Telaprevir-Based Regimen as Good for Hep C Over 24 Weeks as 48 Weeks
August 10, 2010
A treatment regimen containing the experimental hepatitis C virus (HCV) antiviral telaprevir can cure HCV after 24 weeks of treatment—without requiring a full 48-week course of therapy—in people with HCV genotype 1 who have undetectable virus levels after 4 and 12 weeks of therapy. These early results from a clinical trial conducted by Vertex Pharmaceuticals were reported in a press release from the company.
Telaprevir is a member of a new class of HCV therapies called protease inhibitors. Studies suggest that telaprevir, when combined with the standard drugs pegylated interferon and ribavirin, can increase success rates by 50 percent or more. Treatment success, called a sustained virological response—or SVR—means achieving and maintaining undetectable HCV levels for six months after completing a course of HCV treatment.
Results from a Phase III clinical trial called ADVANCE suggest that telaprevir works well for patients with HCV genotype 1, which is the most common yet difficult-to-treat form of HCV in the United States. Whereas patients with HCV genotype 1 typically require 48 weeks of treatment, ADVANCE suggested that combining telaprevir with standard therapy for the first 12 weeks of treatment increased the percentage of people with undetectable genotype 1 HCV levels after 4 and 12 weeks, compared with standard therapy alone. In these patients, dubbed extended rapid virologic responders (eRVRs), all drugs could be stopped after just 24 weeks without jeopardizing the likelihood of an SVR.
As encouraging as these results were, researchers and advocates remained skeptical. In turn, Vertex’s researchers designed a second Phase III study, called ILLUMINATE. In that study, Kenneth Sherman, MD, PhD—from the University of Cincinnati College of Medicine and a principal investigator of the trial—and his colleagues enrolled 500 people who had HCV genotype 1, none of whom had been treated previously, and randomized them to either 24 or 48 weeks of HCV treatment.
All of the participants in ILLUMINATE took standard HCV treatment—pegylated interferon plus ribavirin—combined with telaprevir for 12 weeks. After 12 weeks, people stopped the telaprevir and continued on therapy for an additional 12 weeks (24 weeks of treatment in all).
Patients who achieved an eRVR—undetectable HCV levels after 4 and 12 weeks of therapy—were then randomized to either stop therapy altogether after 24 weeks or continue treatment for a total of 48 weeks. Patients who did not have a eRVR were automatically continued on standard therapy for 48 weeks.
The analysis described in the Vertex press release involved only those who achieved an eRVR and were randomized to either discontinue or remain on therapy after 24 weeks. Full results from the study, including those who did not achieved an eRVR, will be reported at a later date.
Overall, Sherman and his colleagues found that eRVRs who stayed on treatment for 48 weeks had no more chance of treatment success than those who completed only 24 weeks of treatment. In all, 92 percent of eRVRs who took 24 weeks of treatment were cured of HCV, compared with 88 percent who took treatment for 48 weeks.
The percentage of people who had undetectable HCV levels at the end of treatment but whose HCV later returned (relapsers) was 5.9 percent in eRVRs on 24 weeks of treatment compared with 1.9 percent of those on 48 weeks of treatment.
The overall number of people who achieved an HCV genotype 1 cure, regardless of their early virologic response, was also relatively high, at 72 percent.
“The viral cure rates seen in ILLUMINATE showed that there was no benefit to extending telaprevir-based therapy to 48 weeks for the majority of people,” Sherman said. “Patients who had a rapid response to telaprevir-based regimens at weeks four and 12 had a high likelihood of achieving a cure with 24 weeks of total treatment, which may provide important information to motivate people to continue therapy.”
Thus far, studies have taken place only in HCV monoinfected individuals—people infected only with HCV, not coinfected with HIV and HCV. Trials in HIV-coinfected people are planned and should get underway in the coming months. In the meantime, however, good results in monoinfected people offer real hope to people who are coinfected. Facing the prospect of 48 weeks of current HCV treatment—which has significant side effects and only works 25 percent of the time—many coinfected people feel conflicted about starting therapy. A new treatment, however, that offers the chance of better results in half the time would represent a significant advance.
Search: Vertex, telaprevir, hepatitis C virus, Hep C, HCV, sustained virological response, ADVANCE, ILLUMINATE
Source
Vertex: telaprevir could shorten hep C treatment
(AP) – 1 hour ago
CAMBRIDGE, Mass. — Vertex Pharmaceuticals Inc. said Tuesday that a study showed some patients who take its hepatitis C drug candidate telaprevir may be able to complete their treatment sooner.
Vertex said patients who responded quickly to treatment with telaprevir had better results after 24 weeks of therapy than after 48 weeks. The company said that shows a 24-week regimen including telaprevir can be an effective treatment for the disease.
Vertex highlighted results for patients who responded well to telaprevir, as they had undetectable levels of the hepatitis C virus after 4 weeks and 12 weeks of treatment. Treatment in the study included 12 weeks of telaprevir in combination with two older drugs, pegylated interferon and ribavirin. That was followed by additional treatment with pegylated interferon and ribavirin alone.
The patients who had undetectable virus levels after 4 weeks and 12 weeks were treated with pegylated interferon and ribavirin for either 12 more weeks or 36 more weeks. Of the patients who were treated for an additional 12 weeks — making 24 weeks of therapy in total — Vertex said 92 percent had undetectable levels of the hepatitis C virus. It said 88 percent of the patients who received 48 weeks of treatment had undetectable virus levels.
Patients' virus levels were measured 24 weeks after the end of their treatment.
The clinical trial was called ILLUMINATE. Patients who did not have a quick response to telaprevir were given pegylated interferon and ribavirin alone for 48 weeks.
The company plans to file for Food and Drug Administration approval of telaprevir in the fourth quarter. The drug is seen as a potential billion-seller for Vertex.
The most common side effects of telaprevir treatment were fatigue, itching, nausea, anemia, rash, and headache. Vertex said most of those side effects were mild or moderate.
In morning trading, Vertex shares fell 75 cents, or 2 percent, to $36.25.
(This version CORRECTS details on the design of the trial.)
Copyright © 2010 The Associated Press. All rights reserved.
Source
AUGUST 10, 2010, 10:34 A.M. ET.
Vertex Reports Success In Second Major Hepatitis Drug Study
By Thomas Gryta Of DOW JONES NEWSWIRES NEW YORK (Dow Jones)--Vertex Pharmaceuticals Inc. (VRTX) reported the success of the second of three key late-stage studies of hepatitis-C treatment, telaprevir, essentially curing 72% of patients using the drug.
The study, a supplement to the larger studies intended to support teleprevir's approval, showed there was no benefit to extending treatment to 48 weeks from 24 weeks in the majority of patients. The results are notable because they improve the sustained viral response, or SVR, which is essentially a cure for the liver disease, and shorten the length of therapy for most patients.
Vertex shares recently slid 2.3% to $36.14 on a down day for the market so far. The study's success was largely expected as investors watch for the data of all three studies, the last of which is coming in September, to gauge telaprevir's place in a competitive hepatitis C market. Vertex's shares, up 11% since late July, rose 2.3% in the wake of news of the first study's success in May.
Hepatitis C is a blood-transmitted virus that causes liver inflammation and can lead to cirrhosis, cancer and liver failure.
The current standard therapy, a combination of pegylated-interferon injections and ribavirin pills over 48 weeks, achieves an SVR in up to about 50% of patients, according to the Centers for Disease Control.
The latest study, called Illuminate, included 540 people infected with the genotype 1 strain of the virus, its most common form in the U.S. and Europe.
The trial is considered supplemental, as it is a single-armed study with no patient group taking a placebo, as they do in the other late-stage studies.
In the Illuminate trial, all patients received telaprevir for 12 weeks with standard therapy, with interferon and ribavirin continuing for another 12 weeks.
The results showed a cure for 72% of all patients in the trial. For the 65% of patients showing an early response to the drug, those on a 24-week regimen showed a 92% SVR rate and a 48-week group achieved SVR in 88% of patients. The relapse rate in the short regimen was 5.7%, compared with 1.9% in the longer group.
Vertex plans to complete its marketing application to the Food and Drug Administration before the end of the year. The company plans to market the drug itself in North America, while Johnson & Johnson (JNJ) will help sell telaprevir overseas, with Mitsubishi Tanabe Pharma Corp. (4508.TO) holding rights in Japan and some other Asian countries.
Vertex said the side-effect profile in telaprevir's latest trial was consistent with that of earlier studies, including fatigue, itching, nausea, and anemia. Side effects led to discontinuation of therapy during the first 12 weeks in 6.9% of patients.
Last week, Merck & Co. (MRK) reported positive results from two large studies of its own Hepatitis therapy, boceprevir, which it plans to submit for regulatory approval in the U.S. and Europe this year.
At the time, analysts perceived the telaprevir data as more impressive.
Both the Merck and Vertex drugs are known as protease inhibitors, which are designed to block an enzyme that helps hepatitis C virus replicate. Standard treatment is a combination of the drug pegylated interferon and ribavirin. The hope is that protease inhibitors can improve cure rates versus standard treatment, and potentially shorten the duration of treatment.
Many other companies are developing hepatitis C treatments, including Bristol-Myers Squibb Co. (BMY), Gilead Sciences Inc. (GILD) and Roche Holding AG (RHHBY, ROG.VX).
-By Thomas Gryta, Dow Jones Newswires; 212-416-2169; thomas.gryta@dowjones.com
Source
Vertex hep C drug works in 24 weeks for many -study
By Bill Berkrot
NEW YORK
Tue Aug 10, 2010 7:07pm IST
NEW YORK (Reuters) - A study of Vertex Pharmaceuticals Inc's high profile experimental hepatitis C drug showed that the overwhelming majority of previously untreated patients who respond early to telaprevir can be cured in half the time of current therapy.
Of the so-called rapid viral responders, 92 percent of patients who received a total of 24 weeks of therapy with telaprevir plus the standard treatment of pegylated interferon and ribavirin achieved sustained virologic response, or SVR, which is considered tantamount to a cure.
The overall cure rate for all telaprevir patients was 72 percent, a touch below the 75 percent seen in an earlier Phase III trial. But most patients in whom the virus is cleared early may be able to complete treatment in half the time of current tough to tolerate therapy, the data showed.
New data on the drug, which some analysts believe could eventually capture annual sales of more than $4 billion if it is approved, lifted shares of Vertex 3.7 percent to $38.40 in premarket trading on Nasdaq.
The lofty hopes for telaprevir are based on its ability to cure a far higher percentage of patients than standard drugs and its potential to cut treatment duration.
In the earlier Phase III trial of previously untreated patients interferon and ribavirin without telaprevir cured only 44 percent of patients. Those drugs must be taken for 48 weeks and often cause debilitating flu-like symptoms, leading many patients to discontinue their use.
The latest late-stage trial separated out patients in whom the virus was undetectable at both week 4 and 12 of treatment with the three-drug combination to see if there was any advantage to extending therapy with standard drugs beyond 24 weeks to the full 48 weeks in those patients.
Sixty-five percent of the 540 trial participants fell into the rapid responder category. In all cases telaprevir was part of the regimen for the first 12 weeks.
Among those rapid responders, there was an 88 percent cure rate with the full 48 weeks -- slightly less than with 24 weeks. But there was a lower relapse rate with the 48-week group -- 1.9 percent versus 5.7 percent with the 24-week regimen, or 3 patients versus 9.
"Patients who had a rapid response to telaprevir-based regimens at weeks 4 and 12 had a high likelihood of achieving a cure with 24 weeks of total treatment, which may provide important information to motivate people to continue therapy," Dr Kenneth Sherman, principal investigator of the trial, said in a statement.
The company next month is expected to release data from one more Phase III study, this time in much tougher-to-treat patients who failed to be helped by prior therapy with standard drugs.
The three late-stage trials will form the basis for Vertex's application seeking approval of the drug that it plans to file with the U.S. Food and Drug Administration by the end of the year.
Telaprevir, from a new class of hepatitis C treatments, is expected to compete with a similar drug being developed by Merck & Co called boceprevir. But analysts have been virtually unanimous in their belief that telaprevir is the better of the two drugs.
Boceprevir led to an overall cure rate of 66 percent in a study recently released by Merck.
The safety and tolerability of telaprevir in the latest Vertex trial was similar to what was seen in the earlier late-stage study, the company said.
Adverse events, including rash and anemia, led to a discontinuation rate of nearly 7 percent of patients.
(Reporting by Bill Berkrot; Editing by Gary Hill, Dave Zimmerman)
Source
August 10, 2010
RNA Interference inhibits Hepatitis B Virus of different genotypes in Vitro and in Vivo
Published on: 2010-08-10
Hepatitis B virus (HBV) infection increases the risk of liver disease and hepatocellular carcinoma. Small interfering RNA (siRNA) offers a new tool with potential therapeutic applications for HBV.
Given the high heterogeneity of HBV strains and the sensitivity of siRNA to the changes of sequences, finding potent siRNA inhibitors against the conservative site on HBV genome is essential to ensure the therapeutic application.
Results: Forty short hairpin RNA (shRNA) expression plasmids were constructed targeting conserved regions among 9 HBV genotypes. HBV 1.3-fold genome plasmids with various genotypes were co-transfected with shRNA plasmids to Huh7 cells or to mice.
The levels of various viral proteins were examined to assess anti-HBV efficacy of siRNA. Four shRNA plasmids (B245, B376, B1581 and B1789 ) were found to be able to potently inhibit HBV surface antigen (HBsAg), e antigen (HBeAg) and core antigen (HBcAg) expression of HBV genotypes A, B, C, D and I (a newly identified genotype ) both in Huh7 cells and in mice.
No unusual cytotoxicity or off-target effects were noted.
Conclusions: Such siRNA suggest an alternate way of inhibiting various HBV genotypes in vitro and in vivo, promising an advance in treatment of HBV.
Author: Ya-Li ZhangTong ChengYi-Jun CaiQuan YuanChe LiuTao ZhangDe-Zhen XiaRui-Ying LiLian-Wei YangYing-Bin WangAnthony YeoJames ShihJun ZhangNing-Shao Xia
Credits/Source: BMC Microbiology 2010, 10:214
Source
Hepatitis B virus (HBV) infection increases the risk of liver disease and hepatocellular carcinoma. Small interfering RNA (siRNA) offers a new tool with potential therapeutic applications for HBV.
Given the high heterogeneity of HBV strains and the sensitivity of siRNA to the changes of sequences, finding potent siRNA inhibitors against the conservative site on HBV genome is essential to ensure the therapeutic application.
Results: Forty short hairpin RNA (shRNA) expression plasmids were constructed targeting conserved regions among 9 HBV genotypes. HBV 1.3-fold genome plasmids with various genotypes were co-transfected with shRNA plasmids to Huh7 cells or to mice.
The levels of various viral proteins were examined to assess anti-HBV efficacy of siRNA. Four shRNA plasmids (B245, B376, B1581 and B1789 ) were found to be able to potently inhibit HBV surface antigen (HBsAg), e antigen (HBeAg) and core antigen (HBcAg) expression of HBV genotypes A, B, C, D and I (a newly identified genotype ) both in Huh7 cells and in mice.
No unusual cytotoxicity or off-target effects were noted.
