about risks and do testing closer to the time of surgery,” she says.
The state declined to name the hospital in the interest of protecting the privacy of the patient.
The department is now recommending that hospitals test donors for HIV and the hepatitis C and B viruses within 14 days before the organ donation, using nucleic acid testing. NAT can detect viral infections weeks to months before antibodies are detectable by standard serologic tests. It hasn’t been recommended for testing organs from deceased donors because of the time pressure of transplanting the organs before they deteriorate, but that time crunch shouldn’t apply to potential living donors, the state notes in its advisory.
Testing for infectious disease has all but eliminated the transmission of HIV through organ, tissue and blood donation. The Centers for Disease Control and Prevention last issued HIV-specific organ-donation screening recommendations in 1994 and is expected to update its recommendation this year.
The state is advising hospitals to question living organ donors about risky behavior, including the use of non-medical injectable drugs. Compliance with the specific recommendation is voluntary but the department is urging all centers to update their policies for screening living donors as necessary.
The transplant community’s most recent testing recommendations, which appeared in the American Journal of Transplantation last year, said that average-risk donors do not require NAT screening; they didn’t address the timing of screening. The health department says it doesn’t believe those recommendations are sufficiently protective because of the challenges of detecting behavioral risks and learning about the infection status of a donor’s sexual partners.
Source
By Laura Landro
The New York State Department of Health alerted hospitals and transplant centers Tuesday that an organ recipient recently contracted the virus that causes AIDS from a live kidney donor in an unnamed city hospital. It’s the nation’s first documented case of HIV transmission via a transplant from a living donor since a sensitive test for the virus was approved and implemented for donor screening in 1985, according to the health department.
A department spokeswoman tells the Health Blog that the hospital followed acceptable protocols in an initial screening of the donor, but that he apparently had “unsafe sex” after the test and prior to donating the organ. “Of course this is a rare case, but we felt like we needed to alert centers to this possibility so they can talk to potential donors about risks and do testing closer to the time of surgery,” she says.
The state declined to name the hospital in the interest of protecting the privacy of the patient.
The department is now recommending that hospitals test donors for HIV and the hepatitis C and B viruses within 14 days before the organ donation, using nucleic acid testing. NAT can detect viral infections weeks to months before antibodies are detectable by standard serologic tests. It hasn’t been recommended for testing organs from deceased donors because of the time pressure of transplanting the organs before they deteriorate, but that time crunch shouldn’t apply to potential living donors, the state notes in its advisory.
Testing for infectious disease has all but eliminated the transmission of HIV through organ, tissue and blood donation. The Centers for Disease Control and Prevention last issued HIV-specific organ-donation screening recommendations in 1994 and is expected to update its recommendation this year.
The state is advising hospitals to question living organ donors about risky behavior, including the use of non-medical injectable drugs. Compliance with the specific recommendation is voluntary but the department is urging all centers to update their policies for screening living donors as necessary.
The transplant community’s most recent testing recommendations, which appeared in the American Journal of Transplantation last year, said that average-risk donors do not require NAT screening; they didn’t address the timing of screening. The health department says it doesn’t believe those recommendations are sufficiently protective because of the challenges of detecting behavioral risks and learning about the infection status of a donor’s sexual partners.
Source
FDA Hepatitis Update - FDA Advisory Committee meeting to consider boceprevir and telaprevir, April 27 and April 28, 2011
From: U.S. Food & Drug Administration (FDA)
You are receiving this message as a subscriber to the FDA hepatitis electronic list serve. The purpose of the list serve is to relay important information about viral hepatitis-related products and issues, including product approvals, significant labeling changes, safety warnings, notices of upcoming public meetings and alerts to proposed regulatory guidances for comment.
Please do not reply to this message.
The Food and Drug Administration will convene its Antiviral Drugs Advisory Committee on April 27 and 28, 2011 to provide advice and recommendations to the Agency on two drugs intended to treat hepatitis C.
On April 27, 2011, from 8 a.m. to 5 p.m., the Committee will discuss a new drug application (NDA) 202–258, boceprevir (a hepatitis C virus protease inhibitor), manufactured by Merck & Co., Inc., with a proposed indication for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin (two medicines approved to treat chronic hepatitis C infection) in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.
On April 28, 2011, the committee will discuss a new drug application (NDA) 201–917, telaprevir (a hepatitis C virus protease inhibitor), manufactured by Vertex Pharmaceuticals, Inc., with a proposed indication for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin (two medicines approved to treat chronic hepatitis C infection) in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.
Compensated liver disease is a stage in which the liver is damaged but maintains ability to function.
The meeting will be held on both days from 8 a.m. to 5 p.m. at the FDA White Oak Campus, located at
10903 New Hampshire Ave., Building 31 Conference Center, the Great Room (rm. 1503), Silver Spring, MD 20993-0002.
Please note that visitors to the White Oak Campus must enter through Building 1, which is located at the circle at the entrance to the campus via Mahan Road from New Hampshire Avenue. (Google Maps)
FDA intends to make background material about these meetings available to the public no later than 2 business days before the meeting at http://www.fda.gov/AdvisoryCommittees/Calendar/default.htm.
Scroll down to the link for the Antiviral Drug Committee, and click on appropriate meeting dates.
If FDA is unable to post the background material on its Web site prior to the meeting, the background material will be made publicly available at the location of the advisory committee meeting, and the background material will be posted on FDA’s Web site after the meeting.
Public Participation Information
This FDA advisory committee meeting is free and open to the public without prior registration.
Interested persons may present data, information, or views, orally at the meeting, or in writing, on issues pending before the committee.
Written submissions may be made to
Paul Tran, R.Ph
Center for Drug Evaluation and Research
Food and Drug Administration
10903 New Hampshire Avenue
WO31-2417
Silver Spring, MD 20993-0002
Phone: 301-796-9001
Fax: 301-847-8533
E-mail: Paul.Tran@fda.hhs.gov
on or before April 14, 2011.
Oral presentations from the public will be scheduled between approximately 1:00 p.m. to 2:00 p.m., on April 28, 2011. Those desiring to make formal oral presentations should notify Paul Tran and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation on or before April 6, 2011.
Time allotted for each presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably accommodated during the scheduled open public hearing session, FDA may conduct a lottery to determine the speakers for the scheduled open public hearing session. The contact person will notify interested persons regarding their request to speak by April 7, 2011.
Please call the FDA Advisory Committee Information Line for up-to-date information on this meeting at
1-800-741-8138
(301-443-0572 in the Washington DC area)
Enter code: 3014512531
FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with physical disabilities or special needs. If you require special accommodations due to a disability, please contact Paul Tran at (301) 796-9001 at least 7 days in advance of the meeting.
Information regarding special accommodations due to a disability, or information about visitor parking and transportation may be accessed at: Public Meetings at the FDA White Oak Campus
Please visit our Web site at Public Conduct During FDA Advisory Committee Meetings for procedures on public conduct during advisory committee meetings. FDA is committed to the orderly conduct of its advisory committee meetings.
Persons attending FDA’s advisory committee meetings are advised that the agency is not responsible for providing access to electrical outlets.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
You are receiving this message as a subscriber to the FDA hepatitis electronic list serve. The purpose of the list serve is to relay important information about viral hepatitis-related products and issues, including product approvals, significant labeling changes, safety warnings, notices of upcoming public meetings and alerts to proposed regulatory guidances for comment.
Please do not reply to this message.
The Food and Drug Administration will convene its Antiviral Drugs Advisory Committee on April 27 and 28, 2011 to provide advice and recommendations to the Agency on two drugs intended to treat hepatitis C.
On April 27, 2011, from 8 a.m. to 5 p.m., the Committee will discuss a new drug application (NDA) 202–258, boceprevir (a hepatitis C virus protease inhibitor), manufactured by Merck & Co., Inc., with a proposed indication for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin (two medicines approved to treat chronic hepatitis C infection) in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.
On April 28, 2011, the committee will discuss a new drug application (NDA) 201–917, telaprevir (a hepatitis C virus protease inhibitor), manufactured by Vertex Pharmaceuticals, Inc., with a proposed indication for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin (two medicines approved to treat chronic hepatitis C infection) in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.
Compensated liver disease is a stage in which the liver is damaged but maintains ability to function.
The meeting will be held on both days from 8 a.m. to 5 p.m. at the FDA White Oak Campus, located at
10903 New Hampshire Ave., Building 31 Conference Center, the Great Room (rm. 1503), Silver Spring, MD 20993-0002.
Please note that visitors to the White Oak Campus must enter through Building 1, which is located at the circle at the entrance to the campus via Mahan Road from New Hampshire Avenue. (Google Maps)
FDA intends to make background material about these meetings available to the public no later than 2 business days before the meeting at http://www.fda.gov/AdvisoryCommittees/Calendar/default.htm.
Scroll down to the link for the Antiviral Drug Committee, and click on appropriate meeting dates.
If FDA is unable to post the background material on its Web site prior to the meeting, the background material will be made publicly available at the location of the advisory committee meeting, and the background material will be posted on FDA’s Web site after the meeting.
Public Participation Information
This FDA advisory committee meeting is free and open to the public without prior registration.
Interested persons may present data, information, or views, orally at the meeting, or in writing, on issues pending before the committee.
Written submissions may be made to
Paul Tran, R.Ph
Center for Drug Evaluation and Research
Food and Drug Administration
10903 New Hampshire Avenue
WO31-2417
Silver Spring, MD 20993-0002
Phone: 301-796-9001
Fax: 301-847-8533
E-mail: Paul.Tran@fda.hhs.gov
on or before April 14, 2011.
Oral presentations from the public will be scheduled between approximately 1:00 p.m. to 2:00 p.m., on April 28, 2011. Those desiring to make formal oral presentations should notify Paul Tran and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation on or before April 6, 2011.
Time allotted for each presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably accommodated during the scheduled open public hearing session, FDA may conduct a lottery to determine the speakers for the scheduled open public hearing session. The contact person will notify interested persons regarding their request to speak by April 7, 2011.
Please call the FDA Advisory Committee Information Line for up-to-date information on this meeting at
1-800-741-8138
(301-443-0572 in the Washington DC area)
Enter code: 3014512531
FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with physical disabilities or special needs. If you require special accommodations due to a disability, please contact Paul Tran at (301) 796-9001 at least 7 days in advance of the meeting.
Information regarding special accommodations due to a disability, or information about visitor parking and transportation may be accessed at: Public Meetings at the FDA White Oak Campus
Please visit our Web site at Public Conduct During FDA Advisory Committee Meetings for procedures on public conduct during advisory committee meetings. FDA is committed to the orderly conduct of its advisory committee meetings.
Persons attending FDA’s advisory committee meetings are advised that the agency is not responsible for providing access to electrical outlets.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
Hepatitis C virus infection in USA: an estimate of true prevalence
Liver International
Early View (Articles online in advance of print)
Eric Chak 1, Andrew H. Talal 2, Kenneth E. Sherman 3, Eugene R. Schiff 4, Sammy Saab 5
Article first published online: 15 MAR 2011
DOI: 10.1111/j.1478-3231.2011.02494.x
© 2011 John Wiley & Sons A/S
Author Information
1 Department of Medicine, UCLA-Olive View Medical Center, University of California at Los Angeles, Sylmar, CA, USA
2 Division of Gastroenterology and Hepatology and Center for the Study of Hepatitis C, Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY, USA
3 Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
4 Department of Medicine, University of Miami School of Medicine, Miami, FL, USA
5 Department of Medicine and Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
* Correspondence: Correspondence Sammy Saab, MD, MPH, AGAF, UCLA Pfleger Liver Institute, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095, USA Tel: +1 310-206-6705 Fax: +1 310-206-4197 e-mail: ssaab@mednet.ucla.edu
Abstract
Keywords :hepatitis C virus;prevalence
The recent National Health and Nutrition Examination Survey (NHANES) sampled only the civilian, non-institutionalized population of USA and may have underestimated the prevalence of hepatitis C virus (HCV) in this country. We searched the database MEDLINE, the Bureau of Justice Statistics, Center for Medicare and Medicaid and individual states Department of Corrections for all epidemiological studies regarding the prevalence of HCV in populations not sampled by the NHANES survey namely the incarcerated, homeless, nursing home residents, hospitalized and those on active military duty. Because of their relatively low frequency in the NHANES sample, we also expanded our search to include healthcare workers and long-term dialysis patients. Although included in the NHANES sample, we also performed searches on drug users (injection and non-injection) and veterans to confirm the findings of the NHANES study. Based on the prevalence of studies identified meeting our inclusion criteria, our most conservative estimates state that there at least 142 761 homeless persons, 372 754 incarcerated persons and 6805 persons on active military duty unaccounted for in the NHANES survey. While the NHANES estimates of drug users (both injection and non-injection) appear to be reasonable, the survey seems to have underestimated the number of HCV-positive veterans. Our most conservative estimates suggest that there are at least 5.2 million persons living with HCV in USA today, approximately 1.9 million of whom were unaccounted for in the NHANES survey.
Source
Early View (Articles online in advance of print)
Eric Chak 1, Andrew H. Talal 2, Kenneth E. Sherman 3, Eugene R. Schiff 4, Sammy Saab 5
Article first published online: 15 MAR 2011
DOI: 10.1111/j.1478-3231.2011.02494.x
© 2011 John Wiley & Sons A/S
Author Information
1 Department of Medicine, UCLA-Olive View Medical Center, University of California at Los Angeles, Sylmar, CA, USA
2 Division of Gastroenterology and Hepatology and Center for the Study of Hepatitis C, Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY, USA
3 Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
4 Department of Medicine, University of Miami School of Medicine, Miami, FL, USA
5 Department of Medicine and Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
* Correspondence: Correspondence Sammy Saab, MD, MPH, AGAF, UCLA Pfleger Liver Institute, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095, USA Tel: +1 310-206-6705 Fax: +1 310-206-4197 e-mail: ssaab@mednet.ucla.edu
Abstract
Keywords :hepatitis C virus;prevalence
The recent National Health and Nutrition Examination Survey (NHANES) sampled only the civilian, non-institutionalized population of USA and may have underestimated the prevalence of hepatitis C virus (HCV) in this country. We searched the database MEDLINE, the Bureau of Justice Statistics, Center for Medicare and Medicaid and individual states Department of Corrections for all epidemiological studies regarding the prevalence of HCV in populations not sampled by the NHANES survey namely the incarcerated, homeless, nursing home residents, hospitalized and those on active military duty. Because of their relatively low frequency in the NHANES sample, we also expanded our search to include healthcare workers and long-term dialysis patients. Although included in the NHANES sample, we also performed searches on drug users (injection and non-injection) and veterans to confirm the findings of the NHANES study. Based on the prevalence of studies identified meeting our inclusion criteria, our most conservative estimates state that there at least 142 761 homeless persons, 372 754 incarcerated persons and 6805 persons on active military duty unaccounted for in the NHANES survey. While the NHANES estimates of drug users (both injection and non-injection) appear to be reasonable, the survey seems to have underestimated the number of HCV-positive veterans. Our most conservative estimates suggest that there are at least 5.2 million persons living with HCV in USA today, approximately 1.9 million of whom were unaccounted for in the NHANES survey.
Source
March 15, 2011
Gilead's Hepatitis C Therapy Called Successful
CDC 3-14-11
Abstract
In early-stage study results reported recently to investors, Gilead Sciences Inc. said its four-drug combination eliminated hepatitis C virus in patients. The trial examined the use of Gilead GS-9256 and GS-9190 with the standard drugs ribavirin and peginterferon. The researchers plan to present their findings at the annual meeting of the European Association for the Study of the Liver, which begins March 30 in Berlin.
Source
http://www.sfgate.com/
Date of Publication
03/09/2011
Author
Kristen Hallam, Bloomberg News
Article Type
General media
Article Category
News Briefs
Source
Abstract
In early-stage study results reported recently to investors, Gilead Sciences Inc. said its four-drug combination eliminated hepatitis C virus in patients. The trial examined the use of Gilead GS-9256 and GS-9190 with the standard drugs ribavirin and peginterferon. The researchers plan to present their findings at the annual meeting of the European Association for the Study of the Liver, which begins March 30 in Berlin.
