March 14, 2011

A wild ride in Hepatitis C treatment

A wild ride in Hepatitis C treatment: Vertex stock gives investors whiplash

March 14th, 2011 5:56 pm ET

Elisabeth Morris
Boston Health News Examiner
 
Has anyone noticed that Vertex Pharmaceuticals, Cambridge MA (VRTX, Nasdaq) stock has been bouncing around like a ping pong ball during the last months? Traders have been consistently excited about the positive news from Vertex’s Hepatitis C virus (HCV) treatment telaprevir. And some news about a treatment for cystic fibrosis pushed the stock to it’s 52 week high on March 4. But investors reacted (or should we say over-reacted) quite strikingly to some extremely early, positive (but as yet unpublished) results from a very short and small study testing efficacy of Pharmaset’s Hepatitis C treatment, and Vertex’s stock lost 12% of it’s value abruptly last week. Now Vertex stock is undergoing a small uptick based on positive results from it’s anti-inflammatory to treat epilepsy. What a roller coaster ride! It is really very unlikely that any of these results justify such large changes in the value of the company’s stock.

Let’s go back to telaprevir, the treatment for Hepatitis C that is the foundation of Vertex’s value at this point. Hepatitis C virus is a leading cause of chronic liver disease in the United States, and it is estimated that 170 million people worldwide have clinical signs from Hepatitis C virus infection. HCV can cause acute liver disease with severe symptoms, but about 75% of patients develop chronic HCV which can vary from asymptomatic to chronic liver failure and cirrhosis over a course of 10-20 years. HCV is a enveloped, single stranded RNA virus which infects liver cells, proliferates in the cell and then goes on to infect many more cells with each replication process. The end result is destruction of the liver. The viral replication process requires the virus to make an enzyme called NS3/4A. When telaprevir is in the circulation, it binds to the NS3/4A enzyme and prevents the virus from proliferating in the liver cell.

Present standard of care for Hepatitis C infection is a combination therapy of pegylated interferon alpha plus ribavirin for 24-48 weeks. Approximately 70-80% of patients infected with Hepatitis Virus type 2 and type 3 respond to this treatment, whereas Hepatitis Virus type 1 is only successfully treated in 40% of patients. Success is measured as ‘sustained virological response’ or SVR, where the virus is undetectable 24 weeks after therapy has ended. The treatment plan for telaprevir is to add it to the combination of interferon and ribavirin, and the desired result is an improvement in the per cent of patients with SVR in Hepatitis Virus type 1 patients previously untreated. In addition, Vertex investigated whether treatment of patients who did not respond to interferon and ribavirin, or who responded and then relapsed would achieve SVR by repeat treatment with the addition of telaprevir.

Vertex filed a NDA in November 2010, and was granted a 6 month priority review by the FDA, which reduced the time for the FDA to evaluate the submission from 10 months to 6 months. The data in the NDA was based on three studies. Two recruited people never before treated for Hepatitis C and treated them with a combination of pegylated interferon, ribavirin and telaprevir. 75% achieved a viral cure (SVR) with telaprevir-based combination therapy, compared to 44% of people who received pegylated-interferon and ribavirin alone; The data showed there was no benefit to extending total treatment from 24 weeks to 48 weeks in people who responded quickly, so treatment time was cut in half for many patients. The third study was done in people with hepatitis C who had not achieved a viral cure with a prior course of treatment. 83% of prior relapsers and 29% of prior non-responders achieved a viral cure with telaprevir-based combination therapy compared to 24%, and 5% of people in these subgroups, respectively, who received pegylated-interferon and ribavirin alone. This result, in particular, is quite exciting, as prior to the availability of telaprevir, non-responders or relapsers had only a tiny hope of improved response with a second course of ribavirin/pegylated interferon therapy. In March, Vertex reported that telaprevir helped eliminate the hepatitis C virus in 70 percent of patients who were also infected with HIV, according to interim analysis from a small midstage clinical trial. The interim analysis looked for a rapid viral response (RVR), meaning the hepatitis C virus was undetectable in the blood after four weeks of treatment.

Vertex has stiff competition from Merck, who also filed an NDA for boceprevir for treatment of Hepatitis C in studies designed similarly to those for telaprevir. Boceprevir has the same mechanism of action against the Hepatitic C virus as telaprevir. Efficacy was similar for boceprevir and telaprevir, but Merck is grappling with anemia as a side effect of boceprevir, and the anemia is severe enough to require treatment with recombinant erythropoietin. Although more than 20 other drugs are in development for Hepatitis C, the advanced state of telaprevir and boceprevir, and the good results with both will require that any new drugs differentiate themselves by complete elimination of the virus, or an advance that would not require combination with pegylated interferon and ribavirin, both of which cause clinically important side effects.