Conclusions: Such siRNA suggest an alternate way of inhibiting various HBV genotypes in vitro and in vivo, promising an advance in treatment of HBV.
Author: Ya-Li ZhangTong ChengYi-Jun CaiQuan YuanChe LiuTao ZhangDe-Zhen XiaRui-Ying LiLian-Wei YangYing-Bin WangAnthony YeoJames ShihJun ZhangNing-Shao Xia
Credits/Source: BMC Microbiology 2010, 10:214
Source
News From Journal Of Clinical Investigation Online: Aug. 9, 2010
Article Date: 10 Aug 2010 - 4:00 PDT
ONCOLOGY: Identifying liver cancer stem cells
A subpopulation of cells in a tumor that are known as cancer stem cells (CSCs) are thought to be involved in tumor resistance to chemo/radiation therapy as well as tumor relapse and progression. However, whether CSCs exist in many cancers and what their identity is has been hard to determine. A team of researchers, led by Masaki Mori, at Osaka University, Japan, has now determined that CD13 is a marker for CSCs in human liver cancer cell lines and clinical samples. Furthermore, combining a CD13 inhibitor with the chemotherapeutic agent 5-FU drastically reduced tumor volume compared with either agent alone in mouse xenograft models, leading the authors to suggest that targeting the CD13+ CSCs might provide a way to treat patients with liver cancer.
Title:
CD13 is a therapeutic target in human liver cancer stem cells
DRUG DEVELOPMENT: Improving RNAi efficacy, toxicity, and persistence
In several clinical trials, RNAi-based therapies have been shown to be effective and well tolerated. However, animal studies suggest that there is a need for caution, as RNAi can trigger cell death leading to organ failure and lethality. It is believed that these adverse effects are a result of saturation of endogenous cellular RNAi factors such as Xpo-5. A team of researchers, led by Mark Kay, at Stanford University, California, has now generated substantive data in mice to support the idea that RNAi-based therapies overload the endogenous RNAi pathway to cause liver damage, and developed ways to overcome this problem.
In the study, members of the human Ago family of proteins were found to be involved in saturation of endogenous cellular RNAi, with Ago-2 particularly prone to saturation and acting as a rate-limiting determinant of both in vitro and in vivo RNAi efficacy, toxicity, and persistence. The authors then developed two ways to enhance RNAi efficacy and persistence while decreasing toxicity, approaches that they hope will improve human RNAi-based therapies. First, in adult mice, vector-based Ago-2/Xpo-5 coexpression enhanced RNAi silencing in the liver, reduced liver damage, and extended RNAi stability. Second, minimizing shRNA expression reduced liver damage while still permitting long-term gene silencing.
Title:
Argonaute proteins are key determinants of RNAi efficacy, toxicity, and persistence in the adult mouse liver
ONCOLOGY: Subdividing cancers in mice identifies distinct human tumor subtypes
Some cancers can be divided into subtypes depending on the signaling pathways that drive tumor development. This can help determine which therapy is most appropriate, for example breast cancers lacking expression of the proteins to which hormones bind do not respond to hormone-based therapies. A team of researchers, led by Rama Khokha, at Ontario Cancer Institute, Toronto, has now generated a new mouse model of osteosarcoma (the most common type of bone tumor) and found that deletions of the Prkar1a gene characterize a molecularly distinct subtype of mouse osteosarcoma featuring overexpression of the protein RANKL. Human tumors could also be divided based on high and low expression of PRKAR1A, with low levels of expression being associated with a greater likelihood of responding to chemotherapy. The authors therefore conclude that information gleaned in mice can help divide human tumors into clinically relevant subtypes.
Title:
Prkar1a is an osteosarcoma tumor suppressor that defines a molecular subclass in mice
CARDIOVASCULAR DISEASE: Heart protection via myeloid MR
Drugs that target the protein MR are used to treat diseases of the blood vessels and heart (i.e., cardiovascular diseases). Although some of their benefit is a result of blocking binding of the steroid hormone aldosterone to MR, data indicate that some of their effects are aldosterone independent. A team of researchers, led by Richard Mortensen, at the University of Michigan Medical School, Ann Arbor, and Sheng Zhong Duan, at Shanghai Institutes for Biological Sciences, China, has now shown that mice lacking MR on immune cells known as myeloid cells are protected against heart and blood vessel damage in the same way that mice treated with drugs targeting MR are. Further analysis indicated that MR on myeloid cells is necessary for efficient classical activation of myeloid immune cells known as macrophages by proinflammatory cytokines. These data provide new insight into the mechanisms underlying the beneficial effects of drugs that target MR.
Title:
Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice
Source:
Karen Honey
Journal of Clinical Investigation
Source
ONCOLOGY: Identifying liver cancer stem cells
A subpopulation of cells in a tumor that are known as cancer stem cells (CSCs) are thought to be involved in tumor resistance to chemo/radiation therapy as well as tumor relapse and progression. However, whether CSCs exist in many cancers and what their identity is has been hard to determine. A team of researchers, led by Masaki Mori, at Osaka University, Japan, has now determined that CD13 is a marker for CSCs in human liver cancer cell lines and clinical samples. Furthermore, combining a CD13 inhibitor with the chemotherapeutic agent 5-FU drastically reduced tumor volume compared with either agent alone in mouse xenograft models, leading the authors to suggest that targeting the CD13+ CSCs might provide a way to treat patients with liver cancer.
Title:
CD13 is a therapeutic target in human liver cancer stem cells
DRUG DEVELOPMENT: Improving RNAi efficacy, toxicity, and persistence
In several clinical trials, RNAi-based therapies have been shown to be effective and well tolerated. However, animal studies suggest that there is a need for caution, as RNAi can trigger cell death leading to organ failure and lethality. It is believed that these adverse effects are a result of saturation of endogenous cellular RNAi factors such as Xpo-5. A team of researchers, led by Mark Kay, at Stanford University, California, has now generated substantive data in mice to support the idea that RNAi-based therapies overload the endogenous RNAi pathway to cause liver damage, and developed ways to overcome this problem.
In the study, members of the human Ago family of proteins were found to be involved in saturation of endogenous cellular RNAi, with Ago-2 particularly prone to saturation and acting as a rate-limiting determinant of both in vitro and in vivo RNAi efficacy, toxicity, and persistence. The authors then developed two ways to enhance RNAi efficacy and persistence while decreasing toxicity, approaches that they hope will improve human RNAi-based therapies. First, in adult mice, vector-based Ago-2/Xpo-5 coexpression enhanced RNAi silencing in the liver, reduced liver damage, and extended RNAi stability. Second, minimizing shRNA expression reduced liver damage while still permitting long-term gene silencing.
Title:
Argonaute proteins are key determinants of RNAi efficacy, toxicity, and persistence in the adult mouse liver
ONCOLOGY: Subdividing cancers in mice identifies distinct human tumor subtypes
Some cancers can be divided into subtypes depending on the signaling pathways that drive tumor development. This can help determine which therapy is most appropriate, for example breast cancers lacking expression of the proteins to which hormones bind do not respond to hormone-based therapies. A team of researchers, led by Rama Khokha, at Ontario Cancer Institute, Toronto, has now generated a new mouse model of osteosarcoma (the most common type of bone tumor) and found that deletions of the Prkar1a gene characterize a molecularly distinct subtype of mouse osteosarcoma featuring overexpression of the protein RANKL. Human tumors could also be divided based on high and low expression of PRKAR1A, with low levels of expression being associated with a greater likelihood of responding to chemotherapy. The authors therefore conclude that information gleaned in mice can help divide human tumors into clinically relevant subtypes.
Title:
Prkar1a is an osteosarcoma tumor suppressor that defines a molecular subclass in mice
CARDIOVASCULAR DISEASE: Heart protection via myeloid MR
Drugs that target the protein MR are used to treat diseases of the blood vessels and heart (i.e., cardiovascular diseases). Although some of their benefit is a result of blocking binding of the steroid hormone aldosterone to MR, data indicate that some of their effects are aldosterone independent. A team of researchers, led by Richard Mortensen, at the University of Michigan Medical School, Ann Arbor, and Sheng Zhong Duan, at Shanghai Institutes for Biological Sciences, China, has now shown that mice lacking MR on immune cells known as myeloid cells are protected against heart and blood vessel damage in the same way that mice treated with drugs targeting MR are. Further analysis indicated that MR on myeloid cells is necessary for efficient classical activation of myeloid immune cells known as macrophages by proinflammatory cytokines. These data provide new insight into the mechanisms underlying the beneficial effects of drugs that target MR.
Title:
Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice
Source:
Karen Honey
Journal of Clinical Investigation
Source
How should we assess quality of cirrhosis care?
Posted on August 5, 2010 by Kristine Novak, PhD, Science Editor
Insurance companies and government agencies attempt to assess healthcare quality to develop quality-based reimbursement models. It is a challenge to define and measure quality of care, however, especially for complex, chronic diseases such as cirrhosis. Two studies in the August issue of Clinical Gastroenterology and Hepatology (CGH) identify tools for determining quality of care for patients with cirrhosis.
Fasiha Kanwal et al. identified quality indicators for treatment of patients with cirrhosis. A panel of 11 experts established a list of 41 quality indicators for 6 areas of care—ascites, variceal bleeding, hepatic encephalopathy, hepatocellular cancer, liver transplantation, and general cirrhosis care. In a related CGH podcast co-author Bruce Bacon describes the final 8 most important quality indicators selected by the panel. The authors conclude that this list begins to fill the void of quality assessment in cirrhosis; physicians might also use this list to identify processes in cirrhosis care that can be modified to improve patient outcomes. However, before this list is used in assessment processes, we must determine how adherence to this list of quality indicators actually affects outcomes. A better system to measure and track quality indicators also needs to be developed.
Hepatitis C-specific quality indicators have been implemented as part of the Medicare’s Physician Quality Reporting Initiative, a voluntary program that connects reimbursement incentive to compliance with performance using quality indicators. Kanwal et al. believe that with the increasing burden of cirrhosis, Medicare might extend the quality reporting initiatives to include the cirrhosis metrics, and that insurers will follow. The authors suggest that their list of quality indicators might be used as part of the assessment efforts in these healthcare systems.
Jayavani Moodley et al. investigated whether following quality recommendations actually improves patient outcomes. The 2007 American Association for the Study of Liver Disease and American College of Gastroenterology practice guidelines recommend screening and intervention to prevent esophageal varices in patients with cirrhosis. Moodley et al. studied whether there was an association between compliance with these guidelines and rate of esophageal variceal hemorrhage. In following 179 patients for almost 2 years, they associated physician compliance with a statistically significant reduction in first esophageal variceal hemorrhage. However, this study was performed at a tertiary care center that had a very high level of compliance, so the findings should be confirmed in community gastroenterology practices. The authors are planning investigate the patient, environment, and physician factors that contribute to noncompliance of guidelines.
In an accompanying editorial, Nezam Afdahl adds that with the increasing emphasis on quality assessment and quality-based reimbursement models, we need to find the best tools for assessing healthcare quality and for implementing guidelines. Moodley et al. adds that there needs to be increased awareness among healthcare providers about existing practice guidelines.
Kanwal F, Kramer J, Asch SM, et al. An explicit quality indicator set for measurement of quality of care in patients with cirrhosis. Clin Gastroenterol Hepatol 2010;8:709–717.
Moodley J, Lopez R, and Carey W. Compliance with practice guidelines and risk of a first esophageal variceal hemorrhage in patients with cirrhosis. Clin Gastroenterol Hepatol 2010;8:703–708.
Read the accompanying Editorial:
Lai M and Afdhal NH. Health care quality measurement in the care of patients with cirrhosis. Clin Gastroenterol Hepatol 2010;8:649–650.
Read the following related Comment from the Editor:
Volk ML, Piette JD, Singal AS, et al. Chronic disease management for patients with cirrhosis. Gastroenterology 2010;139: 14–16.
Source
Insurance companies and government agencies attempt to assess healthcare quality to develop quality-based reimbursement models. It is a challenge to define and measure quality of care, however, especially for complex, chronic diseases such as cirrhosis. Two studies in the August issue of Clinical Gastroenterology and Hepatology (CGH) identify tools for determining quality of care for patients with cirrhosis.
Fasiha Kanwal et al. identified quality indicators for treatment of patients with cirrhosis. A panel of 11 experts established a list of 41 quality indicators for 6 areas of care—ascites, variceal bleeding, hepatic encephalopathy, hepatocellular cancer, liver transplantation, and general cirrhosis care. In a related CGH podcast co-author Bruce Bacon describes the final 8 most important quality indicators selected by the panel. The authors conclude that this list begins to fill the void of quality assessment in cirrhosis; physicians might also use this list to identify processes in cirrhosis care that can be modified to improve patient outcomes. However, before this list is used in assessment processes, we must determine how adherence to this list of quality indicators actually affects outcomes. A better system to measure and track quality indicators also needs to be developed.
Hepatitis C-specific quality indicators have been implemented as part of the Medicare’s Physician Quality Reporting Initiative, a voluntary program that connects reimbursement incentive to compliance with performance using quality indicators. Kanwal et al. believe that with the increasing burden of cirrhosis, Medicare might extend the quality reporting initiatives to include the cirrhosis metrics, and that insurers will follow. The authors suggest that their list of quality indicators might be used as part of the assessment efforts in these healthcare systems.
Jayavani Moodley et al. investigated whether following quality recommendations actually improves patient outcomes. The 2007 American Association for the Study of Liver Disease and American College of Gastroenterology practice guidelines recommend screening and intervention to prevent esophageal varices in patients with cirrhosis. Moodley et al. studied whether there was an association between compliance with these guidelines and rate of esophageal variceal hemorrhage. In following 179 patients for almost 2 years, they associated physician compliance with a statistically significant reduction in first esophageal variceal hemorrhage. However, this study was performed at a tertiary care center that had a very high level of compliance, so the findings should be confirmed in community gastroenterology practices. The authors are planning investigate the patient, environment, and physician factors that contribute to noncompliance of guidelines.
Study population and screening endoscopy.
*Reasons for exclusion: previous diagnosis of EV, EVH or already treated with beta blockers. CCF, Cleveland Clinic Foundation.
Kanwal F, Kramer J, Asch SM, et al. An explicit quality indicator set for measurement of quality of care in patients with cirrhosis. Clin Gastroenterol Hepatol 2010;8:709–717.
Moodley J, Lopez R, and Carey W. Compliance with practice guidelines and risk of a first esophageal variceal hemorrhage in patients with cirrhosis. Clin Gastroenterol Hepatol 2010;8:703–708.
Read the accompanying Editorial:
Lai M and Afdhal NH. Health care quality measurement in the care of patients with cirrhosis. Clin Gastroenterol Hepatol 2010;8:649–650.
Read the following related Comment from the Editor:
Volk ML, Piette JD, Singal AS, et al. Chronic disease management for patients with cirrhosis. Gastroenterology 2010;139: 14–16.
Source
Stem cell, artificial liver research receives Coulter Foundation funding at NJIT
Public release date: 10-Aug-2010
Contact: Sheryl Weinstein
sheryl.m.weinstein@njit.edu
973-596-3436
New Jersey Institute of Technology
Two NJIT biomedical researchers have received the prestigious Coulter Foundation Translational Awards for promising patent applications that may some day extend peoples' lives.