Source
http://www.sfgate.com/
Date of Publication
03/09/2011
Author
Kristen Hallam, Bloomberg News
Article Type
General media
Article Category
News Briefs
Source
The relationship between body mass index and age at hepatocellular carcinoma onset
Public release date: 15-Mar-2011
Contact: Ye-Ru Wang
wjg@wjgnet.com
86-105-908-0039
World Journal of Gastroenterology
The incidence and mortality associated with hepatocellular carcinoma (HCC) have been increasing worldwide, and hepatitis C virus (HCV) infection plays an important role in the pathogenesis of HCC. Previous studies have suggested that host factors, such as sex, alcohol consumption, smoking, diabetes mellitus, and obesity, are important risk factors for HCC. Meanwhile, it has been reported that HCV infection causes insulin resistance and leads to oxidative stress, potentiating fibrosis and hepatic carcinogenesis. However, the factors that influence the development of HCC in HCV-infected patients remain largely unknown.
A research article published on February 21, 2011 in the World Journal of Gastroenterology addresses this question. The authors hypothesized that obesity influences the time to onset of HCC related to HCV infection, which is reflected in the patient's age at onset. To test this hypothesis, they investigated the relationship between body mass index (BMI) and lifestyle factors and age at onset of HCC in HCV-infected patients.
The research showed that the underweight patients (BMI < 18.5 kg/m2), tended to be older at HCC onset than patients within the normal weight range (BMI 18.5 kg/m2).
The results suggest that achieving an adequate body weight along with a reduction of alcohol intake in patients with chronic hepatitis C could help prevent hepatic carcinogenesis.
###
Reference: Akiyama T, Mizuta T, Kawazoe S, Eguchi Y, Kawaguchi Y, Takahashi H, Ozaki I, Fujimoto K. Body mass index is associated with age-at-onset of HCV-infected hepatocellular carcinoma patients. World J Gastroenterol 2011; 17(7): 914-921
http://www.wjgnet.com/1007-9327/full/v17/i7/914.htm
Correspondence to: Toshihiko Mizuta, MD, PhD, Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 8498501, Japan. mizutat@med.saga-u.ac.jp
Telephone: +81-952-342362 Fax: +81-952-342017
About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H. pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2009 IF: 2.092. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
Source
Contact: Ye-Ru Wang
wjg@wjgnet.com
86-105-908-0039
World Journal of Gastroenterology
The incidence and mortality associated with hepatocellular carcinoma (HCC) have been increasing worldwide, and hepatitis C virus (HCV) infection plays an important role in the pathogenesis of HCC. Previous studies have suggested that host factors, such as sex, alcohol consumption, smoking, diabetes mellitus, and obesity, are important risk factors for HCC. Meanwhile, it has been reported that HCV infection causes insulin resistance and leads to oxidative stress, potentiating fibrosis and hepatic carcinogenesis. However, the factors that influence the development of HCC in HCV-infected patients remain largely unknown.
A research article published on February 21, 2011 in the World Journal of Gastroenterology addresses this question. The authors hypothesized that obesity influences the time to onset of HCC related to HCV infection, which is reflected in the patient's age at onset. To test this hypothesis, they investigated the relationship between body mass index (BMI) and lifestyle factors and age at onset of HCC in HCV-infected patients.
The research showed that the underweight patients (BMI < 18.5 kg/m2), tended to be older at HCC onset than patients within the normal weight range (BMI 18.5 kg/m2).
The results suggest that achieving an adequate body weight along with a reduction of alcohol intake in patients with chronic hepatitis C could help prevent hepatic carcinogenesis.
###
Reference: Akiyama T, Mizuta T, Kawazoe S, Eguchi Y, Kawaguchi Y, Takahashi H, Ozaki I, Fujimoto K. Body mass index is associated with age-at-onset of HCV-infected hepatocellular carcinoma patients. World J Gastroenterol 2011; 17(7): 914-921
http://www.wjgnet.com/1007-9327/full/v17/i7/914.htm
Correspondence to: Toshihiko Mizuta, MD, PhD, Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 8498501, Japan. mizutat@med.saga-u.ac.jp
Telephone: +81-952-342362 Fax: +81-952-342017
About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H. pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2009 IF: 2.092. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
Source
iTherX Initiates Phase 1b Study of First-in-Class Hepatitis C Virus Entry Inhibitor ITX-5061
-- Preclinical Studies Show that ITX-5061 Prevents Hepatitis C from Invading Liver Cells --
SAN DIEGO, March 15, 2011 /PRNewswire/ -- iTherX, a pharmaceutical company dedicated to discovering and developing a new class of therapies for hepatitis C, today announced that it has commenced patient recruitment in an open-label, proof-of-concept Phase 1b study of its lead compound ITX-5061 in liver transplant patients with hepatitis C virus infection (HCV). ITX-5061 represents a first-in-class compound that inhibits entry of the hepatitis C virus into liver cells.
"ITX-5061 possesses a unique mechanism of action that prevents the hepatitis C virus from entering liver cells and has demonstrated potent preclinical antiviral activity against all HCV genotypes.In addition, it has already demonstrated safety in more than 280 subjects," said Jeffrey McKelvy, PhD, MD, President and Chief Executive Officer of iTherX. "We hope ITX-5061 will significantly improve long-term transplant outcomes."
The primary objective of the Phase 1b clinical trial will be to assess the safety and tolerability of ITX-5061 in liver transplant patients. The study will also assess HCV viral load for three months after liver transplantation to determine if ITX-5061 has any immediate and/or sustained impact on viral kinetics in treated patients. Approximately 20 patients will be enrolled into one of two cohorts: one group will receive supportive care only, while the second cohort will also receive ITX-5061 at a150 mg daily dose for seven days. The trial is being conducted at the University of Birmingham, UK under the direction of David Mutimer, MBBS, MD, FRACP, FRCP, Reader in Hepatology at Birmingham University and Consultant Hepatologist to the Birmingham QE Hospital Liver and Hepatobiliary Unit.
Preclinical studies have shown ITX-5061 to be a potent and selective inhibitor of HCV entry into hepatocytes, capable of preventing virus binding/fusion and cell to cell spread, suggesting ITX-5061 may reduce re-infection rates following liver transplant.
"Recurrence of HCV infection among liver transplant patients is universal and immediate. Clinicians have long sought ways to prevent re-infection by HCV, improve transplant patient outcomes and extend survival," said Dr. Mutimer. "The potential of ITX-5061 to prevent or reduce viral infection of the new liver by halting viral-entry into healthy cells represents an extraordinarily novel approach, and we are excited to advance the clinical development of this promising antiviral compound."
The Phase 1b trial of ITX-5061 in liver transplant recipients is funded through an educational grant from iTherX with the National Institute of Health Research Biomedical Research Unit (NIH-BRU Birmingham).
This is a second clinical study for ITX-5061 in hepatitis C. The first study, a single agent placebo-controlled dose response study commenced in August 2010, is being conducted in treatment naïve chronic HCV patients by the AIDS Clinical Trial Group of the National Institute of Allergy and Infectious Diseases.
About Hepatitis C
Hepatitis C virus (HCV) infection, a disease that attacks the liver, affects 170 million people worldwide. The majority of individuals develop chronic infection and up to 20 percent of infected individuals will develop cirrhosis with the attendant risks of liver failure and liver cell cancer. The current standard of care is combination antiviral treatment with pegylated interferon-alpha and ribavirin, which results in a cure for approximately half of all patients. Unfortunately, many patients present with clinically silent infection or advanced disease, at which time antiviral treatment is generally ineffective. For these patients, liver transplantation may be the only option. End-stage liver disease due to chronic HCV infection has become the leading indication for liver transplantation in the United States. Recurrence of hepatitis C virus after liver transplantation is inevitable and disease progression is rapid when compared with disease in the non-transplanted liver.
About iTherX
iTherX is a pharmaceutical company focused on the discovery and development of a novel class of antiviral therapeutics that act by blocking entry of the hepatitis C virus into liver cells to halt the spread of infection. The company's lead program, ITX-5061, is currently in Phase 1b clinical studies intended to evaluate antiviral activity and safety in patients with HCV infection. In addition to ITX-5061, iTherX is leveraging its proprietary expertise in molecular virology and medicinal chemistry to establish a pipeline of viral entry inhibitors, with additional candidates currently undergoing preclinical testing.
CONTACTS:
BCC Partners
Karen Bergman or Susan Pietropaolo, +1.650.575.1509 or +1.845.638.6290
SOURCE iTherX
Source
SAN DIEGO, March 15, 2011 /PRNewswire/ -- iTherX, a pharmaceutical company dedicated to discovering and developing a new class of therapies for hepatitis C, today announced that it has commenced patient recruitment in an open-label, proof-of-concept Phase 1b study of its lead compound ITX-5061 in liver transplant patients with hepatitis C virus infection (HCV). ITX-5061 represents a first-in-class compound that inhibits entry of the hepatitis C virus into liver cells.
"ITX-5061 possesses a unique mechanism of action that prevents the hepatitis C virus from entering liver cells and has demonstrated potent preclinical antiviral activity against all HCV genotypes.In addition, it has already demonstrated safety in more than 280 subjects," said Jeffrey McKelvy, PhD, MD, President and Chief Executive Officer of iTherX. "We hope ITX-5061 will significantly improve long-term transplant outcomes."
The primary objective of the Phase 1b clinical trial will be to assess the safety and tolerability of ITX-5061 in liver transplant patients. The study will also assess HCV viral load for three months after liver transplantation to determine if ITX-5061 has any immediate and/or sustained impact on viral kinetics in treated patients. Approximately 20 patients will be enrolled into one of two cohorts: one group will receive supportive care only, while the second cohort will also receive ITX-5061 at a150 mg daily dose for seven days. The trial is being conducted at the University of Birmingham, UK under the direction of David Mutimer, MBBS, MD, FRACP, FRCP, Reader in Hepatology at Birmingham University and Consultant Hepatologist to the Birmingham QE Hospital Liver and Hepatobiliary Unit.
Preclinical studies have shown ITX-5061 to be a potent and selective inhibitor of HCV entry into hepatocytes, capable of preventing virus binding/fusion and cell to cell spread, suggesting ITX-5061 may reduce re-infection rates following liver transplant.
"Recurrence of HCV infection among liver transplant patients is universal and immediate. Clinicians have long sought ways to prevent re-infection by HCV, improve transplant patient outcomes and extend survival," said Dr. Mutimer. "The potential of ITX-5061 to prevent or reduce viral infection of the new liver by halting viral-entry into healthy cells represents an extraordinarily novel approach, and we are excited to advance the clinical development of this promising antiviral compound."
The Phase 1b trial of ITX-5061 in liver transplant recipients is funded through an educational grant from iTherX with the National Institute of Health Research Biomedical Research Unit (NIH-BRU Birmingham).
This is a second clinical study for ITX-5061 in hepatitis C. The first study, a single agent placebo-controlled dose response study commenced in August 2010, is being conducted in treatment naïve chronic HCV patients by the AIDS Clinical Trial Group of the National Institute of Allergy and Infectious Diseases.
About Hepatitis C
Hepatitis C virus (HCV) infection, a disease that attacks the liver, affects 170 million people worldwide. The majority of individuals develop chronic infection and up to 20 percent of infected individuals will develop cirrhosis with the attendant risks of liver failure and liver cell cancer. The current standard of care is combination antiviral treatment with pegylated interferon-alpha and ribavirin, which results in a cure for approximately half of all patients. Unfortunately, many patients present with clinically silent infection or advanced disease, at which time antiviral treatment is generally ineffective. For these patients, liver transplantation may be the only option. End-stage liver disease due to chronic HCV infection has become the leading indication for liver transplantation in the United States. Recurrence of hepatitis C virus after liver transplantation is inevitable and disease progression is rapid when compared with disease in the non-transplanted liver.
About iTherX
iTherX is a pharmaceutical company focused on the discovery and development of a novel class of antiviral therapeutics that act by blocking entry of the hepatitis C virus into liver cells to halt the spread of infection. The company's lead program, ITX-5061, is currently in Phase 1b clinical studies intended to evaluate antiviral activity and safety in patients with HCV infection. In addition to ITX-5061, iTherX is leveraging its proprietary expertise in molecular virology and medicinal chemistry to establish a pipeline of viral entry inhibitors, with additional candidates currently undergoing preclinical testing.
CONTACTS:
BCC Partners
Karen Bergman or Susan Pietropaolo, +1.650.575.1509 or +1.845.638.6290
SOURCE iTherX
Source
March 14, 2011
A wild ride in Hepatitis C treatment
A wild ride in Hepatitis C treatment: Vertex stock gives investors whiplash
March 14th, 2011 5:56 pm ET
Elisabeth Morris
Boston Health News Examiner
Has anyone noticed that Vertex Pharmaceuticals, Cambridge MA (VRTX, Nasdaq) stock has been bouncing around like a ping pong ball during the last months? Traders have been consistently excited about the positive news from Vertex’s Hepatitis C virus (HCV) treatment telaprevir. And some news about a treatment for cystic fibrosis pushed the stock to it’s 52 week high on March 4. But investors reacted (or should we say over-reacted) quite strikingly to some extremely early, positive (but as yet unpublished) results from a very short and small study testing efficacy of Pharmaset’s Hepatitis C treatment, and Vertex’s stock lost 12% of it’s value abruptly last week. Now Vertex stock is undergoing a small uptick based on positive results from it’s anti-inflammatory to treat epilepsy. What a roller coaster ride! It is really very unlikely that any of these results justify such large changes in the value of the company’s stock.
Let’s go back to telaprevir, the treatment for Hepatitis C that is the foundation of Vertex’s value at this point. Hepatitis C virus is a leading cause of chronic liver disease in the United States, and it is estimated that 170 million people worldwide have clinical signs from Hepatitis C virus infection. HCV can cause acute liver disease with severe symptoms, but about 75% of patients develop chronic HCV which can vary from asymptomatic to chronic liver failure and cirrhosis over a course of 10-20 years. HCV is a enveloped, single stranded RNA virus which infects liver cells, proliferates in the cell and then goes on to infect many more cells with each replication process. The end result is destruction of the liver. The viral replication process requires the virus to make an enzyme called NS3/4A. When telaprevir is in the circulation, it binds to the NS3/4A enzyme and prevents the virus from proliferating in the liver cell.
Present standard of care for Hepatitis C infection is a combination therapy of pegylated interferon alpha plus ribavirin for 24-48 weeks. Approximately 70-80% of patients infected with Hepatitis Virus type 2 and type 3 respond to this treatment, whereas Hepatitis Virus type 1 is only successfully treated in 40% of patients. Success is measured as ‘sustained virological response’ or SVR, where the virus is undetectable 24 weeks after therapy has ended. The treatment plan for telaprevir is to add it to the combination of interferon and ribavirin, and the desired result is an improvement in the per cent of patients with SVR in Hepatitis Virus type 1 patients previously untreated. In addition, Vertex investigated whether treatment of patients who did not respond to interferon and ribavirin, or who responded and then relapsed would achieve SVR by repeat treatment with the addition of telaprevir.
Vertex filed a NDA in November 2010, and was granted a 6 month priority review by the FDA, which reduced the time for the FDA to evaluate the submission from 10 months to 6 months. The data in the NDA was based on three studies. Two recruited people never before treated for Hepatitis C and treated them with a combination of pegylated interferon, ribavirin and telaprevir. 75% achieved a viral cure (SVR) with telaprevir-based combination therapy, compared to 44% of people who received pegylated-interferon and ribavirin alone; The data showed there was no benefit to extending total treatment from 24 weeks to 48 weeks in people who responded quickly, so treatment time was cut in half for many patients. The third study was done in people with hepatitis C who had not achieved a viral cure with a prior course of treatment. 83% of prior relapsers and 29% of prior non-responders achieved a viral cure with telaprevir-based combination therapy compared to 24%, and 5% of people in these subgroups, respectively, who received pegylated-interferon and ribavirin alone. This result, in particular, is quite exciting, as prior to the availability of telaprevir, non-responders or relapsers had only a tiny hope of improved response with a second course of ribavirin/pegylated interferon therapy. In March, Vertex reported that telaprevir helped eliminate the hepatitis C virus in 70 percent of patients who were also infected with HIV, according to interim analysis from a small midstage clinical trial. The interim analysis looked for a rapid viral response (RVR), meaning the hepatitis C virus was undetectable in the blood after four weeks of treatment.