Back to Vertex and it’s wild stock ride. In May 2009, Vertex stock was trading at $29, and it slowly rose to $37 in May 2010 after phase 2 results for telaprevir were reported. The stock hit $47 after the filing of the NDA and then the release of the recent study in patients co-infected with Hepatitis C and HIV. In February Vertex released some results for VX-770, a genetic treatment for 4% of cystic fibrosis patients (1) with a genetic mutation known as G551D. Patients with the G551D mutation have sufficient cystic fibrosis transporter proteins on the surface of cells but the proteins are damaged and don't work correctly. VX-770 is a "potentiator" designed to improve the function of the damaged CFTR proteins, thereby fixing the root cause of cystic fibrosis in these patients. Although this drug will be targeted to a very small subpopulation of cystic fibrosis patients, those with the gene mutation G551D sustained a 10.6% improvement in lung function. Vertex had designated a 4.5% improvement as a positive endpoint for this study, so these results are solidly positive. Based on this result, Vertex’s stock rose to a 52 week high of 51.07 on March 4.

Just last week, at the International Liver Congress in Berlin, Pharmaset, a Princeton, NJ biotech company presented a poster which claimed that combination therapy with 2 nucleotide analogs resulted in 95-100% of patients with no detectable Hepatitis C virus 4 weeks after initiation of treatment. While quite promising, this type of viral therapy has been around since the development of AZT which was approved by the FDA for treatment of HIV in 1987. While Pharmaset’s dual therapies demonstrated increased efficacy compared to treatment with either drug alone, the study reported results in only 30 patients. Nucleotide analogs are well understood, and typically induce viral resistance with sustained use. The use of 2 different analogs together may circumvent this problem, but much longer studies are needed to be able to predict the success of the Pharmaset drugs for treatment of Hepatitis C. But this study does generate excitement centered around the fulfilling of the 2 remaining goals for Hepatitis C virus treatment: Complete elimination of the virus, and removal of requirement for treatment with interferon and ribavirin. But based on this very early, very short study in 30 patients, Vertex’s stock plummeted 12% to $44.80 on March 10. It is way too premature to predict what effect the Pharmaset drugs will have on the market for telaprevir.

Luckily, on that same day, Vertex fought back by releasing positive safety and tolerability goals in a midstage study of an anti-inflammatory for treatment-resistant epilepsy, a type of epilepsy where seizures start and occur in a specific part of the brain. The study enrolled and dosed people who had not benefitted from the use of at least two currently available medicines. While the drug was safe, efficacy was not significant. But, greater improvements were observed in the last two weeks of the treatment phase and first two weeks of the follow-up period, which suggests that a longer-duration study may be needed to evaluate the effectiveness of the drug. Vertex expects to begin this study as early as the fourth quarter.

Source
Gastroenterology
Volume 140, Issue 3 , Pages 809-817, March 2011

Tinsay A. Woreta, Catherine G. Sutcliffe, Shruti H. Mehta, Todd T. Brown, Yvonne Higgins, David L. Thomas, Michael S. Torbenson, Richard D. Moore, Mark S. Sulkowski

Received 24 May 2010; accepted 22 November 2010. published online 06 December 2010.

Abstract

Background & Aims
Hepatic steatosis is a common histologic finding in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), although little is known about its natural history. We prospectively examined the natural history of steatosis in patients coinfected with HIV and HCV who attended an urban HIV clinic.

Methods
The study cohort consisted of 222 coinfected patients (87% black, 94% with HCV genotype 1 infection) who had at least 2 liver biopsies performed between 1993 and 2008. Biopsy specimens were scored by a single pathologist; samples were classified as having trivial (<5% of hepatocytes affected) or significant (>5%) levels of fat (steatosis). We characterized progression to significant levels of fat among patients whose first biopsy samples had no or trivial levels of fat, and regression among those with significant fat, using logistic regression.

Results
Initial biopsy specimens from most patients (88%) had no or trivial amounts of fat. Among second biopsy samples, 74% had no or trivial fat and 13% had significant amounts of fat. The strongest risk factors for progression of steatosis were alcohol abuse and overweight/obesity; cumulative exposure to antiretroviral therapy between biopsies and high counts of CD4+ T cells were associated with reduced progression of steatosis. Among the 28 patients whose initial biopsy specimen had significant fat levels, most (75%) regressed.