The Coulter program provides funding for professors in established biomedical engineering departments within the U.S. Initial funding for each professor will be at least $200,000 over a two-year period.
NJIT Associate Professor Treena Arinzeh will receive funding for her patent application to create an electro-spun composite material for bone repair applications. Her composite material can be combined with stem cells to enhance the rate of bone repair.
NJIT Assistant Professor Cheul Cho will receive support for his patent application for an extracorporeal bio-artificial liver assist device with human stem cell-derived hepatocytes for the treatment of liver failure. His project aims to differentiate human embryonic stem (ES) cells into functional hepatocytes and to evaluate their therapeutic efficacy in a bio-artificial liver (BAL) for the treatment of acute liver failure. Current potential cell-based therapies and extracorporeal BAL devices for the treatment of liver failure are severely limited by the low availability of functional human liver cells, called hepatocytes.
Arinzeh's research focuses on tissue engineering, the application of principles and methods of engineering and life sciences toward a fundamental understanding and development of biological substitutes to restore, maintain and improve human tissue functions. Bone regeneration may be achieved by the use of osteogenic cells and/or factors to induce bone growth in combination with an appropriate scaffold to guide and support the laying down of new bone tissue.
Optimally, a scaffold for bone tissue engineering should satisfy the following minimum requirements, she said. It must be biocompatible, able to coexist with living tissues or organisms without causing harm. It must have osteoconductivity, able to serve as a scaffold or matrix on which bone cells may attach, migrate and form new bone. It should have minute openings, pores or holes, so that bone can grow inside the material. It should be biodegradable, able to break down in the body without causing harm. And, it should have mechanical integrity—the ability to hold together and withstand chemical, physical, and biological forces.
Cho's research focuses on designing a clinically-scaled bio-artificial liver. Approximately 10 percent of the liver mass is necessary to support a patient with acute liver failure, which is a critical limitation for many cell-based therapies for liver failure.
Embryonic stem cells are considered a potential source of cells for hepatic therapies due to their limitless capacity for self-renewal and proliferation, and their ability to differentiate into all major cell lineages.
Cho's novel method differentiates embryonic stem cells into hepatocytes with high purity. Incorporating these cell-derived hepatocytes into a device to treat fulminant hepatic failure has improved animal survival, thereby underscoring the cells' therapeutic potential. (A provisional patent was also filed for this project.)
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The Coulter Foundation supports biomedical research that is translational in nature, and it encourages and assists eligible biomedical engineering investigators to establish themselves in academic careers involving translational research. The translational research projects are directed at promising technologies with the goal of progressing toward commercial development and entering clinical practice.
NJIT, New Jersey's science and technology university,enrolls more than 8,800 students pursuing bachelor's, master's and doctoral degrees in 120 programs. The university consists of six colleges: Newark College of Engineering, College of Architecture and Design, College of Science and Liberal Arts, School of Management, College of Computing Sciences and Albert Dorman Honors College. U.S. News & World Report's 2009 Annual Guide to America's Best Colleges ranked NJIT in the top tier of national research universities. NJIT is internationally recognized for being at the edge in knowledge in architecture, applied mathematics, wireless communications and networking, solar physics, advanced engineered particulate materials, nanotechnology, neural engineering and e-learning. Many courses and certificate programs, as well as graduate degrees, are available online through the Office of Continuing Professional Education.
Source
Contact: Sheryl Weinstein
sheryl.m.weinstein@njit.edu
973-596-3436
New Jersey Institute of Technology
Two NJIT biomedical researchers have received the prestigious Coulter Foundation Translational Awards for promising patent applications that may some day extend peoples' lives.
The Coulter program provides funding for professors in established biomedical engineering departments within the U.S. Initial funding for each professor will be at least $200,000 over a two-year period.
NJIT Associate Professor Treena Arinzeh will receive funding for her patent application to create an electro-spun composite material for bone repair applications. Her composite material can be combined with stem cells to enhance the rate of bone repair.
NJIT Assistant Professor Cheul Cho will receive support for his patent application for an extracorporeal bio-artificial liver assist device with human stem cell-derived hepatocytes for the treatment of liver failure. His project aims to differentiate human embryonic stem (ES) cells into functional hepatocytes and to evaluate their therapeutic efficacy in a bio-artificial liver (BAL) for the treatment of acute liver failure. Current potential cell-based therapies and extracorporeal BAL devices for the treatment of liver failure are severely limited by the low availability of functional human liver cells, called hepatocytes.
Arinzeh's research focuses on tissue engineering, the application of principles and methods of engineering and life sciences toward a fundamental understanding and development of biological substitutes to restore, maintain and improve human tissue functions. Bone regeneration may be achieved by the use of osteogenic cells and/or factors to induce bone growth in combination with an appropriate scaffold to guide and support the laying down of new bone tissue.
Optimally, a scaffold for bone tissue engineering should satisfy the following minimum requirements, she said. It must be biocompatible, able to coexist with living tissues or organisms without causing harm. It must have osteoconductivity, able to serve as a scaffold or matrix on which bone cells may attach, migrate and form new bone. It should have minute openings, pores or holes, so that bone can grow inside the material. It should be biodegradable, able to break down in the body without causing harm. And, it should have mechanical integrity—the ability to hold together and withstand chemical, physical, and biological forces.
Cho's research focuses on designing a clinically-scaled bio-artificial liver. Approximately 10 percent of the liver mass is necessary to support a patient with acute liver failure, which is a critical limitation for many cell-based therapies for liver failure.
Embryonic stem cells are considered a potential source of cells for hepatic therapies due to their limitless capacity for self-renewal and proliferation, and their ability to differentiate into all major cell lineages.
Cho's novel method differentiates embryonic stem cells into hepatocytes with high purity. Incorporating these cell-derived hepatocytes into a device to treat fulminant hepatic failure has improved animal survival, thereby underscoring the cells' therapeutic potential. (A provisional patent was also filed for this project.)
###
The Coulter Foundation supports biomedical research that is translational in nature, and it encourages and assists eligible biomedical engineering investigators to establish themselves in academic careers involving translational research. The translational research projects are directed at promising technologies with the goal of progressing toward commercial development and entering clinical practice.
NJIT, New Jersey's science and technology university,enrolls more than 8,800 students pursuing bachelor's, master's and doctoral degrees in 120 programs. The university consists of six colleges: Newark College of Engineering, College of Architecture and Design, College of Science and Liberal Arts, School of Management, College of Computing Sciences and Albert Dorman Honors College. U.S. News & World Report's 2009 Annual Guide to America's Best Colleges ranked NJIT in the top tier of national research universities. NJIT is internationally recognized for being at the edge in knowledge in architecture, applied mathematics, wireless communications and networking, solar physics, advanced engineered particulate materials, nanotechnology, neural engineering and e-learning. Many courses and certificate programs, as well as graduate degrees, are available online through the Office of Continuing Professional Education.
Source
Drug Resistance Linked to Faster Hepatitis B Liver Disease Progression in HIV/HBV Coinfected Patients
SUMMARY: HIV/HBV coinfected individuals may be less likely to have hepatitis B virus (HBV) with mutations conferring resistance to lamivudine (3TC; Epivir), but those who do have drug resistance experience faster liver disease progression and are more likely to develop cirrhosis, according to a study from Romania presented last month at the XVIII International AIDS Conference (AIDS 2010) in Vienna.
By Liz Highleyman
Over years or decades, chronic hepatitis B can lead to advanced liver disease including cirrhosis and hepatocellular carcinoma (HCC). Research suggests that this progression happens more rapidly in HIV/HBV coinfected people compared with HIV negative individuals, but effective antiretroviral therapy (ART) may slow the process. A number of drugs used in ART -- including lamivudine, emtricitabine (Emtriva), and tenofovir (Viread) -- are active against both HIV and HBV.
Irina Magdalena from Dumitru Ovidius University in Constanta, Romania, and colleagues looked at the long-term evolution of liver disease among coinfected patients receiving combination ART.
The prospective observation cohort study included 72 HIV/HBV coinfected participants who did not show signs of liver disease at baseline. This group was unlike most US and European HIV cohorts in that just over half (54%) were men and the median age was only 29 years. The median CD4 cell count was low, at 230 cells/mm3. About two-thirds were hepatitis B "e" antigen (HBeAg) negative; none had hepatitis C or D.
Participants were followed for a period of 5 years on ART, and all were taking combination regimens containing a ritonavir-boosted protease inhibitor. Clinical and virological data were collected every 3-6 months and ultrasound imaging was done annually to monitor for liver cancer; FibroScan (transient elastometry) was performed during the last year. All patients with detectable serum HBV DNA viral load were tested for HBV drug resistance.
Results
--2 cases of hepatocellular carcinoma;
--1 case of fulminant hepatitis.
"Appropriate monitoring of chronic viral hepatitis B in HIV positive patients include[s] the recognition of lamivudine resistance in every case of detectable HBV DNA level," they recommended.
Ovidius University Constanta, Faculty of Medicine, Constanta, Romania; Clinical Infectious Diseases Hospital, Constanta, Romania.
8/10/10
Reference
IM Dumitru, E Dumitru, S Rugina, and others. HBV related complications in HIV positive patients during HAART therapy. XVIII International AIDS Conference (AIDS 2010). Vienna, July 18-23, 2010. (Abstract).
Source
By Liz Highleyman
Over years or decades, chronic hepatitis B can lead to advanced liver disease including cirrhosis and hepatocellular carcinoma (HCC). Research suggests that this progression happens more rapidly in HIV/HBV coinfected people compared with HIV negative individuals, but effective antiretroviral therapy (ART) may slow the process. A number of drugs used in ART -- including lamivudine, emtricitabine (Emtriva), and tenofovir (Viread) -- are active against both HIV and HBV.
Irina Magdalena from Dumitru Ovidius University in Constanta, Romania, and colleagues looked at the long-term evolution of liver disease among coinfected patients receiving combination ART.
The prospective observation cohort study included 72 HIV/HBV coinfected participants who did not show signs of liver disease at baseline. This group was unlike most US and European HIV cohorts in that just over half (54%) were men and the median age was only 29 years. The median CD4 cell count was low, at 230 cells/mm3. About two-thirds were hepatitis B "e" antigen (HBeAg) negative; none had hepatitis C or D.
Participants were followed for a period of 5 years on ART, and all were taking combination regimens containing a ritonavir-boosted protease inhibitor. Clinical and virological data were collected every 3-6 months and ultrasound imaging was done annually to monitor for liver cancer; FibroScan (transient elastometry) was performed during the last year. All patients with detectable serum HBV DNA viral load were tested for HBV drug resistance.
Results
- While no patients had signs of liver disease at the beginning of the study, 8 of 72 (11%) had advanced disease after 5 years of follow-up:
--2 cases of hepatocellular carcinoma;
--1 case of fulminant hepatitis.
- All patients with advanced liver disease had high serum HBV DNA but undetectable HIV.
- All had lamivudine resistance (mutations M204V, M204I, L180M, L80I).
- 5 of these 8 patients died.
- The remaining 64 patients had no signs of active liver disease, with ALT levels normal or < 2 x upper limit of normal and fibrosis stage F0-F1 (absent to mild) according to Fibroscan.
- Among patients without advanced liver disease, 10 had lamivudine resistance.
"Appropriate monitoring of chronic viral hepatitis B in HIV positive patients include[s] the recognition of lamivudine resistance in every case of detectable HBV DNA level," they recommended.
Ovidius University Constanta, Faculty of Medicine, Constanta, Romania; Clinical Infectious Diseases Hospital, Constanta, Romania.
8/10/10
Reference
IM Dumitru, E Dumitru, S Rugina, and others. HBV related complications in HIV positive patients during HAART therapy. XVIII International AIDS Conference (AIDS 2010). Vienna, July 18-23, 2010. (Abstract).
Source
Vertex: At the Finish Line for a Hepatitis C Cure
August 10, 2010
When an investigational drug proves it can eradicate a virus we call it a breakthrough. The nearest to approval of the expected breakthroughs is Vertex’s (VRTX) drug telaprevir, a specific hepatitis C virus protease inhibitor. The drug was a blessing for the infected victims who had it in clinical trials. It brought a miracle happy ending to what seemed to be an endless nightmare of acute liver inflammation, chronic liver inflammation, liver cirrhosis, liver transplant and possible liver cancer. We expected telaprevir to be greeted positively by the government and insurance companies, which spend tons of money on the HCV liver problems where treatments that do not work are, nevertheless, paid for.
More than anybody else, we expected they would cheer the news about the successful outcome of telaprevir in clearing the virus in large clinical trials. We were confident that they will not overlook Vertex's drug importance, its huge market and the fact that it is expected to be the first approved protease inhibitor, i.e., the first approved drug to that deals with the virus itself, not only its symptoms. We thought they would rush to buy VRTX as undervalued as it is and as it has constantly been for the past three years. Surprisingly enough, investors seemed uninterested in the $10 B market and, instead of buying the stock, they kept trading up and down, but to the negative side. The reason, as we see it, is that investors believe that the real influence on stock pricing comes not from the firms’ good news, or expected huge revenues and sales growth, but from emperors who dictate the prices of the publicly-traded firms.
To investors we say: Few firms have very effective weapons against HCV. Only two of them will get their drugs on the market in 2011. Vertex’s HCV drug telaprevir will be the first HCV specific protease inhibitor to offer a real hops for a hepatitis C cure. The virus has infected roughly four million Americans, most of them baby boomers, in addition to 170 million people worldwide. You can imagine how large the market is. About 12,000 Americans infected with HCV develop cirrhosis every year - a number that will continue to rise in the coming decade. Some negative traders perpetrate the fact that the number of newly diagnosed cases is dropping. This reality, though, would not affect the new drug sales, as hundreds of thousands of people who were infected decades ago are expected to begin experiencing disagreeable complications and liver damage and are anxious to get the drug that would protect them from a miserable future with liver cirrhosis, possible liver failure, liver transplant and possible liver cancer.
Clinical trial results demonstrate that telaprevir has, indeed, cleared the virus from the bloodstream of infected patients and achieved a sustained viral response (SVR). Data from a late-stage clinical trial demonstrated that a combination telaprevir/alpha interferon/ribavirin was capable of effectively curing 75 percent of patients, compared with 44 percent of those treated with the same drugs but without telaprevir. According to an article written in the New York Times, a doctor who works as a consultant to some pharmaceutical companies said that one-fifth of his patients were being “warehoused,” meaning they were forgoing treatment now to wait for the new drugs. The number of infected patients as mentioned above might be misleading as it seems that 75% of the infected patients have no clue that they are infected, as they have never been tested for HCV. Now, drug companies and the government are doing a great job raising awareness about HCV infection. Recently, the FDA approved a rapid blood test developed by Orasure Technologies that can provide results in minutes.
The current treatment for hepatitis C consists of weekly injections of alpha interferon and ribavirin. While nobody knows how these drugs work, telaprevir is known to inhibit the protease enzyme required by HCV virus, similar to the HIV new drugs.
Following the approval of telaprevir, which is expected in early 2011, Merck’s (MRK) drug, boceprevir, would probably be available a few months later. The market is huge and more drugs in this category are required to satisfy its needs. Around half a million people feel lucky as the drugs will save them after other drugs stopped helping them. People who had to take drugs derived from human plasma years ago are now facing the complications of HCV. They are in bad need for drug combination, which includes protease inhibitors.