Vertex has stiff competition from Merck, who also filed an NDA for boceprevir for treatment of Hepatitis C in studies designed similarly to those for telaprevir. Boceprevir has the same mechanism of action against the Hepatitic C virus as telaprevir. Efficacy was similar for boceprevir and telaprevir, but Merck is grappling with anemia as a side effect of boceprevir, and the anemia is severe enough to require treatment with recombinant erythropoietin. Although more than 20 other drugs are in development for Hepatitis C, the advanced state of telaprevir and boceprevir, and the good results with both will require that any new drugs differentiate themselves by complete elimination of the virus, or an advance that would not require combination with pegylated interferon and ribavirin, both of which cause clinically important side effects.
Back to Vertex and it’s wild stock ride. In May 2009, Vertex stock was trading at $29, and it slowly rose to $37 in May 2010 after phase 2 results for telaprevir were reported. The stock hit $47 after the filing of the NDA and then the release of the recent study in patients co-infected with Hepatitis C and HIV. In February Vertex released some results for VX-770, a genetic treatment for 4% of cystic fibrosis patients (1) with a genetic mutation known as G551D. Patients with the G551D mutation have sufficient cystic fibrosis transporter proteins on the surface of cells but the proteins are damaged and don't work correctly. VX-770 is a "potentiator" designed to improve the function of the damaged CFTR proteins, thereby fixing the root cause of cystic fibrosis in these patients. Although this drug will be targeted to a very small subpopulation of cystic fibrosis patients, those with the gene mutation G551D sustained a 10.6% improvement in lung function. Vertex had designated a 4.5% improvement as a positive endpoint for this study, so these results are solidly positive. Based on this result, Vertex’s stock rose to a 52 week high of 51.07 on March 4.
Just last week, at the International Liver Congress in Berlin, Pharmaset, a Princeton, NJ biotech company presented a poster which claimed that combination therapy with 2 nucleotide analogs resulted in 95-100% of patients with no detectable Hepatitis C virus 4 weeks after initiation of treatment. While quite promising, this type of viral therapy has been around since the development of AZT which was approved by the FDA for treatment of HIV in 1987. While Pharmaset’s dual therapies demonstrated increased efficacy compared to treatment with either drug alone, the study reported results in only 30 patients. Nucleotide analogs are well understood, and typically induce viral resistance with sustained use. The use of 2 different analogs together may circumvent this problem, but much longer studies are needed to be able to predict the success of the Pharmaset drugs for treatment of Hepatitis C. But this study does generate excitement centered around the fulfilling of the 2 remaining goals for Hepatitis C virus treatment: Complete elimination of the virus, and removal of requirement for treatment with interferon and ribavirin. But based on this very early, very short study in 30 patients, Vertex’s stock plummeted 12% to $44.80 on March 10. It is way too premature to predict what effect the Pharmaset drugs will have on the market for telaprevir.
Luckily, on that same day, Vertex fought back by releasing positive safety and tolerability goals in a midstage study of an anti-inflammatory for treatment-resistant epilepsy, a type of epilepsy where seizures start and occur in a specific part of the brain. The study enrolled and dosed people who had not benefitted from the use of at least two currently available medicines. While the drug was safe, efficacy was not significant. But, greater improvements were observed in the last two weeks of the treatment phase and first two weeks of the follow-up period, which suggests that a longer-duration study may be needed to evaluate the effectiveness of the drug. Vertex expects to begin this study as early as the fourth quarter.
Source
March 14th, 2011 5:56 pm ET
Elisabeth Morris
Boston Health News Examiner
Has anyone noticed that Vertex Pharmaceuticals, Cambridge MA (VRTX, Nasdaq) stock has been bouncing around like a ping pong ball during the last months? Traders have been consistently excited about the positive news from Vertex’s Hepatitis C virus (HCV) treatment telaprevir. And some news about a treatment for cystic fibrosis pushed the stock to it’s 52 week high on March 4. But investors reacted (or should we say over-reacted) quite strikingly to some extremely early, positive (but as yet unpublished) results from a very short and small study testing efficacy of Pharmaset’s Hepatitis C treatment, and Vertex’s stock lost 12% of it’s value abruptly last week. Now Vertex stock is undergoing a small uptick based on positive results from it’s anti-inflammatory to treat epilepsy. What a roller coaster ride! It is really very unlikely that any of these results justify such large changes in the value of the company’s stock.
Let’s go back to telaprevir, the treatment for Hepatitis C that is the foundation of Vertex’s value at this point. Hepatitis C virus is a leading cause of chronic liver disease in the United States, and it is estimated that 170 million people worldwide have clinical signs from Hepatitis C virus infection. HCV can cause acute liver disease with severe symptoms, but about 75% of patients develop chronic HCV which can vary from asymptomatic to chronic liver failure and cirrhosis over a course of 10-20 years. HCV is a enveloped, single stranded RNA virus which infects liver cells, proliferates in the cell and then goes on to infect many more cells with each replication process. The end result is destruction of the liver. The viral replication process requires the virus to make an enzyme called NS3/4A. When telaprevir is in the circulation, it binds to the NS3/4A enzyme and prevents the virus from proliferating in the liver cell.
Present standard of care for Hepatitis C infection is a combination therapy of pegylated interferon alpha plus ribavirin for 24-48 weeks. Approximately 70-80% of patients infected with Hepatitis Virus type 2 and type 3 respond to this treatment, whereas Hepatitis Virus type 1 is only successfully treated in 40% of patients. Success is measured as ‘sustained virological response’ or SVR, where the virus is undetectable 24 weeks after therapy has ended. The treatment plan for telaprevir is to add it to the combination of interferon and ribavirin, and the desired result is an improvement in the per cent of patients with SVR in Hepatitis Virus type 1 patients previously untreated. In addition, Vertex investigated whether treatment of patients who did not respond to interferon and ribavirin, or who responded and then relapsed would achieve SVR by repeat treatment with the addition of telaprevir.
Vertex filed a NDA in November 2010, and was granted a 6 month priority review by the FDA, which reduced the time for the FDA to evaluate the submission from 10 months to 6 months. The data in the NDA was based on three studies. Two recruited people never before treated for Hepatitis C and treated them with a combination of pegylated interferon, ribavirin and telaprevir. 75% achieved a viral cure (SVR) with telaprevir-based combination therapy, compared to 44% of people who received pegylated-interferon and ribavirin alone; The data showed there was no benefit to extending total treatment from 24 weeks to 48 weeks in people who responded quickly, so treatment time was cut in half for many patients. The third study was done in people with hepatitis C who had not achieved a viral cure with a prior course of treatment. 83% of prior relapsers and 29% of prior non-responders achieved a viral cure with telaprevir-based combination therapy compared to 24%, and 5% of people in these subgroups, respectively, who received pegylated-interferon and ribavirin alone. This result, in particular, is quite exciting, as prior to the availability of telaprevir, non-responders or relapsers had only a tiny hope of improved response with a second course of ribavirin/pegylated interferon therapy. In March, Vertex reported that telaprevir helped eliminate the hepatitis C virus in 70 percent of patients who were also infected with HIV, according to interim analysis from a small midstage clinical trial. The interim analysis looked for a rapid viral response (RVR), meaning the hepatitis C virus was undetectable in the blood after four weeks of treatment.
Vertex has stiff competition from Merck, who also filed an NDA for boceprevir for treatment of Hepatitis C in studies designed similarly to those for telaprevir. Boceprevir has the same mechanism of action against the Hepatitic C virus as telaprevir. Efficacy was similar for boceprevir and telaprevir, but Merck is grappling with anemia as a side effect of boceprevir, and the anemia is severe enough to require treatment with recombinant erythropoietin. Although more than 20 other drugs are in development for Hepatitis C, the advanced state of telaprevir and boceprevir, and the good results with both will require that any new drugs differentiate themselves by complete elimination of the virus, or an advance that would not require combination with pegylated interferon and ribavirin, both of which cause clinically important side effects.
Back to Vertex and it’s wild stock ride. In May 2009, Vertex stock was trading at $29, and it slowly rose to $37 in May 2010 after phase 2 results for telaprevir were reported. The stock hit $47 after the filing of the NDA and then the release of the recent study in patients co-infected with Hepatitis C and HIV. In February Vertex released some results for VX-770, a genetic treatment for 4% of cystic fibrosis patients (1) with a genetic mutation known as G551D. Patients with the G551D mutation have sufficient cystic fibrosis transporter proteins on the surface of cells but the proteins are damaged and don't work correctly. VX-770 is a "potentiator" designed to improve the function of the damaged CFTR proteins, thereby fixing the root cause of cystic fibrosis in these patients. Although this drug will be targeted to a very small subpopulation of cystic fibrosis patients, those with the gene mutation G551D sustained a 10.6% improvement in lung function. Vertex had designated a 4.5% improvement as a positive endpoint for this study, so these results are solidly positive. Based on this result, Vertex’s stock rose to a 52 week high of 51.07 on March 4.
Just last week, at the International Liver Congress in Berlin, Pharmaset, a Princeton, NJ biotech company presented a poster which claimed that combination therapy with 2 nucleotide analogs resulted in 95-100% of patients with no detectable Hepatitis C virus 4 weeks after initiation of treatment. While quite promising, this type of viral therapy has been around since the development of AZT which was approved by the FDA for treatment of HIV in 1987. While Pharmaset’s dual therapies demonstrated increased efficacy compared to treatment with either drug alone, the study reported results in only 30 patients. Nucleotide analogs are well understood, and typically induce viral resistance with sustained use. The use of 2 different analogs together may circumvent this problem, but much longer studies are needed to be able to predict the success of the Pharmaset drugs for treatment of Hepatitis C. But this study does generate excitement centered around the fulfilling of the 2 remaining goals for Hepatitis C virus treatment: Complete elimination of the virus, and removal of requirement for treatment with interferon and ribavirin. But based on this very early, very short study in 30 patients, Vertex’s stock plummeted 12% to $44.80 on March 10. It is way too premature to predict what effect the Pharmaset drugs will have on the market for telaprevir.
Luckily, on that same day, Vertex fought back by releasing positive safety and tolerability goals in a midstage study of an anti-inflammatory for treatment-resistant epilepsy, a type of epilepsy where seizures start and occur in a specific part of the brain. The study enrolled and dosed people who had not benefitted from the use of at least two currently available medicines. While the drug was safe, efficacy was not significant. But, greater improvements were observed in the last two weeks of the treatment phase and first two weeks of the follow-up period, which suggests that a longer-duration study may be needed to evaluate the effectiveness of the drug. Vertex expects to begin this study as early as the fourth quarter.
Source
Incidence and Risk Factors for Steatosis Progression in Adults Coinfected With HIV and Hepatitis C Virus
Gastroenterology
Volume 140, Issue 3 , Pages 809-817, March 2011
Tinsay A. Woreta, Catherine G. Sutcliffe, Shruti H. Mehta, Todd T. Brown, Yvonne Higgins, David L. Thomas, Michael S. Torbenson, Richard D. Moore, Mark S. Sulkowski
Received 24 May 2010; accepted 22 November 2010. published online 06 December 2010.
Abstract
Background & Aims
Hepatic steatosis is a common histologic finding in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), although little is known about its natural history. We prospectively examined the natural history of steatosis in patients coinfected with HIV and HCV who attended an urban HIV clinic.
Methods
The study cohort consisted of 222 coinfected patients (87% black, 94% with HCV genotype 1 infection) who had at least 2 liver biopsies performed between 1993 and 2008. Biopsy specimens were scored by a single pathologist; samples were classified as having trivial (<5% of hepatocytes affected) or significant (>5%) levels of fat (steatosis). We characterized progression to significant levels of fat among patients whose first biopsy samples had no or trivial levels of fat, and regression among those with significant fat, using logistic regression.
Results
Initial biopsy specimens from most patients (88%) had no or trivial amounts of fat. Among second biopsy samples, 74% had no or trivial fat and 13% had significant amounts of fat. The strongest risk factors for progression of steatosis were alcohol abuse and overweight/obesity; cumulative exposure to antiretroviral therapy between biopsies and high counts of CD4+ T cells were associated with reduced progression of steatosis. Among the 28 patients whose initial biopsy specimen had significant fat levels, most (75%) regressed.
Conclusions
Antiretroviral therapy and high counts of CD4+ T cells are associated with reduced progression of steatosis in patients coinfected with HIV and HCV. Efforts to diagnose and prevent steatosis should focus on persons with a high body mass index and excessive alcohol intake.
Keywords: Pathology, Cirrhosis, AIDS, Liver Disease
Source
Volume 140, Issue 3 , Pages 809-817, March 2011
Tinsay A. Woreta, Catherine G. Sutcliffe, Shruti H. Mehta, Todd T. Brown, Yvonne Higgins, David L. Thomas, Michael S. Torbenson, Richard D. Moore, Mark S. Sulkowski
Received 24 May 2010; accepted 22 November 2010. published online 06 December 2010.
Abstract
Background & Aims
Hepatic steatosis is a common histologic finding in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), although little is known about its natural history. We prospectively examined the natural history of steatosis in patients coinfected with HIV and HCV who attended an urban HIV clinic.
Methods
The study cohort consisted of 222 coinfected patients (87% black, 94% with HCV genotype 1 infection) who had at least 2 liver biopsies performed between 1993 and 2008. Biopsy specimens were scored by a single pathologist; samples were classified as having trivial (<5% of hepatocytes affected) or significant (>5%) levels of fat (steatosis). We characterized progression to significant levels of fat among patients whose first biopsy samples had no or trivial levels of fat, and regression among those with significant fat, using logistic regression.
Results
Initial biopsy specimens from most patients (88%) had no or trivial amounts of fat. Among second biopsy samples, 74% had no or trivial fat and 13% had significant amounts of fat. The strongest risk factors for progression of steatosis were alcohol abuse and overweight/obesity; cumulative exposure to antiretroviral therapy between biopsies and high counts of CD4+ T cells were associated with reduced progression of steatosis. Among the 28 patients whose initial biopsy specimen had significant fat levels, most (75%) regressed.
Conclusions
Antiretroviral therapy and high counts of CD4+ T cells are associated with reduced progression of steatosis in patients coinfected with HIV and HCV. Efforts to diagnose and prevent steatosis should focus on persons with a high body mass index and excessive alcohol intake.
Keywords: Pathology, Cirrhosis, AIDS, Liver Disease
Source
FDA Panel To Review Merck, Vertex Hepatitis Drugs In Late April
March 14, 2011, 11:52 A.M. ET
By Thomas Gryta
Of DOW JONES NEWSWIRES
NEW YORK (Dow Jones)--A U.S. Food and Drug Administration panel will review two hepatitis C drugs in development from Vertex Pharmaceuticals Inc. (VRTX) and Merck & Co. Inc. (MRK) in late April, as the companies race to compete against each other in a potentially lucrative market.
The agency's Antiviral Drugs Advisory Committee will review Merck's boceprevir on April 27 and Vertex's telaprevir on April 28. The widely expected reviews will have outside experts recommend whether the agency should allow the drugs on the market.
Both drugs have shown success in increasing the cure rates of the liver disease when added to current treatments.
They are expected to come to the market at similar times and be widely used, creating a market share battle. Merck said in early January that it was granted a six-month review; Vertex is getting a similar review and expects a decision by May 23.
Many on Wall Street believe that clinical trials show Vertex's telaprevir is the preferable drug, although Merck's Chief Executive Kenneth Frazier has repeatedly stated his confidence in boceprevir's prospects.
Wells Fargo recently projected $1.4 billion in U.S. sales next year for telaprevir. Vertex owns the North American rights to the drug and would get a royalty on overseas sales from partner Johnson & Johnson (JNJ).
Hepatitis C is a blood-transmitted virus that causes liver inflammation and can lead to cirrhosis, cancer and liver failure.