Conclusions
Antiretroviral therapy and high counts of CD4+ T cells are associated with reduced progression of steatosis in patients coinfected with HIV and HCV. Efforts to diagnose and prevent steatosis should focus on persons with a high body mass index and excessive alcohol intake.

Keywords: Pathology, Cirrhosis, AIDS, Liver Disease

Source

FDA Panel To Review Merck, Vertex Hepatitis Drugs In Late April

March 14, 2011, 11:52 A.M. ET

By Thomas Gryta
Of DOW JONES NEWSWIRES

NEW YORK (Dow Jones)--A U.S. Food and Drug Administration panel will review two hepatitis C drugs in development from Vertex Pharmaceuticals Inc. (VRTX) and Merck & Co. Inc. (MRK) in late April, as the companies race to compete against each other in a potentially lucrative market.

The agency's Antiviral Drugs Advisory Committee will review Merck's boceprevir on April 27 and Vertex's telaprevir on April 28. The widely expected reviews will have outside experts recommend whether the agency should allow the drugs on the market.

Both drugs have shown success in increasing the cure rates of the liver disease when added to current treatments.

They are expected to come to the market at similar times and be widely used, creating a market share battle. Merck said in early January that it was granted a six-month review; Vertex is getting a similar review and expects a decision by May 23.

Many on Wall Street believe that clinical trials show Vertex's telaprevir is the preferable drug, although Merck's Chief Executive Kenneth Frazier has repeatedly stated his confidence in boceprevir's prospects.

Wells Fargo recently projected $1.4 billion in U.S. sales next year for telaprevir. Vertex owns the North American rights to the drug and would get a royalty on overseas sales from partner Johnson & Johnson (JNJ).

Hepatitis C is a blood-transmitted virus that causes liver inflammation and can lead to cirrhosis, cancer and liver failure.

Both the Merck and Vertex drugs are known as protease inhibitors, which are designed to block an enzyme that helps the hepatitis C virus replicate. Standard treatment is a combination of the drug pegylated interferon and ribavirin, but adding the new drugs may improve cure rates and shorten the duration of treatment.

- By Thomas Gryta, Dow Jones Newswires; 212-416-2169; thomas.gryta@dowjones.com

Source
March 14, 2011 03:00 AM Eastern Daylight Time

INGELHEIM, Germany--(BUSINESS WIRE)--For Non- U.S. Media only

New data from the Boehringer Ingelheim hepatitis C virus (HCV) portfolio will be presented in oral scientific sessions at the International Liver CongressTM 2011, the 46th Annual Meeting of the European Association for the Study of the Liver (EASL), taking place 30 March-3 April in Berlin, Germany. The data will include final results from SILEN-C1 and SILEN-C2, two Phase IIb studies evaluating one of Boehringer Ingelheim’s investigational compounds for Hepatitis C treatment, the once-daily, oral protease inhibitor BI 201335 in combination with the current standard-of-care (pegylated-interferon and ribavirin).

Oral presentations (Friday, 1 April, 2011; Parallel Session: HCV Drug Development, Hall 1)

• SILEN-C1: Sustained Virologic Response (SVR) and safety of BI201335 combined with peginterferon alfa-2a and ribavirin (P/R) in treatment-naïve patients with chronic genotype 1 HCV infection
(Abstract 60. M. Sulkowski, et al. 16:00h - 16:15h)

• SILEN-C2: Sustained Virologic Response (SVR) and safety of BI201335 combined with peginterferon alfa-2a and ribavirin (P/R) in chronic HCV genotype-1 patients with non-response to P/R
(Abstract 66. M. Sulkowski, et al. 17:30h - 17:45h)

Boehringer Ingelheim is continuing its long heritage in virology and is dedicated to developing new medicines to improve treatment for HCV patients. BI 201335 is part of a growing HCV portfolio that is being investigated with the aim of identifying a simpler HCV cure, overcoming the challenges of current treatments.