Vertex said it remains on track to complete the New Drug Application submission process for telaprevir later this year and to complete the build-out of its commercial function in advance of the potential launch of telaprevir. A rolling application allows the company to submit pieces of data as they become available. Vertex says the application will be complete this year.
Data from two more phase 3 trials are expected in the next couple of months. Common sense dictates that these data must boost the stock, but reality on Wall Street tells us that people have eyes but do not see and ears that do not hear. That’s why we have a plan B, which is to consider any selling of VRTX a unique opportunity to buy the stock at a bargain price.
Are you listening?
Other small biotech developing HCV drugs: Idenix (IDIX); Anadys (ANDS), Intermune (ITMN) and Dynavax (DVAX).
Disclosure: long Vertex
About the author: Prohost Biotech
The enormous advancement in the biological sciences that is taking place has begun to change the traditional way of practicing medicine. Far-reaching biological products are being approved and news about breakthroughs are occupying the headlines. However, selecting the biotechnology firms in...More
Company: Prohost Biotech
Blog: prohostbiotech.com
Source
When an investigational drug proves it can eradicate a virus we call it a breakthrough. The nearest to approval of the expected breakthroughs is Vertex’s (VRTX) drug telaprevir, a specific hepatitis C virus protease inhibitor. The drug was a blessing for the infected victims who had it in clinical trials. It brought a miracle happy ending to what seemed to be an endless nightmare of acute liver inflammation, chronic liver inflammation, liver cirrhosis, liver transplant and possible liver cancer. We expected telaprevir to be greeted positively by the government and insurance companies, which spend tons of money on the HCV liver problems where treatments that do not work are, nevertheless, paid for.
More than anybody else, we expected they would cheer the news about the successful outcome of telaprevir in clearing the virus in large clinical trials. We were confident that they will not overlook Vertex's drug importance, its huge market and the fact that it is expected to be the first approved protease inhibitor, i.e., the first approved drug to that deals with the virus itself, not only its symptoms. We thought they would rush to buy VRTX as undervalued as it is and as it has constantly been for the past three years. Surprisingly enough, investors seemed uninterested in the $10 B market and, instead of buying the stock, they kept trading up and down, but to the negative side. The reason, as we see it, is that investors believe that the real influence on stock pricing comes not from the firms’ good news, or expected huge revenues and sales growth, but from emperors who dictate the prices of the publicly-traded firms.
To investors we say: Few firms have very effective weapons against HCV. Only two of them will get their drugs on the market in 2011. Vertex’s HCV drug telaprevir will be the first HCV specific protease inhibitor to offer a real hops for a hepatitis C cure. The virus has infected roughly four million Americans, most of them baby boomers, in addition to 170 million people worldwide. You can imagine how large the market is. About 12,000 Americans infected with HCV develop cirrhosis every year - a number that will continue to rise in the coming decade. Some negative traders perpetrate the fact that the number of newly diagnosed cases is dropping. This reality, though, would not affect the new drug sales, as hundreds of thousands of people who were infected decades ago are expected to begin experiencing disagreeable complications and liver damage and are anxious to get the drug that would protect them from a miserable future with liver cirrhosis, possible liver failure, liver transplant and possible liver cancer.
Clinical trial results demonstrate that telaprevir has, indeed, cleared the virus from the bloodstream of infected patients and achieved a sustained viral response (SVR). Data from a late-stage clinical trial demonstrated that a combination telaprevir/alpha interferon/ribavirin was capable of effectively curing 75 percent of patients, compared with 44 percent of those treated with the same drugs but without telaprevir. According to an article written in the New York Times, a doctor who works as a consultant to some pharmaceutical companies said that one-fifth of his patients were being “warehoused,” meaning they were forgoing treatment now to wait for the new drugs. The number of infected patients as mentioned above might be misleading as it seems that 75% of the infected patients have no clue that they are infected, as they have never been tested for HCV. Now, drug companies and the government are doing a great job raising awareness about HCV infection. Recently, the FDA approved a rapid blood test developed by Orasure Technologies that can provide results in minutes.
The current treatment for hepatitis C consists of weekly injections of alpha interferon and ribavirin. While nobody knows how these drugs work, telaprevir is known to inhibit the protease enzyme required by HCV virus, similar to the HIV new drugs.
Following the approval of telaprevir, which is expected in early 2011, Merck’s (MRK) drug, boceprevir, would probably be available a few months later. The market is huge and more drugs in this category are required to satisfy its needs. Around half a million people feel lucky as the drugs will save them after other drugs stopped helping them. People who had to take drugs derived from human plasma years ago are now facing the complications of HCV. They are in bad need for drug combination, which includes protease inhibitors.
Vertex said it remains on track to complete the New Drug Application submission process for telaprevir later this year and to complete the build-out of its commercial function in advance of the potential launch of telaprevir. A rolling application allows the company to submit pieces of data as they become available. Vertex says the application will be complete this year.
Data from two more phase 3 trials are expected in the next couple of months. Common sense dictates that these data must boost the stock, but reality on Wall Street tells us that people have eyes but do not see and ears that do not hear. That’s why we have a plan B, which is to consider any selling of VRTX a unique opportunity to buy the stock at a bargain price.
Are you listening?
Other small biotech developing HCV drugs: Idenix (IDIX); Anadys (ANDS), Intermune (ITMN) and Dynavax (DVAX).
Disclosure: long Vertex
About the author: Prohost Biotech
The enormous advancement in the biological sciences that is taking place has begun to change the traditional way of practicing medicine. Far-reaching biological products are being approved and news about breakthroughs are occupying the headlines. However, selecting the biotechnology firms in...More
Company: Prohost Biotech
Blog: prohostbiotech.com
Source
Chronic hepatitis C infection blunts CD4 gains after start of HIV treatment
Hepatitis and HIV
Michael Carter
Published: 10 August 2010
Ongoing hepatitis C replication inhibits improvements in the CD4 cell counts of HIV-positive patients taking antiretroviral therapy, Canadian investigators report in the July 31stedition of AIDS.
Researchers monitored changes in the CD4 cell counts of HIV-positive patients who had antibodies to hepatitis C virus. Falls in CD4 cell counts before HIV treatment was started, and increases in such counts after the initiation of antiretroviral therapy were compared between individuals who had spontaneously cleared hepatitis C, and those who had chronic infection with the virus.
Ongoing hepatitis C replication was associated with slightly higher CD4 cell count loss prior to starting HIV treatment. There was also clear evidence that individuals with chronic hepatitis C had blunted CD4 cell responses to antiretroviral therapy.
“Spontaneous clearance of HCV [hepatitis C virus] is independently associated with a better rate of CD4 cell recovery once ART [antiretroviral therapy] is introduced”, comment the investigators, who stress that their “findings were robust.”
Investigators from the Canadian Coinfection Cohort Study performed their research because there is uncertainty about the impact of hepatitis C co-infection on HIV disease progression. Moreover, they were concerned that earlier research exploring this question may have been limited because antibody status was used to define hepatitis C infection. A significant proportion of patients infected with hepatitis C spontaneously clear the infection, leading the researchers to postulate that the results of some studies could have been confounded because some individuals in the hepatitis C arm were in fact free from the infection.
Their study population included 271 patients. All were infected with HIV, and all had antibodies to hepatitis C.
However, they divided the patients into two groups. The first involved 236 with chronic hepatitis C infection (and therefore ongoing replication of the virus), the other, those who had spontaneously cleared the infection.
Changes in the CD4 cell counts of these two groups were then compared before and after the initiation of antiretroviral therapy.
A total of 95 patients, 25 of whom had spontaneously cleared hepatitis C, were naïve to HIV treatment on recruitment to the study.
CD4 cell counts fell by a non-significant average of 44 cells/mm3 per year amongst the patients who had cleared hepatitis C, and by an average of 84 cells/mm3each year in those with ongoing replication of the virus. However, after adjustment for follow-up time the association between chronic hepatitis C infection and greater loss of CD4 cells was not significant.
Information on CD4 cell count increases after the initiation of antiretroviral therapy was available for 226 individuals. Once again, 25 patients had spontaneously cleared their hepatitis C infection. The median duration of follow-up was 18 months for those with chronic hepatitis C and 15 months for those who had cleared the infection.
Average annual CD4 cell count increases were seven-fold higher for patients who had cleared hepatitis C infection than for those with ongoing hepatitis C replication (4 vs. 24 cells/mm3 p < 0.001).
The association between spontaneous clearance of hepatitis C virus and more robust increases in CD4 cell count during HIV therapy remained significant after the investigators adjusted their results to take into account potentially confounding factors.
Moreover, the researchers also founded that the blunted CD4 cell response seen in the patients with chronic hepatitis C did not improve over time.
Limiting analysis to patients who started HIV treatment for the first time after entry to the study cohort did not affect the results.
However, when the researchers restricted their analysis to patients who maintained an undetectable HIV viral load throughout follow-up, the impact of chronic hepatitis C virus infection on CD4 cell count recovery was attenuated. CD4 cell counts still increased more slowly in those with ongoing replication of hepatitis C, but the interaction between chronic infection and CD4 cell gain ceased to be statistically significant.
“We found that CD4 cell progression is negatively affected by the presence of ongoing HCV replication in coinfected individuals taking ART”, write the investigators. They add, “elucidating the mechanisms by which this difference occurs and investigating the impact of HCV treatment on CD4 cell progression should be prioritised.”
The study’s authors conclude, “when successful, HCV treatment might have an important role not only in improving HCV related outcomes, but for HIV-related prognosis as well”.
Reference
Potter M et al. Impact of hepatitis C viral replication on CD4 T-lymphocyte progression in HIV – HCV coinfection before and after antiretroviral therapy. AIDS 24: 1857-65, 2010.
Source
Michael Carter
Published: 10 August 2010
Ongoing hepatitis C replication inhibits improvements in the CD4 cell counts of HIV-positive patients taking antiretroviral therapy, Canadian investigators report in the July 31stedition of AIDS.
Researchers monitored changes in the CD4 cell counts of HIV-positive patients who had antibodies to hepatitis C virus. Falls in CD4 cell counts before HIV treatment was started, and increases in such counts after the initiation of antiretroviral therapy were compared between individuals who had spontaneously cleared hepatitis C, and those who had chronic infection with the virus.
Ongoing hepatitis C replication was associated with slightly higher CD4 cell count loss prior to starting HIV treatment. There was also clear evidence that individuals with chronic hepatitis C had blunted CD4 cell responses to antiretroviral therapy.
“Spontaneous clearance of HCV [hepatitis C virus] is independently associated with a better rate of CD4 cell recovery once ART [antiretroviral therapy] is introduced”, comment the investigators, who stress that their “findings were robust.”
Investigators from the Canadian Coinfection Cohort Study performed their research because there is uncertainty about the impact of hepatitis C co-infection on HIV disease progression. Moreover, they were concerned that earlier research exploring this question may have been limited because antibody status was used to define hepatitis C infection. A significant proportion of patients infected with hepatitis C spontaneously clear the infection, leading the researchers to postulate that the results of some studies could have been confounded because some individuals in the hepatitis C arm were in fact free from the infection.
Their study population included 271 patients. All were infected with HIV, and all had antibodies to hepatitis C.
However, they divided the patients into two groups. The first involved 236 with chronic hepatitis C infection (and therefore ongoing replication of the virus), the other, those who had spontaneously cleared the infection.
Changes in the CD4 cell counts of these two groups were then compared before and after the initiation of antiretroviral therapy.
A total of 95 patients, 25 of whom had spontaneously cleared hepatitis C, were naïve to HIV treatment on recruitment to the study.
CD4 cell counts fell by a non-significant average of 44 cells/mm3 per year amongst the patients who had cleared hepatitis C, and by an average of 84 cells/mm3each year in those with ongoing replication of the virus. However, after adjustment for follow-up time the association between chronic hepatitis C infection and greater loss of CD4 cells was not significant.
Information on CD4 cell count increases after the initiation of antiretroviral therapy was available for 226 individuals. Once again, 25 patients had spontaneously cleared their hepatitis C infection. The median duration of follow-up was 18 months for those with chronic hepatitis C and 15 months for those who had cleared the infection.
Average annual CD4 cell count increases were seven-fold higher for patients who had cleared hepatitis C infection than for those with ongoing hepatitis C replication (4 vs. 24 cells/mm3 p < 0.001).
The association between spontaneous clearance of hepatitis C virus and more robust increases in CD4 cell count during HIV therapy remained significant after the investigators adjusted their results to take into account potentially confounding factors.
Moreover, the researchers also founded that the blunted CD4 cell response seen in the patients with chronic hepatitis C did not improve over time.
Limiting analysis to patients who started HIV treatment for the first time after entry to the study cohort did not affect the results.
However, when the researchers restricted their analysis to patients who maintained an undetectable HIV viral load throughout follow-up, the impact of chronic hepatitis C virus infection on CD4 cell count recovery was attenuated. CD4 cell counts still increased more slowly in those with ongoing replication of hepatitis C, but the interaction between chronic infection and CD4 cell gain ceased to be statistically significant.
“We found that CD4 cell progression is negatively affected by the presence of ongoing HCV replication in coinfected individuals taking ART”, write the investigators. They add, “elucidating the mechanisms by which this difference occurs and investigating the impact of HCV treatment on CD4 cell progression should be prioritised.”
The study’s authors conclude, “when successful, HCV treatment might have an important role not only in improving HCV related outcomes, but for HIV-related prognosis as well”.
Reference
Potter M et al. Impact of hepatitis C viral replication on CD4 T-lymphocyte progression in HIV – HCV coinfection before and after antiretroviral therapy. AIDS 24: 1857-65, 2010.
Source
Phase 3 ILLUMINATE Study Supports 24-Week Telaprevir-Based Therapy Within a Response-Guided Regimen for People with Hepatitis C Who Had Not Received Prior Treatment
-Viral cure rates of 92% and 88% with 24 and 48-week regimens, respectively, in people who met certain response criteria-
CAMBRIDGE, Mass., Aug 10, 2010 (BUSINESS WIRE) -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced results from the Phase 3 ILLUMINATE study, which was designed to evaluate whether there was any benefit to extending therapy from 24 to 48 weeks in people whose hepatitis C virus (HCV) was undetectable at weeks 4 and 12 of treatment (extended rapid viral response or eRVR). People in the trial who met these eRVR criteria and who remained on treatment were then randomized at week 20 to receive 24 or 48 weeks of total treatment. People who did not meet these criteria were assigned to 48 weeks of pegylated-interferon and ribavirin therapy.
Sustained viral response (SVR or viral cure) rates of 92% and 88% were observed in the randomized 24 and 48-week telaprevir-based treatment groups, respectively. 72% of all 540 people treated with telaprevir in the study achieved a viral cure. The safety and tolerability profile of the telaprevir-based regimen was consistent with results reported previously from the pivotal Phase 3 ADVANCE study.