Both the Merck and Vertex drugs are known as protease inhibitors, which are designed to block an enzyme that helps the hepatitis C virus replicate. Standard treatment is a combination of the drug pegylated interferon and ribavirin, but adding the new drugs may improve cure rates and shorten the duration of treatment.
- By Thomas Gryta, Dow Jones Newswires; 212-416-2169; thomas.gryta@dowjones.com
Source
By Thomas Gryta
Of DOW JONES NEWSWIRES
NEW YORK (Dow Jones)--A U.S. Food and Drug Administration panel will review two hepatitis C drugs in development from Vertex Pharmaceuticals Inc. (VRTX) and Merck & Co. Inc. (MRK) in late April, as the companies race to compete against each other in a potentially lucrative market.
The agency's Antiviral Drugs Advisory Committee will review Merck's boceprevir on April 27 and Vertex's telaprevir on April 28. The widely expected reviews will have outside experts recommend whether the agency should allow the drugs on the market.
Both drugs have shown success in increasing the cure rates of the liver disease when added to current treatments.
They are expected to come to the market at similar times and be widely used, creating a market share battle. Merck said in early January that it was granted a six-month review; Vertex is getting a similar review and expects a decision by May 23.
Many on Wall Street believe that clinical trials show Vertex's telaprevir is the preferable drug, although Merck's Chief Executive Kenneth Frazier has repeatedly stated his confidence in boceprevir's prospects.
Wells Fargo recently projected $1.4 billion in U.S. sales next year for telaprevir. Vertex owns the North American rights to the drug and would get a royalty on overseas sales from partner Johnson & Johnson (JNJ).
Hepatitis C is a blood-transmitted virus that causes liver inflammation and can lead to cirrhosis, cancer and liver failure.
Both the Merck and Vertex drugs are known as protease inhibitors, which are designed to block an enzyme that helps the hepatitis C virus replicate. Standard treatment is a combination of the drug pegylated interferon and ribavirin, but adding the new drugs may improve cure rates and shorten the duration of treatment.
- By Thomas Gryta, Dow Jones Newswires; 212-416-2169; thomas.gryta@dowjones.com
Source
New Hepatitis C Data from Boehringer Ingelheim HCV Portfolio to Be Presented at EASL
March 14, 2011 03:00 AM Eastern Daylight Time
INGELHEIM, Germany--(BUSINESS WIRE)--For Non- U.S. Media only
New data from the Boehringer Ingelheim hepatitis C virus (HCV) portfolio will be presented in oral scientific sessions at the International Liver CongressTM 2011, the 46th Annual Meeting of the European Association for the Study of the Liver (EASL), taking place 30 March-3 April in Berlin, Germany. The data will include final results from SILEN-C1 and SILEN-C2, two Phase IIb studies evaluating one of Boehringer Ingelheim’s investigational compounds for Hepatitis C treatment, the once-daily, oral protease inhibitor BI 201335 in combination with the current standard-of-care (pegylated-interferon and ribavirin).
Oral presentations (Friday, 1 April, 2011; Parallel Session: HCV Drug Development, Hall 1)
• SILEN-C1: Sustained Virologic Response (SVR) and safety of BI201335 combined with peginterferon alfa-2a and ribavirin (P/R) in treatment-naïve patients with chronic genotype 1 HCV infection
(Abstract 60. M. Sulkowski, et al. 16:00h - 16:15h)
• SILEN-C2: Sustained Virologic Response (SVR) and safety of BI201335 combined with peginterferon alfa-2a and ribavirin (P/R) in chronic HCV genotype-1 patients with non-response to P/R
(Abstract 66. M. Sulkowski, et al. 17:30h - 17:45h)
Boehringer Ingelheim is continuing its long heritage in virology and is dedicated to developing new medicines to improve treatment for HCV patients. BI 201335 is part of a growing HCV portfolio that is being investigated with the aim of identifying a simpler HCV cure, overcoming the challenges of current treatments.
Additional HCV studies to be presented at EASL
• SVR and Pharmacokinetics of the HCV protease inhibitor BI201335 with PegIFN/RBV in HCV genotype-1 patients with compensated liver cirrhosis and non-response to previous PegIFN/RBV
(Poster 1231. S. Pol, et al.; Saturday, 2 April, 2011, 09:00h - 18:00h)
• Mechanisms of isolated unconjugated hyperbilirubinemia induced by the HCV NS3/4A protease inhibitor BI201335 (Poster 1236. R. Sane, et al.;Saturday, 2 April, 2011, 09:00h - 18:00h)
• BI201335 Pharmacokinetics and early effect on viral load in HCV genotype-1 patients
(Poster 1249. C. Yong, et al.;Saturday, April 2, 2011, 09:00h - 18:00h)
• Preclinical Characterization of the hepatitis C virus NS5B polymerase non-nucleoside inhibitor BILB 1941 (Poster 1215. G. Kukolj et. al.; Friday, 30 March, 2011, 09:00h - 18:00h)
The abstracts can be accessed through the EASL website, http://www.easl.eu/.
For more information on BI’s hepatitis portfolio, please visit www.boehringer-ingelheim.com and follow us on Twitter. www.twitter.com/boehringer.
Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
Within the company’s global research network, Virology is one of the seven R&D areas with focus on Hepatitis C.
In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro (US $17.7 billion) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.
Contacts
Boehringer Ingelheim GmbH
Julia Meyer-Kleinmann
Director Corporate Communications
55216 Ingelheim/Germany
Phone: + 49 - 6132 – 77 8271 / Fax: + 49 - 6132 – 77 70 77
E-mail: press@boehringer-ingelheim.com
Source
INGELHEIM, Germany--(BUSINESS WIRE)--For Non- U.S. Media only
New data from the Boehringer Ingelheim hepatitis C virus (HCV) portfolio will be presented in oral scientific sessions at the International Liver CongressTM 2011, the 46th Annual Meeting of the European Association for the Study of the Liver (EASL), taking place 30 March-3 April in Berlin, Germany. The data will include final results from SILEN-C1 and SILEN-C2, two Phase IIb studies evaluating one of Boehringer Ingelheim’s investigational compounds for Hepatitis C treatment, the once-daily, oral protease inhibitor BI 201335 in combination with the current standard-of-care (pegylated-interferon and ribavirin).
Oral presentations (Friday, 1 April, 2011; Parallel Session: HCV Drug Development, Hall 1)
• SILEN-C1: Sustained Virologic Response (SVR) and safety of BI201335 combined with peginterferon alfa-2a and ribavirin (P/R) in treatment-naïve patients with chronic genotype 1 HCV infection
(Abstract 60. M. Sulkowski, et al. 16:00h - 16:15h)
• SILEN-C2: Sustained Virologic Response (SVR) and safety of BI201335 combined with peginterferon alfa-2a and ribavirin (P/R) in chronic HCV genotype-1 patients with non-response to P/R
(Abstract 66. M. Sulkowski, et al. 17:30h - 17:45h)
Boehringer Ingelheim is continuing its long heritage in virology and is dedicated to developing new medicines to improve treatment for HCV patients. BI 201335 is part of a growing HCV portfolio that is being investigated with the aim of identifying a simpler HCV cure, overcoming the challenges of current treatments.
Additional HCV studies to be presented at EASL
• SVR and Pharmacokinetics of the HCV protease inhibitor BI201335 with PegIFN/RBV in HCV genotype-1 patients with compensated liver cirrhosis and non-response to previous PegIFN/RBV
(Poster 1231. S. Pol, et al.; Saturday, 2 April, 2011, 09:00h - 18:00h)
• Mechanisms of isolated unconjugated hyperbilirubinemia induced by the HCV NS3/4A protease inhibitor BI201335 (Poster 1236. R. Sane, et al.;Saturday, 2 April, 2011, 09:00h - 18:00h)
• BI201335 Pharmacokinetics and early effect on viral load in HCV genotype-1 patients
(Poster 1249. C. Yong, et al.;Saturday, April 2, 2011, 09:00h - 18:00h)
• Preclinical Characterization of the hepatitis C virus NS5B polymerase non-nucleoside inhibitor BILB 1941 (Poster 1215. G. Kukolj et. al.; Friday, 30 March, 2011, 09:00h - 18:00h)
The abstracts can be accessed through the EASL website, http://www.easl.eu/.
For more information on BI’s hepatitis portfolio, please visit www.boehringer-ingelheim.com and follow us on Twitter. www.twitter.com/boehringer.
Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
Within the company’s global research network, Virology is one of the seven R&D areas with focus on Hepatitis C.
In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro (US $17.7 billion) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.
Contacts
Boehringer Ingelheim GmbH
Julia Meyer-Kleinmann
Director Corporate Communications
55216 Ingelheim/Germany
Phone: + 49 - 6132 – 77 8271 / Fax: + 49 - 6132 – 77 70 77
E-mail: press@boehringer-ingelheim.com
Source
Inovio Pharmaceuticals' Partner ChronTech Initiates Phase II Clinical Trial of Hepatitis C Virus DNA Vaccine Using Inovio's Electroporation Delivery Technology
In Phase I trial 83% of patients showed undetectable hepatitis C virus levels
BLUE BELL, Pa., March 14, 2011 /PRNewswire/ -- Inovio Pharmaceuticals, Inc. (NYSE Amex: INO), a leader in the development of therapeutic and preventive vaccines against cancers and infectious diseases, announced today that its partner, ChronTech Pharma AB (formerly Tripep AB), has initiated a Phase IIb clinical study of its ChronVac-C® DNA vaccine for hepatitis C virus (HCV), delivered by Inovio's proprietary electroporation DNA vaccine delivery technology, in combination with standard of care.
In a Phase I clinical trial of ChronVac-C using Inovio's MedPulser® electroporation device the therapy resulted in a robust increase in T-cell immune responses against HCV and was safe and well-tolerated. Post-study observation of subjects who completed the protocol and then entered into standard of care (SOC) treatment using interferon and ribavirin showed a complete and rapid viral response (four weeks) in 70% of those participants (5 of 7 patients). More significantly, 83% of the participants (5 of 6 patients) who were monitored for an extended period of time, continued to be free of the virus six months after they completed SOC. SOC treatment alone usually results in about 40-50% of patients reaching undetectable virus levels after six months of treatment.
This Phase II follow-on trial is an open-label, single-dose, randomized trial of 32 patients to further explore the effect of the ChronVac-C® DNA vaccine administered by Inovio's MedPulser® electroporation delivery device. The therapy will be given two times, with four weeks in between, followed by SOC treatment after the final vaccine dose in treatment-naïve chronic HCV infected genotype-1 subjects. This trial will assess the level of immune responses, levels of HCV viral load, and further assess the response to the delivery technology. Twenty patients will receive ChronVac-C® vaccine delivered with Inovio's electroporation device; the 12-patient comparison group will receive standard-of-care treatment alone. The study has received approval from the Swedish Medical Products Agency and local ethical committee.
"If we can repeat the Phase I results in this phase IIb study there is certainly a possibility that vaccination with ChronVac-C® before drug therapy could become a part of the standard of care therapy for patients with chronic hepatitis C-virus infection. In particular, we hope that vaccination with this novel therapy will result in a considerable shortening of the duration of interferon and ribavirin treatment," said Anders Vahlne, CEO of ChronTech Pharma AB.
Dr. J. Joseph Kim, Inovio's president and CEO, said: "We are encouraged by the phase I results showing the improved cure rate in patients who received the HCV vaccine followed by a SOC drug therapy. Any improvement to the HCV standard of care response rates would be well-received by HCV patients and practitioners. We are pleased to collaborate in this advancement of ChronVac-C®, using Inovio's innovative delivery technology, into Phase II."
About Hepatitis C Virus
Hepatitis C virus (HCV) infection is the most common chronic blood borne infection in the United States, where approximately 3.5 million persons have been chronically infected. Worldwide, about 300 million people have been infected with HCV. Based on current statistics for hepatitis C, it is estimated that 8,000 to 10,000 people die each year from chronic liver disease caused by this condition. Chronic HCV infection is the leading indication for liver transplants in the United States. Total health costs associated with hepatitis C virus in the U.S. are estimated at more than $15 billion per year. No vaccine for HCV is currently available.
About Inovio's Electroporation-Based Delivery Technology
Inovio's electroporation-based DNA delivery systems can increase the cellular uptake of an agent by 1,000 times or more. When used to deliver DNA vaccines, Inovio's systems can increase levels of gene expression (i.e. production of the coded protein) and immune responses by 100 times or more compared to plasmid DNA delivered without other delivery enhancements. Inovio has recently reported best-in-class immune responses with DNA vaccines for cervical dysplasias/cancers and HIV. Inovio has also shown the safety and tolerability of its electroporation devices in many hundreds of patients and continues to advance device innovations to further enhance the utility of these devices for mass vaccinations.
About Inovio Pharmaceuticals, Inc.
Inovio is developing a new generation of vaccines, called DNA vaccines, to treat and prevent cancers and infectious diseases. These SynCon™ vaccines are designed to provide broad cross-strain protection against known as well as newly emergent strains of pathogens such as influenza. These vaccines, in combination with Inovio's proprietary electroporation delivery devices, have been shown to be safe and generate significant immune responses. Inovio's clinical programs include HPV/cervical dysplasia and cancer (therapeutic), avian flu (preventive), and HIV vaccines (both preventive and therapeutic). Inovio is developing universal influenza and other vaccines in collaboration with scientists from the University of Pennsylvania. Other partners and collaborators include Merck, National Cancer Institute, U.S. Military HIV Research Program, NIH, HIV Vaccines Trial Network, University of Southampton, and PATH Malaria Vaccine Initiative. More information is available at http://www.inovio.com/.
* * *
This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs (including, but not limited to, the fact that pre-clinical and clinical results referenced in this release may not be indicative of results achievable in other trials or for other indications, that the studies or trials may not be successful or achieve the results desired, that results from one study may not necessarily be reflected or supported by the results of other similar studies and that results from an animal study may not be indicative of results achievable in human studies), the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that the company and its collaborators hope to develop, evaluation of potential opportunities, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, our ability to successfully integrate Inovio and VGX Pharmaceuticals, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2009, our Form 10-Q for the nine months ended September 30, 2010, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.
CONTACTS:
Investors: Bernie Hertel, Inovio Pharmaceuticals 858-410-3101 bhertel@inovio.com
Media: Jeff Richardson, Richardson & Associates 805-491-8313 jeff@richardsonglobalpr.com
SOURCE Inovio Pharmaceuticals, Inc.
RELATED LINKS
http://www.inovio.com/
Source
Also See: An unusually high cure rate recorded after ChronVac-C® vaccination followed by standard treatment in patients with genotype 1 chronic hepatitis C
BLUE BELL, Pa., March 14, 2011 /PRNewswire/ -- Inovio Pharmaceuticals, Inc. (NYSE Amex: INO), a leader in the development of therapeutic and preventive vaccines against cancers and infectious diseases, announced today that its partner, ChronTech Pharma AB (formerly Tripep AB), has initiated a Phase IIb clinical study of its ChronVac-C® DNA vaccine for hepatitis C virus (HCV), delivered by Inovio's proprietary electroporation DNA vaccine delivery technology, in combination with standard of care.
In a Phase I clinical trial of ChronVac-C using Inovio's MedPulser® electroporation device the therapy resulted in a robust increase in T-cell immune responses against HCV and was safe and well-tolerated. Post-study observation of subjects who completed the protocol and then entered into standard of care (SOC) treatment using interferon and ribavirin showed a complete and rapid viral response (four weeks) in 70% of those participants (5 of 7 patients). More significantly, 83% of the participants (5 of 6 patients) who were monitored for an extended period of time, continued to be free of the virus six months after they completed SOC. SOC treatment alone usually results in about 40-50% of patients reaching undetectable virus levels after six months of treatment.
This Phase II follow-on trial is an open-label, single-dose, randomized trial of 32 patients to further explore the effect of the ChronVac-C® DNA vaccine administered by Inovio's MedPulser® electroporation delivery device. The therapy will be given two times, with four weeks in between, followed by SOC treatment after the final vaccine dose in treatment-naïve chronic HCV infected genotype-1 subjects. This trial will assess the level of immune responses, levels of HCV viral load, and further assess the response to the delivery technology. Twenty patients will receive ChronVac-C® vaccine delivered with Inovio's electroporation device; the 12-patient comparison group will receive standard-of-care treatment alone. The study has received approval from the Swedish Medical Products Agency and local ethical committee.