Additional HCV studies to be presented at EASL

• SVR and Pharmacokinetics of the HCV protease inhibitor BI201335 with PegIFN/RBV in HCV genotype-1 patients with compensated liver cirrhosis and non-response to previous PegIFN/RBV
(Poster 1231. S. Pol, et al.; Saturday, 2 April, 2011, 09:00h - 18:00h)

• Mechanisms of isolated unconjugated hyperbilirubinemia induced by the HCV NS3/4A protease inhibitor BI201335 (Poster 1236. R. Sane, et al.;Saturday, 2 April, 2011, 09:00h - 18:00h)

• BI201335 Pharmacokinetics and early effect on viral load in HCV genotype-1 patients
(Poster 1249. C. Yong, et al.;Saturday, April 2, 2011, 09:00h - 18:00h)

• Preclinical Characterization of the hepatitis C virus NS5B polymerase non-nucleoside inhibitor BILB 1941 (Poster 1215. G. Kukolj et. al.; Friday, 30 March, 2011, 09:00h - 18:00h)

The abstracts can be accessed through the EASL website, http://www.easl.eu/.

For more information on BI’s hepatitis portfolio, please visit www.boehringer-ingelheim.com and follow us on Twitter. www.twitter.com/boehringer.

Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

Within the company’s global research network, Virology is one of the seven R&D areas with focus on Hepatitis C.

In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro (US $17.7 billion) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.

Contacts

Boehringer Ingelheim GmbH
Julia Meyer-Kleinmann
Director Corporate Communications
55216 Ingelheim/Germany
Phone: + 49 - 6132 – 77 8271 / Fax: + 49 - 6132 – 77 70 77
E-mail: press@boehringer-ingelheim.com

Source
In Phase I trial 83% of patients showed undetectable hepatitis C virus levels

BLUE BELL, Pa., March 14, 2011 /PRNewswire/ -- Inovio Pharmaceuticals, Inc. (NYSE Amex: INO), a leader in the development of therapeutic and preventive vaccines against cancers and infectious diseases, announced today that its partner, ChronTech Pharma AB (formerly Tripep AB), has initiated a Phase IIb clinical study of its ChronVac-C® DNA vaccine for hepatitis C virus (HCV), delivered by Inovio's proprietary electroporation DNA vaccine delivery technology, in combination with standard of care.

In a Phase I clinical trial of ChronVac-C using Inovio's MedPulser® electroporation device the therapy resulted in a robust increase in T-cell immune responses against HCV and was safe and well-tolerated. Post-study observation of subjects who completed the protocol and then entered into standard of care (SOC) treatment using interferon and ribavirin showed a complete and rapid viral response (four weeks) in 70% of those participants (5 of 7 patients). More significantly, 83% of the participants (5 of 6 patients) who were monitored for an extended period of time, continued to be free of the virus six months after they completed SOC. SOC treatment alone usually results in about 40-50% of patients reaching undetectable virus levels after six months of treatment.

This Phase II follow-on trial is an open-label, single-dose, randomized trial of 32 patients to further explore the effect of the ChronVac-C® DNA vaccine administered by Inovio's MedPulser® electroporation delivery device. The therapy will be given two times, with four weeks in between, followed by SOC treatment after the final vaccine dose in treatment-naïve chronic HCV infected genotype-1 subjects. This trial will assess the level of immune responses, levels of HCV viral load, and further assess the response to the delivery technology. Twenty patients will receive ChronVac-C® vaccine delivered with Inovio's electroporation device; the 12-patient comparison group will receive standard-of-care treatment alone. The study has received approval from the Swedish Medical Products Agency and local ethical committee.

"If we can repeat the Phase I results in this phase IIb study there is certainly a possibility that vaccination with ChronVac-C® before drug therapy could become a part of the standard of care therapy for patients with chronic hepatitis C-virus infection. In particular, we hope that vaccination with this novel therapy will result in a considerable shortening of the duration of interferon and ribavirin treatment," said Anders Vahlne, CEO of ChronTech Pharma AB.

Dr. J. Joseph Kim, Inovio's president and CEO, said: "We are encouraged by the phase I results showing the improved cure rate in patients who received the HCV vaccine followed by a SOC drug therapy. Any improvement to the HCV standard of care response rates would be well-received by HCV patients and practitioners. We are pleased to collaborate in this advancement of ChronVac-C®, using Inovio's innovative delivery technology, into Phase II."

About Hepatitis C Virus

Hepatitis C virus (HCV) infection is the most common chronic blood borne infection in the United States, where approximately 3.5 million persons have been chronically infected. Worldwide, about 300 million people have been infected with HCV. Based on current statistics for hepatitis C, it is estimated that 8,000 to 10,000 people die each year from chronic liver disease caused by this condition. Chronic HCV infection is the leading indication for liver transplants in the United States. Total health costs associated with hepatitis C virus in the U.S. are estimated at more than $15 billion per year. No vaccine for HCV is currently available.