"The viral cure rates seen in ILLUMINATE showed that there was no benefit to extending telaprevir-based therapy to 48 weeks for the majority of people," said Kenneth Sherman, M.D., Ph.D., Professor of Medicine at the University of Cincinnati College of Medicine, Director of the Division of Digestive Diseases for UC Health and Principal Investigator of the trial. "Patients who had a rapid response to telaprevir-based regimens at weeks 4 and 12 had a high likelihood of achieving a cure with 24 weeks of total treatment, which may provide important information to motivate people to continue therapy."
"Data from ILLUMINATE and ADVANCE support our belief that the use of 24-week telaprevir-based therapy within a response-guided regimen may provide an important future treatment option for people with hepatitis C," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex.
Telaprevir is an investigational, oral inhibitor of HCV protease, an enzyme essential for viral replication, and is being developed by Vertex Pharmaceuticals in collaboration with Tibotec Pharmaceuticals and Mitsubishi Tanabe Pharma. Results from the ILLUMINATE study are expected to supplement data obtained from ADVANCE and REALIZE - the two pivotal Phase 3 studies of telaprevir - as part of a New Drug Application submission to the U.S. Food and Drug Administration planned for the fourth quarter of 2010.
Efficacy Results from ILLUMINATE
Primary analysis for people who met certain response criteria*:
24-week telaprevir-based treatment regimen:
Overall efficacy analysis for all patients treated with telaprevir in ILLUMINATE (ITT or intent-to-treat analysis):
The safety and tolerability profile of the telaprevir-based regimen in the ILLUMINATE study was similar to results reported from the Phase 3 ADVANCE study. The most common adverse events reported in the ILLUMINATE study, in order of frequency, were fatigue, pruritus, nausea, anemia, rash and headache. The majority of these adverse events were mild or moderate. Adverse events leading to discontinuation of all study drugs during the 12-week telaprevir dosing period occurred in 6.9% of people in the study. Treatment discontinuation of all drugs due to anemia and rash occurred in 1.1% and 0.6% of people in the study, respectively, during the telaprevir dosing period. Like in ADVANCE, the use of erythropoiesis-stimulating agents (ESAs) was not allowed in this study.
Data from ILLUMINATE have been submitted for presentation at the 2010 Annual Meeting of the American Association for the Study of Liver Diseases.
About the ILLUMINATE Trial
ILLUMINATE was a Phase 3, supplemental, open-label, randomized study in people infected with genotype 1 chronic hepatitis C, the most common form of the virus in the U.S. and Europe, who had not been previously treated (treatment-naïve). In this study, people who met protocol-defined response criteria of achieving eRVR were randomized at week 20 to receive 24 or 48 weeks of total treatment. The primary endpoint of the study was the proportion of patients who achieved SVR in the randomized treatment groups, and evaluated by a non-inferiority analysis. Based on this analysis, the study achieved its primary endpoint of non-inferiority with respect to SVR rates in the randomized 24 and 48-week telaprevir-based arms. The trial enrolled people at 76 clinical trial sites in the U.S. and Europe. A greater proportion of people in the ILLUMINATE study (approximately 90%) were enrolled at U.S. sites compared to the proportion in ADVANCE. As in all studies evaluating telaprevir-based regimens, patients received no more than 12 weeks of triple therapy (telaprevir, pegylated-interferon and ribavirin) followed by pegylated-interferon and ribavirin only, as part of either 24 or 48 weeks of total treatment, as noted in the trial design.
About the Telaprevir Development Program
To date, more than 2,500 people with hepatitis C have received telaprevir-based therapy as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE trials. Together, these studies enrolled people with genotype 1 hepatitis C who had not been treated for their disease previously as well as people who had been treated before but did not achieve a viral cure. The telaprevir clinical development program is the largest conducted to date for any investigational direct-acting antiviral hepatitis C therapy.
Phase 3 ADVANCE Trial
The pivotal Phase 3 ADVANCE study evaluated telaprevir-based response-guided regimens in 1,095 treatment-naïve patients. Data from this trial has been accepted for presentation at the 2010 Annual Meeting of the American Association for the Study of Liver Diseases.
Phase 3 REALIZE Trial
The second pivotal Phase 3 study, REALIZE, which is being conducted by Vertex's collaborator Tibotec, is evaluating telaprevir-based regimens in approximately 650 people who did not achieve a viral cure with a prior pegylated-interferon based treatment. REALIZE is the only current Phase 3 study of an investigational hepatitis C therapy to enroll a difficult-to-treat population that includes patients who had a null response and failed to achieve a viral cure with a prior course of hepatitis C therapy. Topline data from REALIZE are expected in September 2010.
Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
About Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the blood of people with the disease.2 According to a 2010 report from the Institute of Medicine, up to 3.9 million people in the United States have chronic hepatitis C and 75% of those infected are unaware of it.3 Approximately 60 percent of genotype 1 patients who undergo an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved treatment regimen, do not achieve a SVR 4,5,6 or viral cure.1
Hepatitis C is spread through direct contact with the blood of infected people.2 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.2 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure, or liver cancer.2 If treatment is not successful and a person does not achieve a viral cure, they remain at risk for progressive liver disease.7,8,9,10,11 In the United States, hepatitis C is the leading cause of liver transplantations and is reported to contribute to 4,600 to 12,000 deaths annually.8 The majority of people with hepatitis C were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.11 Over the next 20 years, total annual medical costs for people with hepatitis C are expected to more than double, from $30 billion today to approximately $85 billion.11
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer, and pain.
--Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
--Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
Additional resources for media, including a hepatitis C backgrounder and glossary of common terms, are available at: http://investors.vrtx.com/press.cfm
References:
1 Ghany, m.G., Strader, d.B., Thomas, d.L., Seeff, Leondard B. diagnosis, management and Treatment of Hepatitis C; An Update. 2009. Hepatology. 2009;49 (4):1-40.
2 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at:
http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed May 25, 2010.
3 Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Available at http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Accessed May 25, 2010.
4 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
5 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
6 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
7 Morgan T.R, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
8 Davis, G.L., Alter, M. J. , El-Serag, H. Clinical-Liver, Pancreas, and Biliary Tract. Journal of Gastroenterology. 2010;138: 513-521.
9 Volk, Michael I., Tocco, Rachel, Saini, Sameer, Lok, Anna S.F. Public Health Impact of Antiviral Therapy for Hepatitis C in the United States. Hepatology.2009;50(6):1750-1755.
10 Veldt, B.J., Heathcote, J., Wedmeyer, H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
11 Pyenson, B., Fitch, K., Iwasaki, K. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Milliman, Inc. This report was commissioned by Vertex Pharmaceuticals, Inc. May, 2009.
Special Note Regarding Forward-looking Statements
This press release contains forward-looking statements, including statements regarding (i) the potential importance of the ILLUMINATE results as described above by Drs. Sherman and Kauffman, (ii) data from ILLUMINATE supporting 24-week telaprevir-based therapy within a response-guided regimen, (iii) the expectation that results from ILLUMINATE will supplement data obtained from ADVANCE and REALIZE, (iv) the planed submission of a New Drug Application for telaprevir in the fourth quarter of 2010 and (v) the expectation that topline data from REALIZE will be available in September 2010. While the Company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that future outcomes from clinical trials of telaprevir (including the REALIZE clinical trial) may not be favorable or may be less favorable than the outcomes reported from ILLUMINATE, ADVANCE and earlier clinical trials of telaprevir; that the Company could experience unforeseen delays in submitting the NDA for telaprevir and/or obtaining approval to market telaprevir; that there may be varying interpretations of the data from the telaprevir clinical trials; and that future scientific, clinical, competitive or other market factors may adversely affect the potential for telaprevir-based combination therapy and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the Company's website at www.vrtx.com. The Company disclaims any obligation to update the information contained in this press release as new information becomes available.
Vertex Pharmaceuticals will host a conference call on Tuesday, August 10, 2010 at 8:30 a.m. ET to review recent developments. To listen to the call on the telephone, dial 888-466-4587 (U.S. and Canada) or 719-325-2180 (International) and the conference ID number is 6448142. Vertex is also providing a podcast MP3 file available for download on the Vertex website at http://www.vrtx.com/.
The call will be available for replay via telephone commencing August 10, 2010 at 12:00 p.m. ET running through 5:00 p.m. on August 24, 2010. The replay phone number for the U.S. and Canada is 888-203-1112. The international replay number is 719-457-0820 and the conference ID number is 6448142. Following the live webcast, an archived version will be available on Vertex's website until 5:00 p.m. on August 17, 2010.
(VRTX-GEN)
Photos/Multimedia Gallery Available: http://www.businesswire.com/cgi-bin/mmg.cgi?eid=6391442&lang=en
SOURCE: Vertex Pharmaceuticals Incorporated
Vertex Pharmaceuticals Incorporated
Media:
Amy Pasqua, 617-444-6992
or
Megan Pace, 617-444-6992
or
Investors:
Michael Partridge, 617-444-6108
or
Lora Pike, 617-444-6755
*Received in email update from Vertex*
-Safety and tolerability results were similar to those seen in the Phase 3 ADVANCE study-
CAMBRIDGE, Mass., Aug 10, 2010 (BUSINESS WIRE) -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced results from the Phase 3 ILLUMINATE study, which was designed to evaluate whether there was any benefit to extending therapy from 24 to 48 weeks in people whose hepatitis C virus (HCV) was undetectable at weeks 4 and 12 of treatment (extended rapid viral response or eRVR). People in the trial who met these eRVR criteria and who remained on treatment were then randomized at week 20 to receive 24 or 48 weeks of total treatment. People who did not meet these criteria were assigned to 48 weeks of pegylated-interferon and ribavirin therapy.
Sustained viral response (SVR or viral cure) rates of 92% and 88% were observed in the randomized 24 and 48-week telaprevir-based treatment groups, respectively. 72% of all 540 people treated with telaprevir in the study achieved a viral cure. The safety and tolerability profile of the telaprevir-based regimen was consistent with results reported previously from the pivotal Phase 3 ADVANCE study.
"The viral cure rates seen in ILLUMINATE showed that there was no benefit to extending telaprevir-based therapy to 48 weeks for the majority of people," said Kenneth Sherman, M.D., Ph.D., Professor of Medicine at the University of Cincinnati College of Medicine, Director of the Division of Digestive Diseases for UC Health and Principal Investigator of the trial. "Patients who had a rapid response to telaprevir-based regimens at weeks 4 and 12 had a high likelihood of achieving a cure with 24 weeks of total treatment, which may provide important information to motivate people to continue therapy."
"Data from ILLUMINATE and ADVANCE support our belief that the use of 24-week telaprevir-based therapy within a response-guided regimen may provide an important future treatment option for people with hepatitis C," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex.
Telaprevir is an investigational, oral inhibitor of HCV protease, an enzyme essential for viral replication, and is being developed by Vertex Pharmaceuticals in collaboration with Tibotec Pharmaceuticals and Mitsubishi Tanabe Pharma. Results from the ILLUMINATE study are expected to supplement data obtained from ADVANCE and REALIZE - the two pivotal Phase 3 studies of telaprevir - as part of a New Drug Application submission to the U.S. Food and Drug Administration planned for the fourth quarter of 2010.
Efficacy Results from ILLUMINATE
Primary analysis for people who met certain response criteria*:
24-week telaprevir-based treatment regimen:
- SVR Rate: 92% (149/162)
- Relapse Rate: 5.7% (9/159)
- SVR Rate: 88% (140/160)
- Relapse Rate: 1.9% (3/154)
Overall efficacy analysis for all patients treated with telaprevir in ILLUMINATE (ITT or intent-to-treat analysis):
- SVR Rate: 72% (388/540)
- Relapse Rate: 7.7% (36/469)
- Rapid Viral Response (RVR) Rate: 72% (389/540)
- Extended RVR (eRVR): 65% (352/540)
The safety and tolerability profile of the telaprevir-based regimen in the ILLUMINATE study was similar to results reported from the Phase 3 ADVANCE study. The most common adverse events reported in the ILLUMINATE study, in order of frequency, were fatigue, pruritus, nausea, anemia, rash and headache. The majority of these adverse events were mild or moderate. Adverse events leading to discontinuation of all study drugs during the 12-week telaprevir dosing period occurred in 6.9% of people in the study. Treatment discontinuation of all drugs due to anemia and rash occurred in 1.1% and 0.6% of people in the study, respectively, during the telaprevir dosing period. Like in ADVANCE, the use of erythropoiesis-stimulating agents (ESAs) was not allowed in this study.
Data from ILLUMINATE have been submitted for presentation at the 2010 Annual Meeting of the American Association for the Study of Liver Diseases.
About the ILLUMINATE Trial
ILLUMINATE was a Phase 3, supplemental, open-label, randomized study in people infected with genotype 1 chronic hepatitis C, the most common form of the virus in the U.S. and Europe, who had not been previously treated (treatment-naïve). In this study, people who met protocol-defined response criteria of achieving eRVR were randomized at week 20 to receive 24 or 48 weeks of total treatment. The primary endpoint of the study was the proportion of patients who achieved SVR in the randomized treatment groups, and evaluated by a non-inferiority analysis. Based on this analysis, the study achieved its primary endpoint of non-inferiority with respect to SVR rates in the randomized 24 and 48-week telaprevir-based arms. The trial enrolled people at 76 clinical trial sites in the U.S. and Europe. A greater proportion of people in the ILLUMINATE study (approximately 90%) were enrolled at U.S. sites compared to the proportion in ADVANCE. As in all studies evaluating telaprevir-based regimens, patients received no more than 12 weeks of triple therapy (telaprevir, pegylated-interferon and ribavirin) followed by pegylated-interferon and ribavirin only, as part of either 24 or 48 weeks of total treatment, as noted in the trial design.
About the Telaprevir Development Program
To date, more than 2,500 people with hepatitis C have received telaprevir-based therapy as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE trials. Together, these studies enrolled people with genotype 1 hepatitis C who had not been treated for their disease previously as well as people who had been treated before but did not achieve a viral cure. The telaprevir clinical development program is the largest conducted to date for any investigational direct-acting antiviral hepatitis C therapy.
Phase 3 ADVANCE Trial
The pivotal Phase 3 ADVANCE study evaluated telaprevir-based response-guided regimens in 1,095 treatment-naïve patients. Data from this trial has been accepted for presentation at the 2010 Annual Meeting of the American Association for the Study of Liver Diseases.
Phase 3 REALIZE Trial
The second pivotal Phase 3 study, REALIZE, which is being conducted by Vertex's collaborator Tibotec, is evaluating telaprevir-based regimens in approximately 650 people who did not achieve a viral cure with a prior pegylated-interferon based treatment. REALIZE is the only current Phase 3 study of an investigational hepatitis C therapy to enroll a difficult-to-treat population that includes patients who had a null response and failed to achieve a viral cure with a prior course of hepatitis C therapy. Topline data from REALIZE are expected in September 2010.
Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
About Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the blood of people with the disease.2 According to a 2010 report from the Institute of Medicine, up to 3.9 million people in the United States have chronic hepatitis C and 75% of those infected are unaware of it.3 Approximately 60 percent of genotype 1 patients who undergo an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved treatment regimen, do not achieve a SVR 4,5,6 or viral cure.1
Hepatitis C is spread through direct contact with the blood of infected people.2 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.2 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure, or liver cancer.2 If treatment is not successful and a person does not achieve a viral cure, they remain at risk for progressive liver disease.7,8,9,10,11 In the United States, hepatitis C is the leading cause of liver transplantations and is reported to contribute to 4,600 to 12,000 deaths annually.8 The majority of people with hepatitis C were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.11 Over the next 20 years, total annual medical costs for people with hepatitis C are expected to more than double, from $30 billion today to approximately $85 billion.11
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer, and pain.
--Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
--Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
Additional resources for media, including a hepatitis C backgrounder and glossary of common terms, are available at: http://investors.vrtx.com/press.cfm
References:
1 Ghany, m.G., Strader, d.B., Thomas, d.L., Seeff, Leondard B. diagnosis, management and Treatment of Hepatitis C; An Update. 2009. Hepatology. 2009;49 (4):1-40.
2 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at:
http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed May 25, 2010.
3 Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Available at http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Accessed May 25, 2010.
4 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
5 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
6 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
7 Morgan T.R, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
8 Davis, G.L., Alter, M. J. , El-Serag, H. Clinical-Liver, Pancreas, and Biliary Tract. Journal of Gastroenterology. 2010;138: 513-521.
9 Volk, Michael I., Tocco, Rachel, Saini, Sameer, Lok, Anna S.F. Public Health Impact of Antiviral Therapy for Hepatitis C in the United States. Hepatology.2009;50(6):1750-1755.
10 Veldt, B.J., Heathcote, J., Wedmeyer, H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
11 Pyenson, B., Fitch, K., Iwasaki, K. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Milliman, Inc. This report was commissioned by Vertex Pharmaceuticals, Inc. May, 2009.
Special Note Regarding Forward-looking Statements
This press release contains forward-looking statements, including statements regarding (i) the potential importance of the ILLUMINATE results as described above by Drs. Sherman and Kauffman, (ii) data from ILLUMINATE supporting 24-week telaprevir-based therapy within a response-guided regimen, (iii) the expectation that results from ILLUMINATE will supplement data obtained from ADVANCE and REALIZE, (iv) the planed submission of a New Drug Application for telaprevir in the fourth quarter of 2010 and (v) the expectation that topline data from REALIZE will be available in September 2010. While the Company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that future outcomes from clinical trials of telaprevir (including the REALIZE clinical trial) may not be favorable or may be less favorable than the outcomes reported from ILLUMINATE, ADVANCE and earlier clinical trials of telaprevir; that the Company could experience unforeseen delays in submitting the NDA for telaprevir and/or obtaining approval to market telaprevir; that there may be varying interpretations of the data from the telaprevir clinical trials; and that future scientific, clinical, competitive or other market factors may adversely affect the potential for telaprevir-based combination therapy and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the Company's website at www.vrtx.com. The Company disclaims any obligation to update the information contained in this press release as new information becomes available.
Vertex Pharmaceuticals will host a conference call on Tuesday, August 10, 2010 at 8:30 a.m. ET to review recent developments. To listen to the call on the telephone, dial 888-466-4587 (U.S. and Canada) or 719-325-2180 (International) and the conference ID number is 6448142. Vertex is also providing a podcast MP3 file available for download on the Vertex website at http://www.vrtx.com/.
The call will be available for replay via telephone commencing August 10, 2010 at 12:00 p.m. ET running through 5:00 p.m. on August 24, 2010. The replay phone number for the U.S. and Canada is 888-203-1112. The international replay number is 719-457-0820 and the conference ID number is 6448142. Following the live webcast, an archived version will be available on Vertex's website until 5:00 p.m. on August 17, 2010.
(VRTX-GEN)
Photos/Multimedia Gallery Available: http://www.businesswire.com/cgi-bin/mmg.cgi?eid=6391442&lang=en
SOURCE: Vertex Pharmaceuticals Incorporated
Vertex Pharmaceuticals Incorporated
Media:
Amy Pasqua, 617-444-6992
or
Megan Pace, 617-444-6992
or
Investors:
Michael Partridge, 617-444-6108
or
Lora Pike, 617-444-6755
*Received in email update from Vertex*
August 9, 2010
Serum fibrosis markers are associated with liver disease progression in non-responder patients with chronic hepatitis C
Gut doi:10.1136/gut.2010.207423
Robert J Fontana 1, Jules L Dienstag 2, Herbert L Bonkovsky 3, Richard K Sterling 4, Deepa Naishadham 5, Zachary D Goodman 6, Anna S F Lok 1, Elizabeth C Wright 7, Grace L Su 1, the HALT-C Trial Group
+ Author Affiliations
1 Department of Internal Medicine, University of Michigan Medical School, Michigan, USA
2 Gastrointestinal Unit (Medical Services), Massachusetts General Hospital and the Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
3 Departments of Medicine and Molecular & Structural Biology and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Connecticut, USA
4 Hepatology Section, Virginia Commonwealth University Medical Center, Virginia, USA
5 New England Research Institutes, Massachusetts, USA
6 Armed Forces Institute of Pathology, Division of Hepatic Pathology and Veterans Administration Special Reference Laboratory for Pathology, Washington, USA
7 Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Maryland, USA
Correspondence to
Robert J Fontana, Department of Internal Medicine, University of Michigan, 3912 Taubman Center, Ann Arbor, Michigan, USA; rfontana@med.umich.edu
Revised 17 May 2010
Accepted 18 May 2010
Published Online First 30 July 2010
Abstract
Objectives The aim of this study was to explore the association of serum fibrosis marker levels with the risk of clinical and histological disease progression in a large cohort of patients with chronic hepatitis C (CHC).
Methods 462 prior non-responders to peginterferon and ribavirin enrolled in the randomised phase of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial had baseline and annual serum samples tested for hyaluronic acid (HA), N-terminal peptide of procollagen type 3, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and YKL-40. All patients underwent a pretreatment liver biopsy and follow-up biopsies at years 2 and 4. Histological progression was defined as a ≥2 point increase in Ishak fibrosis score in patients without cirrhosis. Clinical outcomes included development of decompensation, hepatocellular cancer, death or an increase in the CTP (Child–Turcotte–Pugh) score to ≥7.
Results Mean patient age was 49.5 years and 39% had histological cirrhosis at entry. Baseline HA, YKL-40 and TIMP-1 levels combined with other laboratory parameters were all significantly associated with clinical outcomes in the 69 (15%) patients with disease progression (p<0.0001). The best multivariate model to predict clinical outcomes included baseline bilirubin, albumin, international normalised ratio (INR) and YKL-40 levels. All of the baseline serum fibrosis marker levels were also significantly associated with histological fibrosis progression that developed in 70 (33%) of the 209 patients with cirrhosis (p <0.0001). However, baseline HA and platelet counts were best at predicting histological progression (area under the curve (AUC)=0.663).
Conclusion Pretreatment serum fibrosis marker levels are significantly increased in patients with CHC at risk of clinical and histological disease progression. If validated in additional cohorts, measurement of these markers could help identify patients with CHC who would benefit from more frequent and intensive monitoring.
Trial Registration Number NCT00006164.
Source
Robert J Fontana 1, Jules L Dienstag 2, Herbert L Bonkovsky 3, Richard K Sterling 4, Deepa Naishadham 5, Zachary D Goodman 6, Anna S F Lok 1, Elizabeth C Wright 7, Grace L Su 1, the HALT-C Trial Group
+ Author Affiliations
1 Department of Internal Medicine, University of Michigan Medical School, Michigan, USA
2 Gastrointestinal Unit (Medical Services), Massachusetts General Hospital and the Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
3 Departments of Medicine and Molecular & Structural Biology and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Connecticut, USA
4 Hepatology Section, Virginia Commonwealth University Medical Center, Virginia, USA
5 New England Research Institutes, Massachusetts, USA
6 Armed Forces Institute of Pathology, Division of Hepatic Pathology and Veterans Administration Special Reference Laboratory for Pathology, Washington, USA
7 Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Maryland, USA
Correspondence to
Robert J Fontana, Department of Internal Medicine, University of Michigan, 3912 Taubman Center, Ann Arbor, Michigan, USA; rfontana@med.umich.edu
Revised 17 May 2010
Accepted 18 May 2010
Published Online First 30 July 2010
Abstract
Objectives The aim of this study was to explore the association of serum fibrosis marker levels with the risk of clinical and histological disease progression in a large cohort of patients with chronic hepatitis C (CHC).
Methods 462 prior non-responders to peginterferon and ribavirin enrolled in the randomised phase of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial had baseline and annual serum samples tested for hyaluronic acid (HA), N-terminal peptide of procollagen type 3, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and YKL-40. All patients underwent a pretreatment liver biopsy and follow-up biopsies at years 2 and 4. Histological progression was defined as a ≥2 point increase in Ishak fibrosis score in patients without cirrhosis. Clinical outcomes included development of decompensation, hepatocellular cancer, death or an increase in the CTP (Child–Turcotte–Pugh) score to ≥7.
Results Mean patient age was 49.5 years and 39% had histological cirrhosis at entry. Baseline HA, YKL-40 and TIMP-1 levels combined with other laboratory parameters were all significantly associated with clinical outcomes in the 69 (15%) patients with disease progression (p<0.0001). The best multivariate model to predict clinical outcomes included baseline bilirubin, albumin, international normalised ratio (INR) and YKL-40 levels. All of the baseline serum fibrosis marker levels were also significantly associated with histological fibrosis progression that developed in 70 (33%) of the 209 patients with cirrhosis (p <0.0001). However, baseline HA and platelet counts were best at predicting histological progression (area under the curve (AUC)=0.663).
Conclusion Pretreatment serum fibrosis marker levels are significantly increased in patients with CHC at risk of clinical and histological disease progression. If validated in additional cohorts, measurement of these markers could help identify patients with CHC who would benefit from more frequent and intensive monitoring.
Trial Registration Number NCT00006164.
Source
Activation of brain macrophages/microglia cells in hepatitis C infection
Gut doi:10.1136/gut.2009.199356
Jeffrey Wilkinson 1, Marek Radkowski 2, Jennifer M Eschbacher 1, Tomasz Laskus 1,2
+ Author Affiliations
1 Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA
2 Institute of Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
Correspondence to
Tomasz Laskus, Medical University of Warsaw, Pawinskiego 7C 02-106 Warsaw, Poland; immunopa@amwaw.edu.pl
Revised 23 April 2010
Accepted 27 April 2010
Published Online First 30 July 2010
Abstract
Objectives Hepatitis C virus (HCV) infection is commonly associated with cognitive dysfunction. Viral sequences and proteins were previously found in brain macrophage/microglia cells. The aim of the current study was to determine whether HCV infection affects the expression of key cytokines and chemokines in these cells.
Methods Autopsy brain tissue from 15 patients was studied; 7 patients were HCV positive and 8 were HCV negative. Cryostat sections of frontal cortex and subcortical white matter were stained with monoclonal antibodies specific for microglia/macrophages (anti-CD68) and separated by laser capture microscopy. Transcripts representing 25 various cytokines and chemokines were measured by real-time quantitative PCR.
Results Compared with HCV-negative controls, HCV-positive patients demonstrated significantly higher levels of proinflammatory cytokines interleukin 1α (IL-1α), IL-1β, tumour necrosis factor α (TNFα), IL-12 and IL-18. HCV infection was also associated with increased transcription of chemokines IL-8, IL-16 and interferon-inducible protein 10 (IP-10). Type 1 interferon (IFN) activation was suggested by increased concentrations of IFNβ and myxovirus resistance protein A (MxA) transcripts. Similar results were obtained when CD68-positive/HCV-positive cells were compared with CD68-positive/HCV-negative cells in each of the 7 HCV-infected patients.
Conclusion Evidence was found for activation of brain macrophages/microglia cells in autopsy brain tissue from HCV-positive patients. These findings could relate to the common presence of neurocognitive dysfunction among patients with chronic hepatitis C.
Source
Jeffrey Wilkinson 1, Marek Radkowski 2, Jennifer M Eschbacher 1, Tomasz Laskus 1,2
+ Author Affiliations
1 Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA
2 Institute of Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
Correspondence to
Tomasz Laskus, Medical University of Warsaw, Pawinskiego 7C 02-106 Warsaw, Poland; immunopa@amwaw.edu.pl
Revised 23 April 2010
Accepted 27 April 2010
Published Online First 30 July 2010
Abstract
Objectives Hepatitis C virus (HCV) infection is commonly associated with cognitive dysfunction. Viral sequences and proteins were previously found in brain macrophage/microglia cells. The aim of the current study was to determine whether HCV infection affects the expression of key cytokines and chemokines in these cells.
Methods Autopsy brain tissue from 15 patients was studied; 7 patients were HCV positive and 8 were HCV negative. Cryostat sections of frontal cortex and subcortical white matter were stained with monoclonal antibodies specific for microglia/macrophages (anti-CD68) and separated by laser capture microscopy. Transcripts representing 25 various cytokines and chemokines were measured by real-time quantitative PCR.
Results Compared with HCV-negative controls, HCV-positive patients demonstrated significantly higher levels of proinflammatory cytokines interleukin 1α (IL-1α), IL-1β, tumour necrosis factor α (TNFα), IL-12 and IL-18. HCV infection was also associated with increased transcription of chemokines IL-8, IL-16 and interferon-inducible protein 10 (IP-10). Type 1 interferon (IFN) activation was suggested by increased concentrations of IFNβ and myxovirus resistance protein A (MxA) transcripts. Similar results were obtained when CD68-positive/HCV-positive cells were compared with CD68-positive/HCV-negative cells in each of the 7 HCV-infected patients.
Conclusion Evidence was found for activation of brain macrophages/microglia cells in autopsy brain tissue from HCV-positive patients. These findings could relate to the common presence of neurocognitive dysfunction among patients with chronic hepatitis C.
Source
The Rules...The dos and don'ts when someone you know is diagnosed.
BY LESLIE STARSONECK
The dos and don'ts when someone you know is diagnosed.
People want to know the rules about what to do or say when a friend or family member is diagnosed with cancer. Here are my experiences and suggestions.
> “My aunt had cancer”: When I was first diagnosed and sharing the news with friends and family, I didn’t want to hear about other people who had cancer. It made me feel like I needed to be empathetic to that person—who was usually a stranger—or sympathetic to the person telling me, at a time when I had trouble mustering much energy beyond saying what was happening to me. I also quickly learned that these disclosures rarely had any value to me medically because of how very different each person is in terms of the stage, biology, and treatment for the disease.
> Ask: Ask whether the person facing cancer is comfortable sharing the details of their prognosis and treatment. If the patient tells you, it may give you an idea of how you can help. On the other hand, if you ask and get only vague details, you should accept this as a request for privacy and not ask others to provide this information.
> Respond: Even if you’re at a loss for words, say something when a person tells you about his or her diagnosis. Say that you’re at a loss for words or don’t know what to say, but don’t remain silent or ignore the elephant in the room by talking about everything else. This says to the patient, “You shouldn’t have told me this because I can’t handle it.”
> Help: Ask the patient if they want your help, and be specific about how you can help. This goes for little things, such as doing the laundry, and big things, such as publicly honoring them at a race or fundraiser.
> Don’t forget the caregiver: Whether it’s helping with some of the caregiver’s responsibilities (for example, running errands), delivering leisure items for them to use during “downtime,” or getting them out of the house, make sure to ask permission to help in specific ways. Then make sure to follow through.