"If we can repeat the Phase I results in this phase IIb study there is certainly a possibility that vaccination with ChronVac-C® before drug therapy could become a part of the standard of care therapy for patients with chronic hepatitis C-virus infection. In particular, we hope that vaccination with this novel therapy will result in a considerable shortening of the duration of interferon and ribavirin treatment," said Anders Vahlne, CEO of ChronTech Pharma AB.
Dr. J. Joseph Kim, Inovio's president and CEO, said: "We are encouraged by the phase I results showing the improved cure rate in patients who received the HCV vaccine followed by a SOC drug therapy. Any improvement to the HCV standard of care response rates would be well-received by HCV patients and practitioners. We are pleased to collaborate in this advancement of ChronVac-C®, using Inovio's innovative delivery technology, into Phase II."
About Hepatitis C Virus
Hepatitis C virus (HCV) infection is the most common chronic blood borne infection in the United States, where approximately 3.5 million persons have been chronically infected. Worldwide, about 300 million people have been infected with HCV. Based on current statistics for hepatitis C, it is estimated that 8,000 to 10,000 people die each year from chronic liver disease caused by this condition. Chronic HCV infection is the leading indication for liver transplants in the United States. Total health costs associated with hepatitis C virus in the U.S. are estimated at more than $15 billion per year. No vaccine for HCV is currently available.
About Inovio's Electroporation-Based Delivery Technology
Inovio's electroporation-based DNA delivery systems can increase the cellular uptake of an agent by 1,000 times or more. When used to deliver DNA vaccines, Inovio's systems can increase levels of gene expression (i.e. production of the coded protein) and immune responses by 100 times or more compared to plasmid DNA delivered without other delivery enhancements. Inovio has recently reported best-in-class immune responses with DNA vaccines for cervical dysplasias/cancers and HIV. Inovio has also shown the safety and tolerability of its electroporation devices in many hundreds of patients and continues to advance device innovations to further enhance the utility of these devices for mass vaccinations.
About Inovio Pharmaceuticals, Inc.
Inovio is developing a new generation of vaccines, called DNA vaccines, to treat and prevent cancers and infectious diseases. These SynCon™ vaccines are designed to provide broad cross-strain protection against known as well as newly emergent strains of pathogens such as influenza. These vaccines, in combination with Inovio's proprietary electroporation delivery devices, have been shown to be safe and generate significant immune responses. Inovio's clinical programs include HPV/cervical dysplasia and cancer (therapeutic), avian flu (preventive), and HIV vaccines (both preventive and therapeutic). Inovio is developing universal influenza and other vaccines in collaboration with scientists from the University of Pennsylvania. Other partners and collaborators include Merck, National Cancer Institute, U.S. Military HIV Research Program, NIH, HIV Vaccines Trial Network, University of Southampton, and PATH Malaria Vaccine Initiative. More information is available at http://www.inovio.com/.
* * *
This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs (including, but not limited to, the fact that pre-clinical and clinical results referenced in this release may not be indicative of results achievable in other trials or for other indications, that the studies or trials may not be successful or achieve the results desired, that results from one study may not necessarily be reflected or supported by the results of other similar studies and that results from an animal study may not be indicative of results achievable in human studies), the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that the company and its collaborators hope to develop, evaluation of potential opportunities, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, our ability to successfully integrate Inovio and VGX Pharmaceuticals, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2009, our Form 10-Q for the nine months ended September 30, 2010, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.
CONTACTS:
Investors: Bernie Hertel, Inovio Pharmaceuticals 858-410-3101 bhertel@inovio.com
Media: Jeff Richardson, Richardson & Associates 805-491-8313 jeff@richardsonglobalpr.com
SOURCE Inovio Pharmaceuticals, Inc.
RELATED LINKS
http://www.inovio.com/
Source
Also See: An unusually high cure rate recorded after ChronVac-C® vaccination followed by standard treatment in patients with genotype 1 chronic hepatitis C
EASL schedules press conference and news briefings during International Liver Congress 2011
Published on March 14, 2011 at 10:22 AM
The EASL International Liver Congress is an opportunity for over 6,000 clinicians and scientists from around the world to hear the latest research, perspectives and treatments for liver diseases from principal experts in the field. It features a high-calibre and multi-disciplinary scientific programme covering groundbreaking information and in-depth examination of the most essential topics.
EASL will hold an international press conference and two morning news briefings during its International Liver Congress 2011 in Berlin.
EASL Press Conference
Date: Thursday 31st March 2011
Time: 11:00am - 12:00am
Location: Room 43
Leading experts will highlight new developments in the future management of viral hepatitis C. A question and answer session will follow the presentations.
Speakers will also be available for informal discussions and interviews following the presentations.
Due to limited space, please confirm your attendance at the press conference with the EASL press office now.
Morning News Briefings
To ensure you get the best out of ILC, news briefings will be held to provide you with the latest news and data on the following topics
Friday 1st April - Liver transplantation & Wilson's disease
Saturday 2nd April 2011 - Hepatocellular carcinoma & Fatty liver disease
Times: 8:00am - 8:45am
Location: The Press Centre
Onsite Press Office staff will be able to assist you in organising interviews with the relevant experts. Wi-Fi access will be available in the press working room.
• Abstracts can be viewed at: http://www1.easl.eu/easl2011/program/Orals/
• Details of the scientific programme are available at: http://www2.kenes.com/liver-congress/scientific/Pages/Timetable.aspx
• Stay up-to-date with all of the latest news and information, follow us @ILCpress!
Source: European Association for the Study of the Liver
Source
The EASL International Liver Congress is an opportunity for over 6,000 clinicians and scientists from around the world to hear the latest research, perspectives and treatments for liver diseases from principal experts in the field. It features a high-calibre and multi-disciplinary scientific programme covering groundbreaking information and in-depth examination of the most essential topics.
EASL will hold an international press conference and two morning news briefings during its International Liver Congress 2011 in Berlin.
EASL Press Conference
Date: Thursday 31st March 2011
Time: 11:00am - 12:00am
Location: Room 43
Leading experts will highlight new developments in the future management of viral hepatitis C. A question and answer session will follow the presentations.
Speakers will also be available for informal discussions and interviews following the presentations.
Due to limited space, please confirm your attendance at the press conference with the EASL press office now.
Morning News Briefings
To ensure you get the best out of ILC, news briefings will be held to provide you with the latest news and data on the following topics
Friday 1st April - Liver transplantation & Wilson's disease
Saturday 2nd April 2011 - Hepatocellular carcinoma & Fatty liver disease
Times: 8:00am - 8:45am
Location: The Press Centre
Onsite Press Office staff will be able to assist you in organising interviews with the relevant experts. Wi-Fi access will be available in the press working room.
• Abstracts can be viewed at: http://www1.easl.eu/easl2011/program/Orals/
• Details of the scientific programme are available at: http://www2.kenes.com/liver-congress/scientific/Pages/Timetable.aspx
• Stay up-to-date with all of the latest news and information, follow us @ILCpress!
Source: European Association for the Study of the Liver
Source
March 12, 2011
Lack of health insurance limits hepatitis C patients' access to latest antiviral therapy
Public release date: 24-Feb-2011
Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell
High costs, insurance status, and eligibility issues restrict treatment options
New research has determined that patients in the U.S. with hepatitis C virus (HCV) are twice as likely to not have health insurance coverage compared with those without the disease. In fact researchers found only a third of HCV infected Americans have access to antiviral therapy; the remaining are either uninsured or not candidates for therapy due to treatment contraindications. Details of this study are published in the March issue of Hepatology, a peer-reviewed journal of the American Association for the Study of Liver Diseases (AASLD).
HCV is the most common cause of chronic liver disease, hepatocellular (liver) cancer, and liver transplantation in the U.S., with up to 85% of HCV-positive individuals (3.5 million) developing chronic HCV infection. Symptoms of chronic HCV are non-specific which can inhibit diagnosis and as many as 75% of patients are unaware of their HCV infection (Hagan et al., 2006). Furthermore, the Centers for Disease Control and Prevention (CDC) estimates that HCV causes 12,000 deaths in the U.S. each year.
"Successful treatment with antiviral therapy improves health-related quality of life in patients with HCV and could potentially reduce morbidity and mortality in patients," said Zobair Younossi, MD, MPH, from the Center of Liver Diseases at Inova Fairfax Hospital in Virginia and lead author of the study. "A significant number of HCV patients, however, may not even have access to antiviral therapy due to lack of adequate health insurance coverage." It is estimated to cost up to $48,000 per year for monitoring and treatment of HCV.
For the current study, researchers analyzed health insurance status and treatment candidacy of HCV-positive individuals using 2005-2008 data collected from the National Health and Nutritional Examination Survey (NHANES). This information was collected via household interviews, physical examinations and extensive laboratory sample data from subjects who were 18 years of age or older and living in the U.S.
Analysis showed that 1.16% of study subjects were infected with HCV. Among those with HCV only 61% were insured compared to 81% of HCV-negative individuals. HCV infection was an independent predictor of being uninsured even after adjusting for demographic disparity in the HCV-positive group. Approximately 67% of HCV-positive patients were eligible for treatment, however only 54% of those treatment candidates had insurance coverage.
Some individuals with HCV may not be eligible for antiviral therapy due to contraindications to treatment. Previous studies have found that only half of HCV patients exhibit a positive response to peginterferon/ribavirin treatment. "The side effect profile of the current antiviral therapy requires careful selection of treatment candidates with a number of chronic conditions," said Dr. Younossi. The authors noted that patients with comorbidities such as active cardiac disease, severe depression, or renal failure are typically ineligible for antiviral therapy due to severe adverse events that may occur with treatment.
Research showed that only 36% of HCV-positive patients who were eligible for antiviral therapy had health insurance. "Access to care for HCV patients is critical. Our results have important implications for HCV-infected patients and should be considered as new health care reform legislation takes effect," Dr. Younossi concluded.
###
Article: "Insurance Status and Treatment Candidacy of Hepatitis C Patients: Analysis of Population-based Data from the United States." Maria Stepanova, Fasiha Kanwal, Hashem B. El-Serag, Zobair M. Younossi. Hepatology; Published Online: February 11, 2011 (DOI: 10.1002/hep.24131); Print Issue Date: March 2011. http://onlinelibrary.wiley.com/doi/10.1002/hep.24131/abstract.
This study is published in Hepatology. Media wishing to receive a PDF of the articles may contact healthnews@wiley.com.
About the Journal
Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-3350.
About Wiley-Blackwell
Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit http://www.wileyblackwell.com/ or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.
Source
Also See: Many Hepatitis C-Positive Patients Are Uninsured
Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell
High costs, insurance status, and eligibility issues restrict treatment options
New research has determined that patients in the U.S. with hepatitis C virus (HCV) are twice as likely to not have health insurance coverage compared with those without the disease. In fact researchers found only a third of HCV infected Americans have access to antiviral therapy; the remaining are either uninsured or not candidates for therapy due to treatment contraindications. Details of this study are published in the March issue of Hepatology, a peer-reviewed journal of the American Association for the Study of Liver Diseases (AASLD).
HCV is the most common cause of chronic liver disease, hepatocellular (liver) cancer, and liver transplantation in the U.S., with up to 85% of HCV-positive individuals (3.5 million) developing chronic HCV infection. Symptoms of chronic HCV are non-specific which can inhibit diagnosis and as many as 75% of patients are unaware of their HCV infection (Hagan et al., 2006). Furthermore, the Centers for Disease Control and Prevention (CDC) estimates that HCV causes 12,000 deaths in the U.S. each year.
"Successful treatment with antiviral therapy improves health-related quality of life in patients with HCV and could potentially reduce morbidity and mortality in patients," said Zobair Younossi, MD, MPH, from the Center of Liver Diseases at Inova Fairfax Hospital in Virginia and lead author of the study. "A significant number of HCV patients, however, may not even have access to antiviral therapy due to lack of adequate health insurance coverage." It is estimated to cost up to $48,000 per year for monitoring and treatment of HCV.
For the current study, researchers analyzed health insurance status and treatment candidacy of HCV-positive individuals using 2005-2008 data collected from the National Health and Nutritional Examination Survey (NHANES). This information was collected via household interviews, physical examinations and extensive laboratory sample data from subjects who were 18 years of age or older and living in the U.S.
Analysis showed that 1.16% of study subjects were infected with HCV. Among those with HCV only 61% were insured compared to 81% of HCV-negative individuals. HCV infection was an independent predictor of being uninsured even after adjusting for demographic disparity in the HCV-positive group. Approximately 67% of HCV-positive patients were eligible for treatment, however only 54% of those treatment candidates had insurance coverage.
Some individuals with HCV may not be eligible for antiviral therapy due to contraindications to treatment. Previous studies have found that only half of HCV patients exhibit a positive response to peginterferon/ribavirin treatment. "The side effect profile of the current antiviral therapy requires careful selection of treatment candidates with a number of chronic conditions," said Dr. Younossi. The authors noted that patients with comorbidities such as active cardiac disease, severe depression, or renal failure are typically ineligible for antiviral therapy due to severe adverse events that may occur with treatment.
Research showed that only 36% of HCV-positive patients who were eligible for antiviral therapy had health insurance. "Access to care for HCV patients is critical. Our results have important implications for HCV-infected patients and should be considered as new health care reform legislation takes effect," Dr. Younossi concluded.
###
Article: "Insurance Status and Treatment Candidacy of Hepatitis C Patients: Analysis of Population-based Data from the United States." Maria Stepanova, Fasiha Kanwal, Hashem B. El-Serag, Zobair M. Younossi. Hepatology; Published Online: February 11, 2011 (DOI: 10.1002/hep.24131); Print Issue Date: March 2011. http://onlinelibrary.wiley.com/doi/10.1002/hep.24131/abstract.
This study is published in Hepatology. Media wishing to receive a PDF of the articles may contact healthnews@wiley.com.
About the Journal
Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-3350.
About Wiley-Blackwell
Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit http://www.wileyblackwell.com/ or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.
Source
Also See: Many Hepatitis C-Positive Patients Are Uninsured
Treatment failure and resistance with direct acting antiviral drugs against hepatitis C virus
Hepatology. 2011 Mar 3. doi: 10.1002/hep.24262. [Epub ahead of print]
Pawlotsky JM.
National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM U955, Créteil, France. jean-michel.pawlotsky@hmn.aphp.fr.
Abstract
Current treatment of chronic hepatitis C virus infection is based on the combination of pegylated interferon-α and ribavirin. The recent development of direct-acting antiviral molecules active on hepatitis C virus, together with in vitro and in vivo studies showing that these drugs may lead to the selection of resistant viruses if administered alone, has raised concerns that resistance may undermine therapy based on direct acting antivirals. A new standard-of-care treatment will soon be available for both treatment-naïve and -experienced patients infected with hepatitis C virus genotype 1, based on a triple combination of pegylated interferon-α, ribavirin and a protease inhibitor, either telaprevir or boceprevir. With this therapy, most failures to eradicate infection in treatment-adherent patients are due to an inadequate response to pegylated interferon-α and ribavirin, in the context of a low genetic barrier to resistance of first-generation protease inhibitors. This article reviews patterns of resistance to hepatitis C virus direct acting antiviral drugs in development, the mechanisms underlying treatment failure when these drugs are combined with pegylated interferon-α and ribavirin, the consequences of treatment failure, and possible means of optimizing therapies using direct acting antivirals in the future. (HEPATOLOGY 2011.).
Copyright © 2011 American Association for the Study of Liver Diseases.
PMID: 21374691 [PubMed - as supplied by publisher]
Source
Pawlotsky JM.
National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM U955, Créteil, France. jean-michel.pawlotsky@hmn.aphp.fr.