About Inovio's Electroporation-Based Delivery Technology

Inovio's electroporation-based DNA delivery systems can increase the cellular uptake of an agent by 1,000 times or more. When used to deliver DNA vaccines, Inovio's systems can increase levels of gene expression (i.e. production of the coded protein) and immune responses by 100 times or more compared to plasmid DNA delivered without other delivery enhancements. Inovio has recently reported best-in-class immune responses with DNA vaccines for cervical dysplasias/cancers and HIV. Inovio has also shown the safety and tolerability of its electroporation devices in many hundreds of patients and continues to advance device innovations to further enhance the utility of these devices for mass vaccinations.

About Inovio Pharmaceuticals, Inc.

Inovio is developing a new generation of vaccines, called DNA vaccines, to treat and prevent cancers and infectious diseases. These SynCon™ vaccines are designed to provide broad cross-strain protection against known as well as newly emergent strains of pathogens such as influenza. These vaccines, in combination with Inovio's proprietary electroporation delivery devices, have been shown to be safe and generate significant immune responses. Inovio's clinical programs include HPV/cervical dysplasia and cancer (therapeutic), avian flu (preventive), and HIV vaccines (both preventive and therapeutic). Inovio is developing universal influenza and other vaccines in collaboration with scientists from the University of Pennsylvania. Other partners and collaborators include Merck, National Cancer Institute, U.S. Military HIV Research Program, NIH, HIV Vaccines Trial Network, University of Southampton, and PATH Malaria Vaccine Initiative. More information is available at http://www.inovio.com/.

* * *

This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs (including, but not limited to, the fact that pre-clinical and clinical results referenced in this release may not be indicative of results achievable in other trials or for other indications, that the studies or trials may not be successful or achieve the results desired, that results from one study may not necessarily be reflected or supported by the results of other similar studies and that results from an animal study may not be indicative of results achievable in human studies), the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that the company and its collaborators hope to develop, evaluation of potential opportunities, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, our ability to successfully integrate Inovio and VGX Pharmaceuticals, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2009, our Form 10-Q for the nine months ended September 30, 2010, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.

CONTACTS:

Investors: Bernie Hertel, Inovio Pharmaceuticals 858-410-3101 bhertel@inovio.com

Media: Jeff Richardson, Richardson & Associates 805-491-8313 jeff@richardsonglobalpr.com

SOURCE Inovio Pharmaceuticals, Inc.

RELATED LINKS
http://www.inovio.com/

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Also See: An unusually high cure rate recorded after ChronVac-C® vaccination followed by standard treatment in patients with genotype 1 chronic hepatitis C
Published on March 14, 2011 at 10:22 AM

The EASL International Liver Congress is an opportunity for over 6,000 clinicians and scientists from around the world to hear the latest research, perspectives and treatments for liver diseases from principal experts in the field. It features a high-calibre and multi-disciplinary scientific programme covering groundbreaking information and in-depth examination of the most essential topics.

EASL will hold an international press conference and two morning news briefings during its International Liver Congress 2011 in Berlin.

EASL Press Conference

Date: Thursday 31st March 2011
Time: 11:00am - 12:00am
Location: Room 43

Leading experts will highlight new developments in the future management of viral hepatitis C. A question and answer session will follow the presentations.

Speakers will also be available for informal discussions and interviews following the presentations.

Due to limited space, please confirm your attendance at the press conference with the EASL press office now.

Morning News Briefings

To ensure you get the best out of ILC, news briefings will be held to provide you with the latest news and data on the following topics

Friday 1st April - Liver transplantation & Wilson's disease
Saturday 2nd April 2011 - Hepatocellular carcinoma & Fatty liver disease

Times: 8:00am - 8:45am
Location: The Press Centre

Onsite Press Office staff will be able to assist you in organising interviews with the relevant experts. Wi-Fi access will be available in the press working room.

• Abstracts can be viewed at: http://www1.easl.eu/easl2011/program/Orals/

• Details of the scientific programme are available at: http://www2.kenes.com/liver-congress/scientific/Pages/Timetable.aspx

• Stay up-to-date with all of the latest news and information, follow us @ILCpress!

Source: European Association for the Study of the Liver

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