> It’s OK to say or do the wrong thing: Remember that what you do or say to the patient doesn’t have to be perfect. The most important thing is that it’s genuine and based on care and concern. It’s so much better to say or do the wrong thing than to not say or do anything at all.
> It doesn’t end with recovery from surgery: Having the many phases of the journey acknowledged by others was important for me—fear of recurrence, the inevitable adjustments to medication, or the new way my body looks and feels—as opposed to treating cancer as a series of discrete events.
> Keep in touch: Show the patient that you recognize that cancer—whatever its particular path—is a journey.
> Set realistic expectations: This rule is for patients who, like me, may have learned that family and friends don’t suddenly change their personalities because you have cancer. There may be instances where people step up who you thought wouldn’t, or people you thought you could rely on who you can’t. But for the most part, how someone responds will be in keeping with how he or she has always been.
—Breast cancer survivor Leslie Starsoneck lives in Raleigh, North Carolina.
Source
The dos and don'ts when someone you know is diagnosed.
People want to know the rules about what to do or say when a friend or family member is diagnosed with cancer. Here are my experiences and suggestions.
> “My aunt had cancer”: When I was first diagnosed and sharing the news with friends and family, I didn’t want to hear about other people who had cancer. It made me feel like I needed to be empathetic to that person—who was usually a stranger—or sympathetic to the person telling me, at a time when I had trouble mustering much energy beyond saying what was happening to me. I also quickly learned that these disclosures rarely had any value to me medically because of how very different each person is in terms of the stage, biology, and treatment for the disease.
> Ask: Ask whether the person facing cancer is comfortable sharing the details of their prognosis and treatment. If the patient tells you, it may give you an idea of how you can help. On the other hand, if you ask and get only vague details, you should accept this as a request for privacy and not ask others to provide this information.
> Respond: Even if you’re at a loss for words, say something when a person tells you about his or her diagnosis. Say that you’re at a loss for words or don’t know what to say, but don’t remain silent or ignore the elephant in the room by talking about everything else. This says to the patient, “You shouldn’t have told me this because I can’t handle it.”
> Help: Ask the patient if they want your help, and be specific about how you can help. This goes for little things, such as doing the laundry, and big things, such as publicly honoring them at a race or fundraiser.
> Don’t forget the caregiver: Whether it’s helping with some of the caregiver’s responsibilities (for example, running errands), delivering leisure items for them to use during “downtime,” or getting them out of the house, make sure to ask permission to help in specific ways. Then make sure to follow through.
> It’s OK to say or do the wrong thing: Remember that what you do or say to the patient doesn’t have to be perfect. The most important thing is that it’s genuine and based on care and concern. It’s so much better to say or do the wrong thing than to not say or do anything at all.
> It doesn’t end with recovery from surgery: Having the many phases of the journey acknowledged by others was important for me—fear of recurrence, the inevitable adjustments to medication, or the new way my body looks and feels—as opposed to treating cancer as a series of discrete events.
> Keep in touch: Show the patient that you recognize that cancer—whatever its particular path—is a journey.
> Set realistic expectations: This rule is for patients who, like me, may have learned that family and friends don’t suddenly change their personalities because you have cancer. There may be instances where people step up who you thought wouldn’t, or people you thought you could rely on who you can’t. But for the most part, how someone responds will be in keeping with how he or she has always been.
—Breast cancer survivor Leslie Starsoneck lives in Raleigh, North Carolina.
Source
Projecting Possible Future Courses of the HIV Epidemic in the United States
August 2010
The Future of HIV
The U.S. HIV epidemic has claimed more than 575,000 lives, and 56,300 Americans were newly infected with HIV in 2006. HIV prevention efforts to date have helped hundreds of thousands of people avoid infection, but have not reached enough of those currently at risk of acquiring or transmitting HIV with highly effective interventions to turn the course of the epidemic.
To help set U.S. HIV prevention goals, determine prevention program needs, and project future healthcare costs, the Centers for Disease Control and Prevention and Johns Hopkins University conducted an analysis [1] that projects what the HIV epidemic in the United States might look like in 10 years under different scenarios.
The CDC/Johns Hopkins study reveals that maintaining status quo HIV prevention efforts could put the nation on a dangerous trajectory, resulting in substantial increases in HIV and related costs to the U.S. healthcare system.
Unprecedented Challenges in HIV Prevention
Nearly 30 years into the HIV epidemic, HIV continues to take a heavy toll in the United States. More than 1.1 million people are currently living with HIV, nearly 18,000 people with AIDS still die each year, and lifetime medical care for those who become infected with HIV each year is estimated to cost $20 billion. Gay and bisexual men of all races, African-Americans, Latinos, and injection drug users are most affected.
In the fight against HIV, the nation is facing unprecedented challenges:
The CDC/Johns Hopkins study examined five scenarios: three scenarios examined likely outcomes of status quo HIV prevention efforts (“base-case scenarios”), and two scenarios investigated the impact of a significant expansion of HIV prevention efforts (“intensified intervention scenarios”).
As indicated in the graphs on the following page, the study found that rapid scale up of HIV prevention efforts could substantially reduce the number of HIV infections and the number of people living with HIV over the next 10 years, compared to the base-case scenarios.
Status Quo in HIV Prevention Could Translate into a Worsening U.S. HIV Epidemic
Researchers examined three “base-case scenarios” that assumed different epidemiologic trends and a continuation of current federal HIV prevention funding levels. Each scenario estimated the impact on future HIV incidence and prevalence (see box on this page for definitions) over the next 10 years. The study found that continuing current trends could increase the number of people living with HIV by as much as 38 percent, and would cost the U.S. healthcare system an additional $128 billion to $237 billion in medical care costs for those who become infected.
Stable HIV incidence: One scenario assumed that the number of annual new HIV infections would remain constant over the next 10 years at 55,400, which the study projected would increase national HIV prevalence by 29 percent (from 1.107 million to 1.427 million people living with HIV). This scenario is plausible given continued high HIV incidence among men who have sex with men — who make up the majority of individuals infected with HIV — and declining incidence among other risk groups. To hold HIV incidence stable in the face of increasing prevalence means that the HIV transmission rate would have to substantially decline.
Definitions
HIV prevalence: The number of people living with HIV — with or without a diagnosis of AIDS — at a point in time. CDC estimates that there were more than 1.1 million people living with HIV in the United States at the end of 2006.
HIV incidence: The number of people who become newly infected with HIV each year. CDC estimates that there were 56,300 new HIV infections in 2006. (The analysis described here draws on historical trends that indicate that 55,400 annual new infections occurred in the United States each year between 2003 and 2006.)
HIV transmission rate: Indicates the estimated number of new HIV infections transmitted per year per person living with HIV. CDC estimates that there were 5 transmissions for every 100 individuals living with HIV in the United States in 2006.
Continued decline in national HIV transmission rate: The most optimistic base-case scenario assumed a continuation of the downward trend in the nation’s HIV transmission rate observed in recent years (2000–2006), such that the HIV transmission rate would decline in 10 years from 5.0 to 3.1 new HIV infections per 100 persons living with HIV. Under this scenario, the study projected that HIV prevalence would increase by 24 percent (from 1.107 million to 1.373 million people living with HIV) and that HIV incidence would decline by 24 percent (from 55,400 to 42,300 annual new HIV infections). For this scenario to be realized, it would be necessary to discover and achieve enough new efficiencies in HIV prevention efforts to offset substantial cuts to HIV prevention budgets at state and local levels.
Stable HIV transmission rate: The most pessimistic base-case scenario projected the impact of a static HIV transmission rate (at the current CDC estimate of 5.0 new HIV infections transmitted annually per 100 persons living with HIV). It found that both HIV prevalence and incidence would increase by 38 percent (from 1.107 million to 1.530 million people living with HIV, and from 55,400 to 76,600 annual new HIV infections). Recent cuts to state and local HIV prevention budgets may make it difficult to make further progress in reducing HIV transmission.
Rapid Scale Up of HIV Prevention Efforts Could Save the Most Lives and Money
The study found that a rapid expansion of HIV prevention efforts could most effectively reduce the number of new HIV infections in the United States, and save the U.S. healthcare system up to 25 times the amount that would need to be invested in prevention.
Based on expert recommendations provided to Congress in 2008 [5,6], the researchers examined two “intensified intervention scenarios” that assumed a significant increase in the federal investment in HIV prevention in order to achieve a 50 percent reduction in the national HIV transmission rate (from 5.0 to 2.5 new infections per 100 persons living with HIV). One scenario examined the prevention interventions and resources that would be needed to cut the HIV transmission rate in half in five years; the other scenario investigated the interventions and resources that would be needed to cut the transmission rate in half in 10 years. Both scenarios placed considerable emphasis on expanding access to HIV testing and behavioral interventions for people living with HIV and those at very high risk of contracting HIV, though they made different assumptions about other HIV prevention efforts that would be required (e.g., local capacity building, HIV surveillance, research, and evaluation).
The study found that the greatest gains could be achieved by scaling up prevention in five years:
The release of the National HIV/AIDS Strategy in July, 2010 gives the HIV prevention community an opportunity to redefine our nation’s approach to HIV prevention and calls for shared responsibility to end the U.S. epidemic. Modeling studies, such as this one, can help guide appropriate actions as we collectively move forward to implement the National HIV/AIDS Strategy. It is clear that progress will require us to direct available resources to the populations and geographic areas with the most urgent needs. Additionally, we must expand HIV prevention efforts for individuals at the highest risk of HIV transmission and infection; ensure a focus on community-level interventions that address underlying HIV risk factors in hardest-hit areas; and work to ensure basic, fundamental HIV knowledge among all Americans.
References
Last Reviewed: August 9, 2010
Content Source:
Divisions of HIV/AIDS Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Source
The Future of HIV
The U.S. HIV epidemic has claimed more than 575,000 lives, and 56,300 Americans were newly infected with HIV in 2006. HIV prevention efforts to date have helped hundreds of thousands of people avoid infection, but have not reached enough of those currently at risk of acquiring or transmitting HIV with highly effective interventions to turn the course of the epidemic.
To help set U.S. HIV prevention goals, determine prevention program needs, and project future healthcare costs, the Centers for Disease Control and Prevention and Johns Hopkins University conducted an analysis [1] that projects what the HIV epidemic in the United States might look like in 10 years under different scenarios.
The CDC/Johns Hopkins study reveals that maintaining status quo HIV prevention efforts could put the nation on a dangerous trajectory, resulting in substantial increases in HIV and related costs to the U.S. healthcare system.
Unprecedented Challenges in HIV Prevention
Nearly 30 years into the HIV epidemic, HIV continues to take a heavy toll in the United States. More than 1.1 million people are currently living with HIV, nearly 18,000 people with AIDS still die each year, and lifetime medical care for those who become infected with HIV each year is estimated to cost $20 billion. Gay and bisexual men of all races, African-Americans, Latinos, and injection drug users are most affected.
In the fight against HIV, the nation is facing unprecedented challenges:
- Impact of economic crisis: The current economic crisis has severely impacted state and local governments and community-based organizations, with $170 million in cuts to state HIV/AIDS prevention and care programs in fiscal year 2009 alone [2]. These cuts mean that essential HIV prevention services will reach fewer of those at risk of HIV infection. In addition, waiting lists for the federal AIDS Drug Assistance Program (ADAP), which provides HIV treatment to low-income individuals, are at record highs.
- Increasing HIV prevalence: It is anticipated that the number of people living with HIV will continue to increase over time, due to the remarkable benefits of life-prolonging HIV treatments. As more people live with HIV, opportunities for transmission increase, as does the need for prevention services and medical care.
- Complacency: Despite the severe impact of HIV in the United States, studies show that many Americans — even those at greatest risk of infection — have grown complacent about HIV [3,4]. This is a major concern since lack of awareness about HIV can contribute to increased risk behaviors, and reduce community and governmental mobilization.
The CDC/Johns Hopkins study examined five scenarios: three scenarios examined likely outcomes of status quo HIV prevention efforts (“base-case scenarios”), and two scenarios investigated the impact of a significant expansion of HIV prevention efforts (“intensified intervention scenarios”).
As indicated in the graphs on the following page, the study found that rapid scale up of HIV prevention efforts could substantially reduce the number of HIV infections and the number of people living with HIV over the next 10 years, compared to the base-case scenarios.
Status Quo in HIV Prevention Could Translate into a Worsening U.S. HIV Epidemic
Researchers examined three “base-case scenarios” that assumed different epidemiologic trends and a continuation of current federal HIV prevention funding levels. Each scenario estimated the impact on future HIV incidence and prevalence (see box on this page for definitions) over the next 10 years. The study found that continuing current trends could increase the number of people living with HIV by as much as 38 percent, and would cost the U.S. healthcare system an additional $128 billion to $237 billion in medical care costs for those who become infected.
Stable HIV incidence: One scenario assumed that the number of annual new HIV infections would remain constant over the next 10 years at 55,400, which the study projected would increase national HIV prevalence by 29 percent (from 1.107 million to 1.427 million people living with HIV). This scenario is plausible given continued high HIV incidence among men who have sex with men — who make up the majority of individuals infected with HIV — and declining incidence among other risk groups. To hold HIV incidence stable in the face of increasing prevalence means that the HIV transmission rate would have to substantially decline.
Definitions
HIV prevalence: The number of people living with HIV — with or without a diagnosis of AIDS — at a point in time. CDC estimates that there were more than 1.1 million people living with HIV in the United States at the end of 2006.
HIV incidence: The number of people who become newly infected with HIV each year. CDC estimates that there were 56,300 new HIV infections in 2006. (The analysis described here draws on historical trends that indicate that 55,400 annual new infections occurred in the United States each year between 2003 and 2006.)
HIV transmission rate: Indicates the estimated number of new HIV infections transmitted per year per person living with HIV. CDC estimates that there were 5 transmissions for every 100 individuals living with HIV in the United States in 2006.
Continued decline in national HIV transmission rate: The most optimistic base-case scenario assumed a continuation of the downward trend in the nation’s HIV transmission rate observed in recent years (2000–2006), such that the HIV transmission rate would decline in 10 years from 5.0 to 3.1 new HIV infections per 100 persons living with HIV. Under this scenario, the study projected that HIV prevalence would increase by 24 percent (from 1.107 million to 1.373 million people living with HIV) and that HIV incidence would decline by 24 percent (from 55,400 to 42,300 annual new HIV infections). For this scenario to be realized, it would be necessary to discover and achieve enough new efficiencies in HIV prevention efforts to offset substantial cuts to HIV prevention budgets at state and local levels.
Stable HIV transmission rate: The most pessimistic base-case scenario projected the impact of a static HIV transmission rate (at the current CDC estimate of 5.0 new HIV infections transmitted annually per 100 persons living with HIV). It found that both HIV prevalence and incidence would increase by 38 percent (from 1.107 million to 1.530 million people living with HIV, and from 55,400 to 76,600 annual new HIV infections). Recent cuts to state and local HIV prevention budgets may make it difficult to make further progress in reducing HIV transmission.
Rapid Scale Up of HIV Prevention Efforts Could Save the Most Lives and Money
The study found that a rapid expansion of HIV prevention efforts could most effectively reduce the number of new HIV infections in the United States, and save the U.S. healthcare system up to 25 times the amount that would need to be invested in prevention.