Abstract
Current treatment of chronic hepatitis C virus infection is based on the combination of pegylated interferon-α and ribavirin. The recent development of direct-acting antiviral molecules active on hepatitis C virus, together with in vitro and in vivo studies showing that these drugs may lead to the selection of resistant viruses if administered alone, has raised concerns that resistance may undermine therapy based on direct acting antivirals. A new standard-of-care treatment will soon be available for both treatment-naïve and -experienced patients infected with hepatitis C virus genotype 1, based on a triple combination of pegylated interferon-α, ribavirin and a protease inhibitor, either telaprevir or boceprevir. With this therapy, most failures to eradicate infection in treatment-adherent patients are due to an inadequate response to pegylated interferon-α and ribavirin, in the context of a low genetic barrier to resistance of first-generation protease inhibitors. This article reviews patterns of resistance to hepatitis C virus direct acting antiviral drugs in development, the mechanisms underlying treatment failure when these drugs are combined with pegylated interferon-α and ribavirin, the consequences of treatment failure, and possible means of optimizing therapies using direct acting antivirals in the future. (HEPATOLOGY 2011.).
Copyright © 2011 American Association for the Study of Liver Diseases.
PMID: 21374691 [PubMed - as supplied by publisher]
Source
Second phase HCV RNA decline during telaprevir based therapy increases with drug effectiveness: Implications for treatment duration
Hepatology. 2011 Mar 7. doi: 10.1002/hep.24272. [Epub ahead of print]
Guedj J, Perelson AS.
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos 87545, USA.
Abstract
Hepatitis C virus (HCV) RNA decay during antiviral therapy is characterized by a rapid first phase followed by a slower second phase. The current understanding of viral kinetics attributes the magnitude of the first phase decay to the treatment effectiveness, whereas the second phase decay is attributed to the progressive loss of infected cells. Here we analyzed data from 44 patients treated with telaprevir, a potent HCV protease inhibitor. Using a viral kinetic model that accounts for the pharmacokinetics of telaprevir, we found that the second phase slope of viral decline to be strongly correlated with the treatment effectiveness and to be roughly four-fold more rapid than has been reported with interferon-based therapies. Since telaprevir is not known to increase the death rate of infected cells, our results suggest the second phase slope of viral decline is driven not only by the death of infected cells but may also involve other mechanisms, such as a treatment effectiveness-dependent degradation of intracellular viral RNA. As a consequence of the enhanced viral decay caused by the high antiviral effectiveness of telaprevir, we predict that if drug resistance could be avoided by using an appropriate combination of antiviral agents, treatment duration needed to clear HCV might be dramatically shortened. Indeed, we predict that in 95% of fully compliant patients, the last virus particle should be eliminated by week 7 of therapy. If the remaining infected hepatocytes act as a potential reservoir for the renewal of infection, no more than 10 weeks of treatment should be sufficient to clear the infection in 95% of fully compliant patients. However, if patients miss doses, treatment duration would need to be extended. (HEPATOLOGY 2011.).
Copyright © 2011 American Association for the Study of Liver Diseases.
PMID: 21384401 [PubMed - as supplied by publisher]
Source
Guedj J, Perelson AS.
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos 87545, USA.
Abstract
Hepatitis C virus (HCV) RNA decay during antiviral therapy is characterized by a rapid first phase followed by a slower second phase. The current understanding of viral kinetics attributes the magnitude of the first phase decay to the treatment effectiveness, whereas the second phase decay is attributed to the progressive loss of infected cells. Here we analyzed data from 44 patients treated with telaprevir, a potent HCV protease inhibitor. Using a viral kinetic model that accounts for the pharmacokinetics of telaprevir, we found that the second phase slope of viral decline to be strongly correlated with the treatment effectiveness and to be roughly four-fold more rapid than has been reported with interferon-based therapies. Since telaprevir is not known to increase the death rate of infected cells, our results suggest the second phase slope of viral decline is driven not only by the death of infected cells but may also involve other mechanisms, such as a treatment effectiveness-dependent degradation of intracellular viral RNA. As a consequence of the enhanced viral decay caused by the high antiviral effectiveness of telaprevir, we predict that if drug resistance could be avoided by using an appropriate combination of antiviral agents, treatment duration needed to clear HCV might be dramatically shortened. Indeed, we predict that in 95% of fully compliant patients, the last virus particle should be eliminated by week 7 of therapy. If the remaining infected hepatocytes act as a potential reservoir for the renewal of infection, no more than 10 weeks of treatment should be sufficient to clear the infection in 95% of fully compliant patients. However, if patients miss doses, treatment duration would need to be extended. (HEPATOLOGY 2011.).
Copyright © 2011 American Association for the Study of Liver Diseases.
PMID: 21384401 [PubMed - as supplied by publisher]
Source
March 11, 2011
Inhibitex Reports Fourth Quarter and Calendar Year 2010 Financial Results and Corporate Highlights
March 11, 2011 07:00 AM Eastern Time
Conference Call Today at 9:00 a.m. EST
ATLANTA--(BUSINESS WIRE)--Inhibitex, Inc. (NASDAQ:INHX) today announced its financial results for the fourth quarter and year ended December 31, 2010, and provided an update on recent clinical and corporate developments.
“We are very pleased with the progress we have made over the past year in advancing our antiviral pipeline, which culminated in establishing clinical proof of concept for both FV-100, which we are developing to treat shingles, and more recently, INX-189, which we are developing to treat chronic infections caused by hepatitis C virus,” stated Russell H. Plumb, President and CEO of Inhibitex, Inc. “Looking ahead in 2011, we expect to complete our Phase 1b trial of INX-189 in the near-term and are developing plans to further evaluate its safety and antiviral activity in a Phase 2 program that we estimate could begin in the third quarter of 2011. Further, over the next several months we anticipate completing our evaluation of the potential clinical and regulatory pathways and commercial opportunities for FV-100, and look forward to determining the possible next steps in its development.”
Clinical Development Highlights
• INX-189: Earlier this quarter, the Company announced favorable interim results from a Phase 1b study of INX-189 in HCV genotype 1 patients where INX-189, its nucleotide polymerase inhibitor, demonstrated a clinically meaningful antiviral effect (>1 log10 IU/mL reduction in baseline viral load) in seven days of monotherapy at a relatively low (25mg) once-daily dose.
• FV-100: In December 2010, the Company successfully completed a first-in-patient, Phase 2 clinical trial in shingles patients where a once-daily dose of 400mg FV-100 demonstrated the potential to reduce both the sub-acute pain and the incidence of post herpetic neuralgia (PHN) associated with shingles infections.
Fourth Quarter 2010 Financial Results
As of December 31, 2010, the Company held $19.6 million in cash, cash equivalents and short-term investments.
The Company reported a net loss for the fourth quarter of 2010 of $7.0 million, as compared to a net loss of $4.7 million in the fourth quarter of 2009. The $2.3 million increase in net loss in the fourth quarter of 2010 was primarily the result of higher research and development expense, and to a lesser extent, higher general and administrative expense and lower net interest income, offset in part by an increase in other income. Basic and diluted net loss per share was $0.11 for the fourth quarter of 2010 compared to $0.08 for the fourth quarter of 2009. The increase in net loss per share in the fourth quarter of 2010, as compared to the fourth quarter of 2009, was due to the higher net loss, offset in part by an increase in the weighted average number of shares outstanding.
Research and development expense increased to $6.6 million in the fourth quarter of 2010 from $4.3 million in the fourth quarter of 2009. This $2.3 million increase was primarily due to a $1.7 million increase in direct costs incurred in connection with the initiation of a Phase 1b clinical trial of INX-189 in November of 2010 and to a lesser extent, the completion of a Phase 2 clinical trial of FV-100 in the December of 2010, as well as an increase of $0.6 million in non-direct expenses associated with higher consulting and professional fees and compensation and share-based compensation expense.
General and administrative expense increased to $1.2 million in the fourth quarter of 2010 from $0.7 million in the fourth quarter of 2009. The increase of $0.5 million was primarily the result of an increase in legal and professional fees and compensation and share-based compensation expense.
Other income increased to $0.5 million in the fourth quarter of 2010 from zero in the fourth quarter of 2009 due to the receipt of $0.5 million Therapeutic Tax Credit grant in the fourth quarter of 2010 that was not received in 2009.
Year End 2010 Financial Results
For the year ended December 31, 2010, the Company reported a net loss of $22.7 million, as compared to $17.6 million for 2009. Basic and diluted net loss per share for the year ended December 31, 2010, was $0.37, as compared to $0.38 for 2009. The $5.1 million increase in net loss in 2010 was primarily the result of higher research and development expense associated with a Phase 2 clinical trial of FV-100, the initiation of a Phase 1 clinical program for INX-189 in mid-2010 and an increase in other non-direct research and development costs, as well as higher general and administrative expense and lower net interest income, offset in part by higher revenues from a collaborative license and development agreement and net other income. The slight decrease in net loss per share in 2010 was due to an increase in the weighted average number of shares outstanding, offset by the higher net loss.
Revenue increased to $1.9 million in 2010 from $1.2 million in 2009 due to the receipt of a $0.7 million milestone payment in the first quarter of 2010 that did not occur in 2009.
Research and development expense increased to $21.0 million in 2010 from $15.4 million in 2009, primarily due to a $4.9 million increase in direct costs incurred in connection with a Phase 2 clinical trial of FV-100 that was conducted throughout 2010 and the initiation of a Phase 1 clinical program of INX-189 in mid-2010, as well as an increase of $0.7 million in non-direct expenses associated with higher consulting and professional fees and compensation and share-based compensation expense.
General and administrative expense increased to $4.1 million in 2010 from $3.6 million in 2009. The increase of $0.5 million was primarily the result of an increase in legal and professional fees and compensation and share-based compensation expense incurred in the fourth quarter of 2010.
Other income increased to $0.5 million in 2010 from zero in 2009 due to the receipt of $0.5 million Therapeutic Tax Credit grant in the fourth quarter of 2010 that was not received in 2009.
Recent Corporate Developments
INX-189 for Chronic Hepatitis C – In January 2011, the Company reported favorable preliminary interim safety and antiviral data from the first two monotherapy cohorts of its ongoing Phase 1b clinical trial of INX-189. The Company reported that INX-189, dosed once-daily at 9mg and 25mg for seven days, demonstrated potent antiviral activity with a mean HCV RNA reduction from baseline levels of -0.71 and -1.03 log10 IU/mL, respectively. In addition to the mean reductions in viral load, clinically meaningful decreases in alanine transaminase (ALT) levels were observed for patients receiving INX-189 at both dose levels, and no patients experienced viral breakthrough. There were no serious adverse events reported, no discontinuations due to an adverse event, and no adverse events related to changes in clinical laboratory evaluations. All reported adverse events were mild or moderate and were not dose dependent. In addition, the pharmacokinetics of the 9mg and 25mg doses in HCV-infected patients were comparable to those observed in healthy volunteers.
The Phase 1b trial, which is being conducted under an IND in the United States, is a double-blind, placebo-controlled, dose escalation study designed to evaluate the safety, tolerability, pharmacokinetics and antiviral activity of INX-189, administered orally once-daily for seven days in HCV genotype 1 treatment-naïve patients. Each treatment cohort in the trial is comprised of 10 patients, eight that receive INX-189 and two that receive placebo. In addition to the 9mg and 25mg dose cohorts, the Company will enroll three more INX-189 monotherapy cohorts in the trial, including a recently-added 100mg cohort, as well as two cohorts that will receive 9mg and 25mg of INX-189 once daily for seven days in combination with ribavirin. The Company anticipates completing this ongoing Phase 1b trial around the end of the first quarter of 2011.
In February 2011, the Company reported that the U.S. Food and Drug Administration (FDA) designated the investigation of INX-189 as a Fast Track development program. Fast Track programs are designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life threatening conditions and that demonstrate the potential to address unmet medical needs.
FV-100 for Shingles – In December 2010, the Company reported top-line safety and efficacy data from its Phase 2 clinical trial of FV-100, an oral antiviral compound being developed to treat shingles, including the reduction of shingles-associated pain and the incidence of PHN. The study included 350 shingles patients and compared two once-daily doses of FV-100 (200mg and 400mg) to valacyclovir, one of the most commonly-used antiviral drugs to treat shingles. Valacyclovir was administered three times per day at 1,000 mg per dose.
Numerically favorable treatment differences were observed for both doses of FV-100 as compared to valacyclovir for the primary endpoint of the study, defined as the reduction in the severity and duration of shingles-associated acute pain over the first 30 days, or the Burden of Illness (BOI30 AUC), although these treatment differences were not statistically significant. There were also numerically favorable treatment differences observed for key secondary pain endpoints, including a 14% relative reduction in the severity and duration of shingles-associated pain over 90 days (BOI90 AUC) and a 39% relative reduction in the incidence of PHN for the 400mg dose of FV-100. The trial was not powered to demonstrate statistically significant treatment differences between the arms with respect to these and other secondary endpoints. FV-100 was generally well tolerated at both dose levels, and demonstrated a similar adverse event profile as compared to valacyclovir. All three treatment arms showed a relatively low proportion of adverse and serious adverse events. The Company is currently performing various analyses of the full Phase 2 data set and an evaluation of various clinical, regulatory and commercial pathways for the potential future development of FV-100, which it anticipates concluding in the first half of 2011.
Conference Call and Webcast Information
Russell H. Plumb, President and Chief Executive Officer of Inhibitex, and other members of management will review the Company’s fourth quarter and year-end 2010 operating results and financial position, as well as provide a general update on the Company via a webcast and conference call today at 9:00 a.m. EST. To access the conference call, dial (877) 407-9210 (domestic) or (201) 689-8049 (international). A replay of the call will be available from 11:00 a.m. EST on March 11 until April 11, 2011, at midnight. To access the replay, please dial (877) 660-6853 (domestic) or (201) 612-7415 (international) and reference the account # 286 and the conference ID # 366809. A live audio webcast of the call and the archived webcast will be available under the News and Events category on the Inhibitex website at http://www.inhibitex.com/.
About HCV and INX-189
Chronic hepatitis C is a disease of the liver caused by HCV, which can result in cirrhosis and cancer, and is the leading reason for liver transplants in the United States. Inhibitex is developing a series of proprietary nucleotide inhibitors, referred to as protides, which target and inhibit the RNA-dependent RNA polymerase (NS5b) of HCV. The Company believes that, based on in vitro data, INX-189 is one of the most potent HCV nucleotide polymerase inhibitor currently in clinical development, and that results from preclinical studies and its Phase 1 trials of INX-189 to-date support its potential as a once-daily oral antiviral therapy amenable to fixed-dose combination with other antivirals for the treatment of patients with chronic hepatitis C infections.
About Shingles and FV-100
The Company is developing FV-100 to treat herpes zoster, also commonly referred to as shingles, which is an infection caused by the reactivation of varicella zoster virus (“VZV”), the same virus that causes chicken pox. Published in vitro studies have demonstrated that FV-100, an orally available bicyclic nucleoside analogue, is significantly more potent against VZV and can inhibit its replication substantially faster than any other antiviral agent currently approved for the treatment of shingles. Inhibitex believes these characteristics, a favorable pharmacokinetic profile, and the results of a recently-completed Phase 2 trial support the potential of FV-100 as a once-daily oral therapy to reduce the incidence, severity and duration of shingles-associated pain and PHN.
About Inhibitex
Inhibitex, Inc. is a biopharmaceutical company focused on developing products to treat and prevent serious infectious diseases. In addition to its two clinical-stage programs, INX-189 and FV-100, the Company’s pipeline includes other HCV nucleotide inhibitors in preclinical development. It has also licensed its proprietary MSCRAMM® protein platform to Pfizer for its use in the development of a staphylococcal vaccine, which is currently being evaluated in Phase 1 clinical trials.
For additional information about the Company, please visit http://www.inhibitex.com/
Safe Harbor Statement
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than historical facts included in this press release, including statements regarding: the anticipated time it will take the Company to conclude its assessment of the FV-100 Phase 2 data and the compound’s potential clinical, regulatory and commercial pathways; the potential for FV-100 to be dosed once daily and reduce the incidence, severity and duration of shingles-associated pain and PHN; the Company plans to enroll additional cohorts in the ongoing Phase 1b trial of INX-189; the time frame in which a Phase 2 clinical program of INX-189 can be initiated; the Company’s belief that INX-189 is one of the most potent HCV nucleotide polymerase inhibitor currently in clinical development; the results of preclinical studies and the Phase 1 trials of INX-189 to-date supporting its potential as a once-daily oral antiviral amenable to fixed dose combination with other antivirals; and the anticipated time when the ongoing Phase 1b trial of INX-189 will be completed, are forward looking statements. These intentions, expectations, or results may not be achieved in the future and various important factors could cause actual results or events to differ materially from the forward-looking statements that the Company makes, including the risk of: the Company, the FDA, a data safety monitoring board, or an institutional review board (IRB) delaying, suspending or terminating the clinical development of FV-100 or INX-189 at any time for a lack of safety, tolerability, antiviral activity, commercial viability, or any other reason; FV-100 not demonstrating sufficient activity or potential in reducing the incidence and severity of shingles-related pain and PHN, to be clinically relevant or commercially viable; the Company or its clinical investigators not being able to enroll additional HCV patients in the Phase 1b trial on a timely basis; obtaining, maintaining and protecting the intellectual property incorporated into and supporting the commercial viability of the Company’s product candidates; and other cautionary statements contained elsewhere herein and in its Annual Report on Form 10-K for the year ended December 31, 2009, as filed with the Securities and Exchange Commission, or SEC, on March 26, 2010, and its Quarterly Reports on Form 10-Q for the quarter ended March 31, 2010, June 30, 2010, and September 30, 2010, as filed with the SEC on May 13, 2010, August 12, 2010, and November 15, 2010, respectively. Given these uncertainties, you should not place undue reliance on these forward-looking statements, which apply only as of the date of this press release.
There may be events in the future that the Company is unable to predict accurately, or over which it has no control. The Company's business, financial condition, results of operations and prospects may change. The Company may not update these forward-looking statements, even though its situation may change in the future, unless it has obligations under the Federal securities laws to update and disclose material developments related to previously disclosed information. The Company qualifies all of the information contained in this press release, and particularly its forward-looking statements, by these cautionary statements.
Inhibitex® and MSCRAMM® are registered trademarks of Inhibitex, Inc.
Source
Conference Call Today at 9:00 a.m. EST
ATLANTA--(BUSINESS WIRE)--Inhibitex, Inc. (NASDAQ:INHX) today announced its financial results for the fourth quarter and year ended December 31, 2010, and provided an update on recent clinical and corporate developments.
“We are very pleased with the progress we have made over the past year in advancing our antiviral pipeline, which culminated in establishing clinical proof of concept for both FV-100, which we are developing to treat shingles, and more recently, INX-189, which we are developing to treat chronic infections caused by hepatitis C virus,” stated Russell H. Plumb, President and CEO of Inhibitex, Inc. “Looking ahead in 2011, we expect to complete our Phase 1b trial of INX-189 in the near-term and are developing plans to further evaluate its safety and antiviral activity in a Phase 2 program that we estimate could begin in the third quarter of 2011. Further, over the next several months we anticipate completing our evaluation of the potential clinical and regulatory pathways and commercial opportunities for FV-100, and look forward to determining the possible next steps in its development.”
Clinical Development Highlights
• INX-189: Earlier this quarter, the Company announced favorable interim results from a Phase 1b study of INX-189 in HCV genotype 1 patients where INX-189, its nucleotide polymerase inhibitor, demonstrated a clinically meaningful antiviral effect (>1 log10 IU/mL reduction in baseline viral load) in seven days of monotherapy at a relatively low (25mg) once-daily dose.
• FV-100: In December 2010, the Company successfully completed a first-in-patient, Phase 2 clinical trial in shingles patients where a once-daily dose of 400mg FV-100 demonstrated the potential to reduce both the sub-acute pain and the incidence of post herpetic neuralgia (PHN) associated with shingles infections.
Fourth Quarter 2010 Financial Results
As of December 31, 2010, the Company held $19.6 million in cash, cash equivalents and short-term investments.
The Company reported a net loss for the fourth quarter of 2010 of $7.0 million, as compared to a net loss of $4.7 million in the fourth quarter of 2009. The $2.3 million increase in net loss in the fourth quarter of 2010 was primarily the result of higher research and development expense, and to a lesser extent, higher general and administrative expense and lower net interest income, offset in part by an increase in other income. Basic and diluted net loss per share was $0.11 for the fourth quarter of 2010 compared to $0.08 for the fourth quarter of 2009. The increase in net loss per share in the fourth quarter of 2010, as compared to the fourth quarter of 2009, was due to the higher net loss, offset in part by an increase in the weighted average number of shares outstanding.
Research and development expense increased to $6.6 million in the fourth quarter of 2010 from $4.3 million in the fourth quarter of 2009. This $2.3 million increase was primarily due to a $1.7 million increase in direct costs incurred in connection with the initiation of a Phase 1b clinical trial of INX-189 in November of 2010 and to a lesser extent, the completion of a Phase 2 clinical trial of FV-100 in the December of 2010, as well as an increase of $0.6 million in non-direct expenses associated with higher consulting and professional fees and compensation and share-based compensation expense.
General and administrative expense increased to $1.2 million in the fourth quarter of 2010 from $0.7 million in the fourth quarter of 2009. The increase of $0.5 million was primarily the result of an increase in legal and professional fees and compensation and share-based compensation expense.
Other income increased to $0.5 million in the fourth quarter of 2010 from zero in the fourth quarter of 2009 due to the receipt of $0.5 million Therapeutic Tax Credit grant in the fourth quarter of 2010 that was not received in 2009.
Year End 2010 Financial Results
For the year ended December 31, 2010, the Company reported a net loss of $22.7 million, as compared to $17.6 million for 2009. Basic and diluted net loss per share for the year ended December 31, 2010, was $0.37, as compared to $0.38 for 2009. The $5.1 million increase in net loss in 2010 was primarily the result of higher research and development expense associated with a Phase 2 clinical trial of FV-100, the initiation of a Phase 1 clinical program for INX-189 in mid-2010 and an increase in other non-direct research and development costs, as well as higher general and administrative expense and lower net interest income, offset in part by higher revenues from a collaborative license and development agreement and net other income. The slight decrease in net loss per share in 2010 was due to an increase in the weighted average number of shares outstanding, offset by the higher net loss.
Revenue increased to $1.9 million in 2010 from $1.2 million in 2009 due to the receipt of a $0.7 million milestone payment in the first quarter of 2010 that did not occur in 2009.
Research and development expense increased to $21.0 million in 2010 from $15.4 million in 2009, primarily due to a $4.9 million increase in direct costs incurred in connection with a Phase 2 clinical trial of FV-100 that was conducted throughout 2010 and the initiation of a Phase 1 clinical program of INX-189 in mid-2010, as well as an increase of $0.7 million in non-direct expenses associated with higher consulting and professional fees and compensation and share-based compensation expense.
General and administrative expense increased to $4.1 million in 2010 from $3.6 million in 2009. The increase of $0.5 million was primarily the result of an increase in legal and professional fees and compensation and share-based compensation expense incurred in the fourth quarter of 2010.
Other income increased to $0.5 million in 2010 from zero in 2009 due to the receipt of $0.5 million Therapeutic Tax Credit grant in the fourth quarter of 2010 that was not received in 2009.
Recent Corporate Developments
INX-189 for Chronic Hepatitis C – In January 2011, the Company reported favorable preliminary interim safety and antiviral data from the first two monotherapy cohorts of its ongoing Phase 1b clinical trial of INX-189. The Company reported that INX-189, dosed once-daily at 9mg and 25mg for seven days, demonstrated potent antiviral activity with a mean HCV RNA reduction from baseline levels of -0.71 and -1.03 log10 IU/mL, respectively. In addition to the mean reductions in viral load, clinically meaningful decreases in alanine transaminase (ALT) levels were observed for patients receiving INX-189 at both dose levels, and no patients experienced viral breakthrough. There were no serious adverse events reported, no discontinuations due to an adverse event, and no adverse events related to changes in clinical laboratory evaluations. All reported adverse events were mild or moderate and were not dose dependent. In addition, the pharmacokinetics of the 9mg and 25mg doses in HCV-infected patients were comparable to those observed in healthy volunteers.
The Phase 1b trial, which is being conducted under an IND in the United States, is a double-blind, placebo-controlled, dose escalation study designed to evaluate the safety, tolerability, pharmacokinetics and antiviral activity of INX-189, administered orally once-daily for seven days in HCV genotype 1 treatment-naïve patients. Each treatment cohort in the trial is comprised of 10 patients, eight that receive INX-189 and two that receive placebo. In addition to the 9mg and 25mg dose cohorts, the Company will enroll three more INX-189 monotherapy cohorts in the trial, including a recently-added 100mg cohort, as well as two cohorts that will receive 9mg and 25mg of INX-189 once daily for seven days in combination with ribavirin. The Company anticipates completing this ongoing Phase 1b trial around the end of the first quarter of 2011.
In February 2011, the Company reported that the U.S. Food and Drug Administration (FDA) designated the investigation of INX-189 as a Fast Track development program. Fast Track programs are designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life threatening conditions and that demonstrate the potential to address unmet medical needs.
FV-100 for Shingles – In December 2010, the Company reported top-line safety and efficacy data from its Phase 2 clinical trial of FV-100, an oral antiviral compound being developed to treat shingles, including the reduction of shingles-associated pain and the incidence of PHN. The study included 350 shingles patients and compared two once-daily doses of FV-100 (200mg and 400mg) to valacyclovir, one of the most commonly-used antiviral drugs to treat shingles. Valacyclovir was administered three times per day at 1,000 mg per dose.
Numerically favorable treatment differences were observed for both doses of FV-100 as compared to valacyclovir for the primary endpoint of the study, defined as the reduction in the severity and duration of shingles-associated acute pain over the first 30 days, or the Burden of Illness (BOI30 AUC), although these treatment differences were not statistically significant. There were also numerically favorable treatment differences observed for key secondary pain endpoints, including a 14% relative reduction in the severity and duration of shingles-associated pain over 90 days (BOI90 AUC) and a 39% relative reduction in the incidence of PHN for the 400mg dose of FV-100. The trial was not powered to demonstrate statistically significant treatment differences between the arms with respect to these and other secondary endpoints. FV-100 was generally well tolerated at both dose levels, and demonstrated a similar adverse event profile as compared to valacyclovir. All three treatment arms showed a relatively low proportion of adverse and serious adverse events. The Company is currently performing various analyses of the full Phase 2 data set and an evaluation of various clinical, regulatory and commercial pathways for the potential future development of FV-100, which it anticipates concluding in the first half of 2011.
Conference Call and Webcast Information
Russell H. Plumb, President and Chief Executive Officer of Inhibitex, and other members of management will review the Company’s fourth quarter and year-end 2010 operating results and financial position, as well as provide a general update on the Company via a webcast and conference call today at 9:00 a.m. EST. To access the conference call, dial (877) 407-9210 (domestic) or (201) 689-8049 (international). A replay of the call will be available from 11:00 a.m. EST on March 11 until April 11, 2011, at midnight. To access the replay, please dial (877) 660-6853 (domestic) or (201) 612-7415 (international) and reference the account # 286 and the conference ID # 366809. A live audio webcast of the call and the archived webcast will be available under the News and Events category on the Inhibitex website at http://www.inhibitex.com/.
About HCV and INX-189
Chronic hepatitis C is a disease of the liver caused by HCV, which can result in cirrhosis and cancer, and is the leading reason for liver transplants in the United States. Inhibitex is developing a series of proprietary nucleotide inhibitors, referred to as protides, which target and inhibit the RNA-dependent RNA polymerase (NS5b) of HCV. The Company believes that, based on in vitro data, INX-189 is one of the most potent HCV nucleotide polymerase inhibitor currently in clinical development, and that results from preclinical studies and its Phase 1 trials of INX-189 to-date support its potential as a once-daily oral antiviral therapy amenable to fixed-dose combination with other antivirals for the treatment of patients with chronic hepatitis C infections.
About Shingles and FV-100
The Company is developing FV-100 to treat herpes zoster, also commonly referred to as shingles, which is an infection caused by the reactivation of varicella zoster virus (“VZV”), the same virus that causes chicken pox. Published in vitro studies have demonstrated that FV-100, an orally available bicyclic nucleoside analogue, is significantly more potent against VZV and can inhibit its replication substantially faster than any other antiviral agent currently approved for the treatment of shingles. Inhibitex believes these characteristics, a favorable pharmacokinetic profile, and the results of a recently-completed Phase 2 trial support the potential of FV-100 as a once-daily oral therapy to reduce the incidence, severity and duration of shingles-associated pain and PHN.
About Inhibitex
Inhibitex, Inc. is a biopharmaceutical company focused on developing products to treat and prevent serious infectious diseases. In addition to its two clinical-stage programs, INX-189 and FV-100, the Company’s pipeline includes other HCV nucleotide inhibitors in preclinical development. It has also licensed its proprietary MSCRAMM® protein platform to Pfizer for its use in the development of a staphylococcal vaccine, which is currently being evaluated in Phase 1 clinical trials.
For additional information about the Company, please visit http://www.inhibitex.com/
Safe Harbor Statement
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than historical facts included in this press release, including statements regarding: the anticipated time it will take the Company to conclude its assessment of the FV-100 Phase 2 data and the compound’s potential clinical, regulatory and commercial pathways; the potential for FV-100 to be dosed once daily and reduce the incidence, severity and duration of shingles-associated pain and PHN; the Company plans to enroll additional cohorts in the ongoing Phase 1b trial of INX-189; the time frame in which a Phase 2 clinical program of INX-189 can be initiated; the Company’s belief that INX-189 is one of the most potent HCV nucleotide polymerase inhibitor currently in clinical development; the results of preclinical studies and the Phase 1 trials of INX-189 to-date supporting its potential as a once-daily oral antiviral amenable to fixed dose combination with other antivirals; and the anticipated time when the ongoing Phase 1b trial of INX-189 will be completed, are forward looking statements. These intentions, expectations, or results may not be achieved in the future and various important factors could cause actual results or events to differ materially from the forward-looking statements that the Company makes, including the risk of: the Company, the FDA, a data safety monitoring board, or an institutional review board (IRB) delaying, suspending or terminating the clinical development of FV-100 or INX-189 at any time for a lack of safety, tolerability, antiviral activity, commercial viability, or any other reason; FV-100 not demonstrating sufficient activity or potential in reducing the incidence and severity of shingles-related pain and PHN, to be clinically relevant or commercially viable; the Company or its clinical investigators not being able to enroll additional HCV patients in the Phase 1b trial on a timely basis; obtaining, maintaining and protecting the intellectual property incorporated into and supporting the commercial viability of the Company’s product candidates; and other cautionary statements contained elsewhere herein and in its Annual Report on Form 10-K for the year ended December 31, 2009, as filed with the Securities and Exchange Commission, or SEC, on March 26, 2010, and its Quarterly Reports on Form 10-Q for the quarter ended March 31, 2010, June 30, 2010, and September 30, 2010, as filed with the SEC on May 13, 2010, August 12, 2010, and November 15, 2010, respectively. Given these uncertainties, you should not place undue reliance on these forward-looking statements, which apply only as of the date of this press release.
There may be events in the future that the Company is unable to predict accurately, or over which it has no control. The Company's business, financial condition, results of operations and prospects may change. The Company may not update these forward-looking statements, even though its situation may change in the future, unless it has obligations under the Federal securities laws to update and disclose material developments related to previously disclosed information. The Company qualifies all of the information contained in this press release, and particularly its forward-looking statements, by these cautionary statements.
Inhibitex® and MSCRAMM® are registered trademarks of Inhibitex, Inc.
Source
HIV Raises Risk of Broken Bones
Published: March 11, 2011
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
People with HIV are at higher risk of bone fractures than the general population, researchers reported.
And the increased risk appears to be driven mainly by fragility fractures at the wrist, vertebra, and femoral neck, according to Benjamin Young, MD, PhD, of the Rocky Mountain Center for AIDS Research, Education, and Services in Denver, and colleagues.