Based on expert recommendations provided to Congress in 2008 [5,6], the researchers examined two “intensified intervention scenarios” that assumed a significant increase in the federal investment in HIV prevention in order to achieve a 50 percent reduction in the national HIV transmission rate (from 5.0 to 2.5 new infections per 100 persons living with HIV). One scenario examined the prevention interventions and resources that would be needed to cut the HIV transmission rate in half in five years; the other scenario investigated the interventions and resources that would be needed to cut the transmission rate in half in 10 years. Both scenarios placed considerable emphasis on expanding access to HIV testing and behavioral interventions for people living with HIV and those at very high risk of contracting HIV, though they made different assumptions about other HIV prevention efforts that would be required (e.g., local capacity building, HIV surveillance, research, and evaluation).
The study found that the greatest gains could be achieved by scaling up prevention in five years:
- Expanding HIV prevention in 5 years: The study found that intensifying national HIV prevention efforts over a five-year timeframe and maintaining them for the subsequent five years could reduce annual HIV incidence by 46 percent (from 55,400 to 30,200 new infections) — saving as many as an additional 306,000 people from becoming infected over the next 10 years — compared to maintaining current prevention efforts. HIV prevalence in this scenario would increase by only 13 percent (from 1.107 million to 1.247 million people living with HIV) — the smallest increase of any scenario included in the analysis. This rapid scale up would also save 25 times the amount that would need to be invested: expanding HIV prevention in five years would require an additional investment of $4.5 billion over 10 years, and would save up to $104 billion in avoided lifetime medical costs.
- Expanding HIV prevention in 10 years: The study shows that expanding HIV prevention over a 10-year timeframe could reduce national HIV incidence by 40 percent (from 55,400 to 33,300 new infections) — preventing as many as an additional 215,000 new infections. In this scenario, HIV prevalence would increase by 20 percent (from 1.107 million to 1.329 million people living with HIV) — lower than any of the “base-case scenarios.” This expansion of HIV prevention would require an additional investment of $10.1 billion over 10 years, and would save as much as $66 billion in averted lifetime medical costs.
The release of the National HIV/AIDS Strategy in July, 2010 gives the HIV prevention community an opportunity to redefine our nation’s approach to HIV prevention and calls for shared responsibility to end the U.S. epidemic. Modeling studies, such as this one, can help guide appropriate actions as we collectively move forward to implement the National HIV/AIDS Strategy. It is clear that progress will require us to direct available resources to the populations and geographic areas with the most urgent needs. Additionally, we must expand HIV prevention efforts for individuals at the highest risk of HIV transmission and infection; ensure a focus on community-level interventions that address underlying HIV risk factors in hardest-hit areas; and work to ensure basic, fundamental HIV knowledge among all Americans.
References
- Hall HI, Green TA, Wolitski RJ, et al. Estimated future HIV prevalence, incidence, and potential infections averted in the United States: a multiple scenario analysis. J Acquir Immune Defic Syndr 2010 July 30; volume published ahead of print.
- National Alliance of State and Territorial AIDS Directors. Support FY2011 HIV prevention funding.
- Kaiser Family Foundation. 2009 survey of Americans on HIV/AIDS: summary of findings on the domestic epidemic. April 2009.
- MacKellar DA, Valleroy LA, Secura GM, et al. Perceptions of lifetime risk and actual risk for acquiring HIV among young men who have sex with men. AIDS Behav 2007 Mar; 11 (2) 263-270.
- Holtgrave DR. Written testimony on HIV/AIDS incidence and prevention for the U.S. House of Representatives Committee on Oversight and Government Reform. September 16, 2008.
- CDC. HIV/AIDS in the United States: a look back and a look forward. Statement of Julie L. Gerberding before the U.S. House of Representatives Committee on Oversight and Government Reform. September 16, 2008.
Last Reviewed: August 9, 2010
Content Source:
Divisions of HIV/AIDS Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Source
Learn More About Stem Cell Research and Treatment
Monday August 9, 2010
This is a great initiative. The International Society for Stem Cell Research has recently started a a the ISSCR Task Force on Unproven Stem Cell Treatments to investigate individual clinics that claim to be providing stem cell treatments and cures. Called "A Closer Look at Stem Cell Treatments," their website gives people the opportunity to submit the name of clinics for review. From what I understand, the Society is not going to look at patient outcome data, but really wants to make sure that patients' rights are protected and that the clinics are being supervised by regulatory bodies in their countries or regions.
Before anyone jumps to the conclusion that this organization is comprised of a bunch of nay-sayers or people who are against embryonic stem cell research and trying to shut down such efforts, let me reassure you that this group is interested in the integrity of stem cell science and medicine because they believe in it. These are people working in the field who want to keep stem cell science clean and free of scandal and charlatans. As their website states:
"The International Society for Stem Cell Research (ISSCR; http://www.isscr.org/) is an independent, nonprofit organization established to promote and foster the exchange and dissemination of information and ideas relating to stem cells, to encourage the general field of research involving stem cells and to promote professional and public education in all areas of stem cell research and application. Members are admitted on the basis of their professional credentials as scientists or clinicians working in the field of stem cell research."
The website also offers great resources for anyone interested in stem cell approaches, such as The Patient Handbook on Stem Cell Therapies and articles explaining the current state of stem cell research and treatment.
Source
This is a great initiative. The International Society for Stem Cell Research has recently started a a the ISSCR Task Force on Unproven Stem Cell Treatments to investigate individual clinics that claim to be providing stem cell treatments and cures. Called "A Closer Look at Stem Cell Treatments," their website gives people the opportunity to submit the name of clinics for review. From what I understand, the Society is not going to look at patient outcome data, but really wants to make sure that patients' rights are protected and that the clinics are being supervised by regulatory bodies in their countries or regions.
Before anyone jumps to the conclusion that this organization is comprised of a bunch of nay-sayers or people who are against embryonic stem cell research and trying to shut down such efforts, let me reassure you that this group is interested in the integrity of stem cell science and medicine because they believe in it. These are people working in the field who want to keep stem cell science clean and free of scandal and charlatans. As their website states:
"The International Society for Stem Cell Research (ISSCR; http://www.isscr.org/) is an independent, nonprofit organization established to promote and foster the exchange and dissemination of information and ideas relating to stem cells, to encourage the general field of research involving stem cells and to promote professional and public education in all areas of stem cell research and application. Members are admitted on the basis of their professional credentials as scientists or clinicians working in the field of stem cell research."
The website also offers great resources for anyone interested in stem cell approaches, such as The Patient Handbook on Stem Cell Therapies and articles explaining the current state of stem cell research and treatment.
Source
New antiviral drug shows promise for dramatic improvement in hepatitis C treatment
Public release date: 8-Aug-2010
Contact: Eric Schoch
eschoch@iupui.edu
317-274-7722
Indiana University School of Medicine
INDIANAPOLIS — Adding a direct acting anti-viral drug to the standard treatment regimen for hepatitis C significantly increases the cure rate in the most difficult to treat patients, according to a research report published Monday in the online edition of the journal The Lancet.
The research team, led by Paul Kwo, M.D., of Indiana University School of Medicine, reported that adding the drug nearly doubled the treatment's effectiveness when given for 48 weeks in one treatment arm of the study.
An estimated 3.2 million Americans and 170 million people worldwide are infected with the hepatitis C virus, but many do not know it. In the United States, 70 percent of affected individuals are infected with genotype 1 hepatitis C, the most difficult to treat. Although there may be no symptoms for years, long-term infection can cause cirrhosis and the disease is a leading cause of liver cancer and liver transplantation. Hepatitis C infections occur mainly through transmission of infected blood, such as via injection drug use, and there is no vaccine.
Currently fewer than half of patients with genotype 1 hepatitis C are treated effectively by the standard combination of two drugs, peginterferon alfa-2b plus ribavirin, which is typically given for 48 weeks. The treatment can be difficult for some patients due to anemia and other side effects.
Adding the drug boceprevir increased the cure rate to as high as 75 percent in those who received 48 weeks of the three-drug combination therapy, compared to 38 percent of those in the control group, who received the standard two-drug treatment for 48 weeks, said Dr. Kwo, associate professor of medicine at the IU School of Medicine. The two-year phase 2 trial was conducted at 67 sites with 520 patients in the U.S., Canada and Europe.
In the boceprevir study, known as the SPRINT-1 trial, researchers tested several different options to evaluate the effectiveness of the combination therapy:
•To test whether the addition of boceprevir could make it possible to shorten treatment times, some patients were randomly selected to receive the three-drug combination for 28 weeks, some for 48 weeks.
•Researchers also investigated whether a 4 week lead-in with the standard two-drug combination prior to the addition of boceprevir to the treatment regime could improve sustained virologic response rates. The goal was to see if allowing the interferon and ribavirin to reach steady state levels -- which would activate the immune system and reduce virus levels -- before adding boceprevir would improve the response rates as well as reduce the virus' ability to develop resistance to boceprevir, said Kwo.
•In another arm of the trial, researchers tested whether a lower dose of ribavirin could reduce the anemia side effects while still treating the virus effectively.
"Both 28- and 48-week boceprevir regimens significantly increased sustained virologic response rates – which is the best definition of a cure we have – compared to the 48 week control," said Dr. Kwo. "The 48-week treatment arm with 4 weeks of peg interferon lead-in and 44 weeks of peg interferon, ribavirin, and boceprevir led to the largest improvement over the control group ever reported. That's very impressive."
Boceprevir, a product of Merck & Co., is an HCV protease inhibitor – a compound designed to block a function key to viral reproduction in the cell. Boceprevir directly targets the hepatitis C virus, Kwo noted, while peginterferon and ribavirin are less specific, acting more generally to stimulate the body's virus-fighting immune system.
The best results were reported for the 103 patients who were treated for four weeks with the standard two drug regiment, followed by 44 weeks of the three-drug regimen including boceprevir: 75 percent of these patients tested negative for evidence of the virus six months after the end of treatment. Results for the other treatment arms were:
•67 percent of those who received the three drug regimen for 48 weeks with no lead-in treatment tested negative for the virus (103 patients).
•56 percent of those who received the two-drug lead-in for four weeks, followed by 24 weeks of the three drug treatment tested negative for the virus (103 patients).
•54 percent of those who received the three-drug treatment for 28 weeks with no lead-in tested negative for the virus (107 patients).
•38 percent of the control group, who received the standard two-drug treatment for 48 weeks tested negative for the virus (104 patients).
Patients receiving the low-dose of ribavirin did not fare as well – just 36 percent were virus-free after 48 weeks of treatment.
"Based on this phase 2 study, it appears that if this drug receives final approval approximately two-thirds of patients will be able to be treated successfully with 28 weeks of treatment and one-third will need 48 weeks of treatment, though this will require confirmation from the phase 3 trials, from which preliminary results were recently released," said Dr. Kwo.
###
The research was funded by Schering Corp. a division of Merck & Co., which provided assistance with the trial, data collection and analysis, and the manuscript.
Source
Contact: Eric Schoch
eschoch@iupui.edu
317-274-7722
Indiana University School of Medicine
INDIANAPOLIS — Adding a direct acting anti-viral drug to the standard treatment regimen for hepatitis C significantly increases the cure rate in the most difficult to treat patients, according to a research report published Monday in the online edition of the journal The Lancet.
The research team, led by Paul Kwo, M.D., of Indiana University School of Medicine, reported that adding the drug nearly doubled the treatment's effectiveness when given for 48 weeks in one treatment arm of the study.
An estimated 3.2 million Americans and 170 million people worldwide are infected with the hepatitis C virus, but many do not know it. In the United States, 70 percent of affected individuals are infected with genotype 1 hepatitis C, the most difficult to treat. Although there may be no symptoms for years, long-term infection can cause cirrhosis and the disease is a leading cause of liver cancer and liver transplantation. Hepatitis C infections occur mainly through transmission of infected blood, such as via injection drug use, and there is no vaccine.
Currently fewer than half of patients with genotype 1 hepatitis C are treated effectively by the standard combination of two drugs, peginterferon alfa-2b plus ribavirin, which is typically given for 48 weeks. The treatment can be difficult for some patients due to anemia and other side effects.
Adding the drug boceprevir increased the cure rate to as high as 75 percent in those who received 48 weeks of the three-drug combination therapy, compared to 38 percent of those in the control group, who received the standard two-drug treatment for 48 weeks, said Dr. Kwo, associate professor of medicine at the IU School of Medicine. The two-year phase 2 trial was conducted at 67 sites with 520 patients in the U.S., Canada and Europe.
In the boceprevir study, known as the SPRINT-1 trial, researchers tested several different options to evaluate the effectiveness of the combination therapy:
•To test whether the addition of boceprevir could make it possible to shorten treatment times, some patients were randomly selected to receive the three-drug combination for 28 weeks, some for 48 weeks.
•Researchers also investigated whether a 4 week lead-in with the standard two-drug combination prior to the addition of boceprevir to the treatment regime could improve sustained virologic response rates. The goal was to see if allowing the interferon and ribavirin to reach steady state levels -- which would activate the immune system and reduce virus levels -- before adding boceprevir would improve the response rates as well as reduce the virus' ability to develop resistance to boceprevir, said Kwo.
•In another arm of the trial, researchers tested whether a lower dose of ribavirin could reduce the anemia side effects while still treating the virus effectively.
"Both 28- and 48-week boceprevir regimens significantly increased sustained virologic response rates – which is the best definition of a cure we have – compared to the 48 week control," said Dr. Kwo. "The 48-week treatment arm with 4 weeks of peg interferon lead-in and 44 weeks of peg interferon, ribavirin, and boceprevir led to the largest improvement over the control group ever reported. That's very impressive."
Boceprevir, a product of Merck & Co., is an HCV protease inhibitor – a compound designed to block a function key to viral reproduction in the cell. Boceprevir directly targets the hepatitis C virus, Kwo noted, while peginterferon and ribavirin are less specific, acting more generally to stimulate the body's virus-fighting immune system.
The best results were reported for the 103 patients who were treated for four weeks with the standard two drug regiment, followed by 44 weeks of the three-drug regimen including boceprevir: 75 percent of these patients tested negative for evidence of the virus six months after the end of treatment. Results for the other treatment arms were:
•67 percent of those who received the three drug regimen for 48 weeks with no lead-in treatment tested negative for the virus (103 patients).
•56 percent of those who received the two-drug lead-in for four weeks, followed by 24 weeks of the three drug treatment tested negative for the virus (103 patients).
•54 percent of those who received the three-drug treatment for 28 weeks with no lead-in tested negative for the virus (107 patients).
•38 percent of the control group, who received the standard two-drug treatment for 48 weeks tested negative for the virus (104 patients).
Patients receiving the low-dose of ribavirin did not fare as well – just 36 percent were virus-free after 48 weeks of treatment.
"Based on this phase 2 study, it appears that if this drug receives final approval approximately two-thirds of patients will be able to be treated successfully with 28 weeks of treatment and one-third will need 48 weeks of treatment, though this will require confirmation from the phase 3 trials, from which preliminary results were recently released," said Dr. Kwo.
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The research was funded by Schering Corp. a division of Merck & Co., which provided assistance with the trial, data collection and analysis, and the manuscript.
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