Factors such as older age, substance abuse, hepatitis C co-infection, and diabetes were associated with fracture risk, Young and colleagues reported online in Clinical Infectious Diseases.
One new finding, Young said in a statement, is that the state of the patient's immune system at its worst point -- that is, its lowest CD4 count -- is associated with an increased risk of fracture.
The findings may help improve clinical management of bone health in HIV-positive people, Young added, noting that the optimal care "is not well defined and remains controversial."
Low bone mineral density has been observed among HIV patients for many years, but there is limited data on the incidence of fractures, Young and colleagues noted.
An analysis of nearly 120,000 veterans, reported in 2010, suggested HIV was a risk factor for fragility fracture. And other studies have suggested the prevalence of fractures among those with HIV was increased, compared with other groups.
To look at fracture incidence, Young and colleagues turned to the long-running HIV Outpatient Study, an open, prospective observational cohort of HIV-positive people followed at 10 specialty clinics in eight U.S. cities.
The study has data on incident fractures from 2000 through 2008; Young and colleagues included all 5,826 participants who had at least two clinical visits during that time.
For comparison, they used data from the National Hospital Ambulatory Medical Care Survey of outpatient departments, which had fracture information through 2006.
The researchers found that the fracture rate rose over the first three years of the study -- from 57.7 per 10,000 population in 2000 to 84.8 in 2002. The change was significant at P=0.01, but the incidence rates stabilized in subsequent years.
On the other hand, rates of fracture in the outpatient survey did not change significantly from 2000 through 2006, the researchers reported.
But rates in the HIV cohort were always higher than those in the outpatient survey, they found:
• From 2000 through 2006, the incidence rates per 10,000 population in the HIV-positive cohort ranged from 57.5 to 83.2, with all but two (in 2000 and 2001) above 80.
• Over the same period, rates per 10,000 population in the outpatient survey ranged from 25.8 to 40.3.
• The differences were statistically significant in most years overall and for men, but not for women, who formed 21% of the HIV-positive cohort.
A multivariate analysis found that factors associated with fracture risk were age older than 47, nadir CD4-positive T-cell count below 200 cells per cubic millimeter, hepatitis C infection, diabetes, and substance abuse.
Men ages 25 through 54 in the HIV-positive cohort had significantly more fractures at the wrist and vertebra (at P<0.01 for each comparison) than did men of the same age in the outpatient survey.
Similarly, HIV-positive women ages 25 through 54 had more fractures at the vertebra and femoral neck sites, significant at P<0.01 and P=0.04, respectively.
But both men and women in the HIV-positive cohort had relatively fewer fractures at nonfragility sites, compared with those in the outpatient survey, Young and colleagues found.
Risk of a fragility fracture was associated in a multivariate analysis with:
• Increasing age, HR 1.43 per 10 years, 95% CI 1.03 to 1.98
• Hepatitis C, HR 1.99, 95% CI 1.01 to 3.90
• Body mass index less than 18.5, HR 3.72, compared with all other categories, 95% CI 1.14 to 12.09
The researchers cautioned that fracture incidence in the HIV-positive cohort was based on charts, and events were not confirmed by radiological findings or central adjudication.
They also noted that they did not have data for bone mineral density among those patients or use patterns for tobacco, alcohol, or other abused substances and so were unable to assess contribution of these to fracture rates.
The study was supported by the CDC.
Young reported financial links with Cerner, Gilead Sciences, Merck, GlaxoSmithKline, and Viiv Healthcare.
Primary source: Clinical Infectious Diseases
Source reference:
Young B, et al "Increased rates of bone fracture among HIV-infected persons in the HIV Outpatient Study (HOPS) compared with the U.S. general population, 2000-2006" Clin Infect Dis 2010; 52(8): 1061-1068.
Source
Hepatic Encephalopathy
From: The American Liver Foundation
Explore this section to learn more about Hepatic Encephalopathy, including a description of the disease and how it's diagnosed.
Why is the liver important?
The liver is the second largest organ in your body and is located under your rib cage on the right side. It weighs about three pounds and is shaped like a football that is flat on one side.
The liver performs many jobs in your body. It processes what you eat and drink into energy and nutrients your body can use. The liver also removes harmful substances from your blood.
What is hepatic encephalopathy?
Hepatic encephalopathy (HE) is a brain disorder that is caused by liver damage. HE can be an acute (short-term) or chronic (long-term) condition and can be mild, moderate, or severe.
What causes an episode of hepatic encephalopathy?
HE occurs when the liver is damaged and cannot remove toxic chemicals, such as ammonia, from the blood. These chemicals then enter the brain and cause it to not function well.
The following factors may trigger HE:
HE can cause mental and physical symptoms. They can vary person to person, and may progress slowly or occur suddenly.
Symptoms may include:
Complications of HE may include:
HE can be a medical emergency and hospitalization is usually required. It is important to see a doctor as soon as symptoms begin. At the hospital, doctors determine and treat what may have caused hepatic encephalopathy. Treatments aim to manage the disease and keep people out of the hospital.
Depending on the cause, treatments may include:
The best way to reduce the risk of HE is to prevent, treat, or manage liver disease. Talk to your doctor about risk factors and steps that can be taken to prevent chronic HE.
Facts-At-A-Glance
Explore this section to learn more about Hepatic Encephalopathy, including a description of the disease and how it's diagnosed.
Why is the liver important?
The liver is the second largest organ in your body and is located under your rib cage on the right side. It weighs about three pounds and is shaped like a football that is flat on one side.
The liver performs many jobs in your body. It processes what you eat and drink into energy and nutrients your body can use. The liver also removes harmful substances from your blood.
What is hepatic encephalopathy?
Hepatic encephalopathy (HE) is a brain disorder that is caused by liver damage. HE can be an acute (short-term) or chronic (long-term) condition and can be mild, moderate, or severe.
What causes an episode of hepatic encephalopathy?
HE occurs when the liver is damaged and cannot remove toxic chemicals, such as ammonia, from the blood. These chemicals then enter the brain and cause it to not function well.
The following factors may trigger HE:
- Dehydration (loss of water from the body)
- Low oxygen levels in the body
- Eating too much protein
- Constipation
- Medications that affect the nervous system, such as tranquilizers or sleep medications
- Infections
- Intestine, stomach, or esophagus bleeding
- Kidney problems
- Surgery
HE can cause mental and physical symptoms. They can vary person to person, and may progress slowly or occur suddenly.
Symptoms may include:
- Mild confusion
- Forgetfulness
- Personality or mood changes
- Poor concentration
- Poor judgment
- Stale or sweet odored breath
- Change in sleep patterns
- Worsening of handwriting or small hand movements
- Unusual movements or shaking of hands or arms (also known as “flapping”)
- Extreme anxiety
- Seizures
- Severe confusion
- Sleepiness or fatigue
- Severe personality changes
- Jumbled and slurred speech
- Slow movement
Complications of HE may include:
- Brain swelling
- Permanent nervous system damage
- Increased risk of heart failure, kidney failure, respiratory failure and sepsis (blood poisoning)
- Coma
HE can be a medical emergency and hospitalization is usually required. It is important to see a doctor as soon as symptoms begin. At the hospital, doctors determine and treat what may have caused hepatic encephalopathy. Treatments aim to manage the disease and keep people out of the hospital.
Depending on the cause, treatments may include:
- Stopping intestine, stomach, and esophagus bleeding
- Healing infections
- Addressing kidney failure
- Providing life support if the person is in a coma
- Diet changes such as avoiding too much or too little protein
- Rifaximin (Xifaxan) to reduce bacteria in the intestines that make toxins the liver cannot process
- Lactulose (type of sugar) to prevent the liver from absorbing toxins from the intestine
- Prevention and treatment of constipation
- Medicine to remove blood from the intestines or procedures to control active bleeding
- Medicine to treat infections
The best way to reduce the risk of HE is to prevent, treat, or manage liver disease. Talk to your doctor about risk factors and steps that can be taken to prevent chronic HE.
Facts-At-A-Glance
- Hepatic encephalopathy (HE) is a brain disorder caused by liver damage
- HE can be an acute (short-term) or chronic (long-term) condition and can be mild, moderate, or severe
- HE occurs when the liver cannot remove toxic chemicals in the blood and these chemicals enter the brain
- Symptoms of HE may progress slowly, or may occur suddenly
- Common symptoms of HE include confusion, forgetfulness, personality or mood changes, poor concentration and judgment, stale or sweet odored breath, change in sleep patterns, and worsening of handwriting or small hand movements
- People with HE can enter a coma or have brain damage
- HE can be a medical emergency and hospitalization is usually required
- Treatments aim to manage the disease and keep people out of the hospital
- The best way to reduce the risk of HE is to prevent, treat, or manage liver disease
Know Your ALT
The Serum Alt: Frequently Asked Questions
What is it?
The ALT is a protein manufactured in the liver which participates in metabolism. The term ALT refers to alanine-amino transferase. This protein is an enzyme which participates in modifying amino acids, the building blocks of proteins. The ALT is made predominately in the liver and therefore alterations in the serum ALT can be directly related to disturbances of liver structure and function.
Is the serum ALT hard to measure?
It is straightforward to have ones blood sample tested for a serum ALT, it only requires obtaining a blood sample. The serum ALT is easily measured in laboratories throughout the world. The methodology may vary from laboratory to laboratory, making direct comparisons of the absolute serum ALT value difficult, but all laboratories have a normal range for men and women.
What does an elevated serum ALT reflect?
The ALT is manufactured within liver cells. Elevations in the serum ALT reflect alterations in the structure and function of the liver. Damaged liver cells release ALT into the blood stream where it can then be measured. The serum ALT, therefore, reflects damage to liver cells, liver injury, and underlying liver disease.
Why should I know my serum ALT?
We should all be aware of our health. Unfortunately, unlike diseases affecting other organs, injury to the liver can be silent. Patients may not have any symptoms and the ALT can be elevated for years before one is aware of an underlying liver disease. When one develops symptoms from liver disease, it usually reflects advanced damage to the liver. Once significant damage to the liver has occurred, therapies other than liver transplantation, may not be very beneficial. Therefore, making the diagnosis of a liver disease early in its course can be very beneficial in regards to receiving specific therapies and modifying lifestyle.
My doctor also measures other blood tests. What are they and is the serum ALT the best test?
The liver is a complex organ with a variety of essential functions for the body. It participates in metabolism, produces bile, and generates proteins secreted into the blood, so your doctor may measure compounds associated with all of these liver functions. All of those tests are frequently measured in a battery of tests referred to as a “liver panel.” Depending upon the type and nature of the underlying liver injury and therefore the liver disease, changes in the magnitude of the various components of this panel provide meaningful information to your physician. However, if one simply wants to know whether one has liver wellness or may have an underlying liver disease, the ALT is likely the most sensitive test for the vast majority of liver illness.
Is there a direct correlation between the magnitude of the serum ALT elevation and the severity of the underlying liver disease?
Although there can be a relationship between the magnitude of elevation in the serum ALT and the severity of the abnormalities in liver structure and function, this relationship is not absolute. Patients with advanced scarring of the liver may have significant liver dysfunction despite only mild elevations of the serum ALT. Therefore, any elevation of the serum ALT should be taken seriously and one should seek appropriate medical care to determine the cause.
What are some common causes of an elevated serum ALT?
Perhaps the most common cause in the North American population is fat accumulation within liver cells. Fat can accumulate anywhere in the body, but its accumulation in the liver cells is toxic to the liver. In particular, patients who are above their ideal body weight, have diabetes, or elevations in their blood lipids, may be at risk for having fat within the liver. The serum ALT is a common approach to determine whether one may have fat in the liver and if it is injurious to this organ. Other common causes of an elevated serum ALT include excessive consumption of alcohol, infection by chronic hepatitis viruses such as hepatitis B and C, toxicity from pharmaceutical medications, a genetic liver disease associated with an excess accumulation of iron in the liver, and autoimmune liver diseases. The latter are a variety of liver diseases in which the body’s immune system inflicts damage on ones own organ.
I have an elevated ALT. What should I do?
If you have an elevated ALT, you should seek medical attention. The vast majority of primary care physicians and specialists in gastroenterology and hepatology, can perform the necessary testing to determine the cause of an elevated serum ALT.
How often should I have my serum ALT measured?
Like the serum cholesterol and blood glucose tests for elevated cholesterol and diabetes, respectively; one should have the serum ALT measured repeatedly and regularly over time. A conservative approach would be to have ones serum ALT measured on an annual basis during the annual physical examination.
Source
What is it?
The ALT is a protein manufactured in the liver which participates in metabolism. The term ALT refers to alanine-amino transferase. This protein is an enzyme which participates in modifying amino acids, the building blocks of proteins. The ALT is made predominately in the liver and therefore alterations in the serum ALT can be directly related to disturbances of liver structure and function.
Is the serum ALT hard to measure?
It is straightforward to have ones blood sample tested for a serum ALT, it only requires obtaining a blood sample. The serum ALT is easily measured in laboratories throughout the world. The methodology may vary from laboratory to laboratory, making direct comparisons of the absolute serum ALT value difficult, but all laboratories have a normal range for men and women.
What does an elevated serum ALT reflect?
The ALT is manufactured within liver cells. Elevations in the serum ALT reflect alterations in the structure and function of the liver. Damaged liver cells release ALT into the blood stream where it can then be measured. The serum ALT, therefore, reflects damage to liver cells, liver injury, and underlying liver disease.
Why should I know my serum ALT?
We should all be aware of our health. Unfortunately, unlike diseases affecting other organs, injury to the liver can be silent. Patients may not have any symptoms and the ALT can be elevated for years before one is aware of an underlying liver disease. When one develops symptoms from liver disease, it usually reflects advanced damage to the liver. Once significant damage to the liver has occurred, therapies other than liver transplantation, may not be very beneficial. Therefore, making the diagnosis of a liver disease early in its course can be very beneficial in regards to receiving specific therapies and modifying lifestyle.
My doctor also measures other blood tests. What are they and is the serum ALT the best test?
The liver is a complex organ with a variety of essential functions for the body. It participates in metabolism, produces bile, and generates proteins secreted into the blood, so your doctor may measure compounds associated with all of these liver functions. All of those tests are frequently measured in a battery of tests referred to as a “liver panel.” Depending upon the type and nature of the underlying liver injury and therefore the liver disease, changes in the magnitude of the various components of this panel provide meaningful information to your physician. However, if one simply wants to know whether one has liver wellness or may have an underlying liver disease, the ALT is likely the most sensitive test for the vast majority of liver illness.
Is there a direct correlation between the magnitude of the serum ALT elevation and the severity of the underlying liver disease?
Although there can be a relationship between the magnitude of elevation in the serum ALT and the severity of the abnormalities in liver structure and function, this relationship is not absolute. Patients with advanced scarring of the liver may have significant liver dysfunction despite only mild elevations of the serum ALT. Therefore, any elevation of the serum ALT should be taken seriously and one should seek appropriate medical care to determine the cause.
What are some common causes of an elevated serum ALT?
Perhaps the most common cause in the North American population is fat accumulation within liver cells. Fat can accumulate anywhere in the body, but its accumulation in the liver cells is toxic to the liver. In particular, patients who are above their ideal body weight, have diabetes, or elevations in their blood lipids, may be at risk for having fat within the liver. The serum ALT is a common approach to determine whether one may have fat in the liver and if it is injurious to this organ. Other common causes of an elevated serum ALT include excessive consumption of alcohol, infection by chronic hepatitis viruses such as hepatitis B and C, toxicity from pharmaceutical medications, a genetic liver disease associated with an excess accumulation of iron in the liver, and autoimmune liver diseases. The latter are a variety of liver diseases in which the body’s immune system inflicts damage on ones own organ.
I have an elevated ALT. What should I do?
If you have an elevated ALT, you should seek medical attention. The vast majority of primary care physicians and specialists in gastroenterology and hepatology, can perform the necessary testing to determine the cause of an elevated serum ALT.
How often should I have my serum ALT measured?
Like the serum cholesterol and blood glucose tests for elevated cholesterol and diabetes, respectively; one should have the serum ALT measured repeatedly and regularly over time. A conservative approach would be to have ones serum ALT measured on an annual basis during the annual physical examination.
Source
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