Zobair M. Younossi, MD discusses "A New Era of Hepatitis C Therapy"

Zobair M. Younossi, MD, the Executive Director of the Center for Liver Diseases and Vice President of Research at the Inova Health System in Falls Church, Virginia discusses the STAT-C drugs and other novel therapies for Hepatitis C from AASLD 2010. Features a video and transcript. Watch and read here.

Vertex adds ribavirin in additional treatment arm in ongoing Phase II VX-222 & Telaprevir combo trial...

-New treatment arm to evaluate all oral, triple combination regimen of telaprevir, VX-222, and ribavirin-

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced plans to enroll an additional treatment arm as part of its ongoing Phase 2 clinical trial evaluating 12-week regimens of Vertex's lead investigational hepatitis C virus (HCV) protease inhibitor, telaprevir, in combination with its lead investigational HCV polymerase inhibitor, VX-222. The planned treatment arm is supported by emerging data from multiple ongoing clinical trials of direct-acting antiviral (DAA) therapies, including the trial of telaprevir/VX-222-based combination therapy, which suggest that adding ribavirin to a DAA treatment regimen may increase antiviral activity. In the additional arm, Vertex plans to evaluate a 12-week combination of three oral therapies — VX-222, telaprevir and ribavirin — dosed twice a day within a response-guided regimen.

"We are encouraged by the high viral cure rates and shorter treatment durations reported in Phase 3 studies of telaprevir-based combination therapy, and we remain focused on continuing to develop new potential treatments for hepatitis C," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "Evaluating a 12-week combination of telaprevir, VX-222 and ribavirin will provide us with important information about the potential for this all-oral regimen that could be taken twice a day."

About the Ongoing Phase 2 Trial of Telaprevir and VX-222

Beginning in August 2010, patients enrolled in the randomized, parallel-group, dose-ranging Phase 2 trial started receiving treatment. The primary endpoint of this trial is to assess safety and tolerability of 12-week telaprevir/VX-222-based combination therapy in people with genotype 1 chronic hepatitis C. A secondary endpoint of this study is to assess on-treatment antiviral activity and the proportion of patients in each study arm who achieve a sustained viral response (SVR; defined as undetectable HCV RNA 24 weeks after the end of treatment). If patients meet response-guided criteria during treatment (undetectable HCV RNA at week 2 and week 8 of treatment), they may be eligible to stop all therapy at 12 weeks.

The study includes treatment arms that are evaluating 12-week, response-guided regimens of two- and four-drug telaprevir/VX-222 combination therapy, given twice daily, with and without Pegasys® (pegylated-interferon alfa-2a) and Copegus® (ribavirin). Trial sites for the two- and four-drug ongoing arms completed enrollment in October 2010. The additional three-drug treatment arm of telaprevir, VX-222 and ribavirin announced today is expected to begin patient enrollment in the first quarter of 2011, pending completion of institutional review board (IRB) approvals and consultation with regulatory agencies. Based on further results from the ongoing treatment arms, Vertex may add an additional arm in this study.

Additional Clinical Trial of VX-222 Combination Therapy

Vertex is also conducting a Phase 2 clinical trial evaluating the safety, tolerability and antiviral activity of VX-222 in combination with pegylated-interferon and ribavirin, which began in August 2010. Enrollment is ongoing and Vertex expects to enroll a total of 50 patients. Patients in this trial will receive one of two doses of VX-222 (400 mg or 750 mg twice daily) in combination with pegylated-interferon alfa-2a and ribavirin for 12 weeks, followed by pegylated-interferon alfa-2a and ribavirin alone for 36 weeks.

About Telaprevir and VX-222

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. Phase 3 studies of telaprevir in combination with pegylated interferon alfa-2a and ribavirin are complete and Vertex is on track to complete its rolling New Drug Application (NDA) submission to the U.S. Food and Drug Administration by the end of 2010.

VX-222 is an investigational, oral, non-nucleoside inhibitor of HCV NS5B polymerase. Vertex added VX-222 to its development pipeline as part of the acquisition of ViroChem Pharma Inc. in March 2009. Vertex retains worldwide commercial rights to VX-222.

About Hepatitis C

Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the liver and 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 their infection.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 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 an increased 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 By 2029, total annual medical costs in the U.S. for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.11

Additional resources for media, including a hepatitis C backgrounder and glossary of common terms, are available at: http://investors.vrtx.com/press.cfm

New Journal article: Forthcoming challenges in the management of STAT-C therapy

New article "Forthcoming challenges in the management of STAT-C therapy" published online in Digestive and Liver Diseases(full article available in PDF format as well). This is the first article I've seen addressing the importance pharmacokinetics in STAT-C therapy and applies some of what we've learned from HIV antiretroviral therapy. Definitely worth a read - Cmin/IC50 ratios DO matter!!

Forthcoming challenges in the management of STAT-C therapy

Raffaele Bruno, Serena Cima, Laura Maiocchi, Paolo Sacchi

Received 22 July 2010; accepted 9 September 2010. published online 27 October 2010.
Corrected Proof

Abstract

Agents that specifically target the replication cycle of the virus [specifically targeted antiviral therapies for hepatitis C (STAT-Cs)] by directly inhibiting the NS3/4A serine protease, the NS5B polymerase and NS5A are currently in clinical development. The need to achieve serum drug concentrations able to suppress viral replication is a key factor for a successful antiviral therapy and the prevention of resistance. Thus pharmacokinetics parameters became important issues for drugs used in the therapy of hepatitis C. The ratio of Cmin/IC50 (inhibitory quotient or IQ) can provide a surrogate measure of a drug's ability to suppress HCV replication, by taking into account the relationship between plasma drug levels and viral susceptibility to the drug. Ritonavir boosting may be a useful strategy to improve pharmacokinetic parameters. Characterising resistance to STAT-Cs in clinical trials is essential for the management of a drug regimen to reduce the development of resistance and thereby maximise SVR rate. The lesson of HIV therapy, provide a compelling case for the exploration of combinations of direct-acting antiviral agents.

GlobeImmune's GI-5005 HCV Therapeutic Vaccine increases SVR by 12% in previous treatment failures

By Liz Jones Hollis (http://www.fiercebiotech.com/node/93538/print)
Created Nov 4 2010 - 6:56am

Phase 2b Study Demonstrates GlobeImmune's GI-5005 HCV Therapeutic Vaccine Increases Sustained Virologic Response by 12 Percent in Patients Who Previously Failed Therapy with Standard of Care.

Additional data suggest that cellular immunity may be a fundamental deficit in hardest-to-treat IL28B T/T genotype patients and is corrected by GI-5005
Data to be presented at annual meeting of the American Association for the Study of the Liver Diseases

LOUISVILLE, Colo., October 30, 2010 - GlobeImmune Inc. today announced additional data from the GI-5005-02 Phase 2b study demonstrating that GI-5005, the Company's investigational Tarmogen® product, improved sustained virologic response (SVR) by 12% in patients with genotype 1 chronic hepatitis C virus (HCV) infection who had failed prior treatment with standard of care (SOC, pegylated-interferon alpha 2a plus ribavirin). This study suggests that GI-5005 may have the potential to be the first successful therapeutic vaccine for patients chronically infected with HCV.
Paul J. Pockros, M.D., of Scripps Clinic will deliver the oral presentation of the results in a late-breaker session at 6 p.m. EDT Monday November 1, 2010 at the 61st Annual Meeting of the American Association for the Study of the Liver Diseases (AASLD) in Boston.

On an intent-to-treat basis (subjects who received at least one dose of combination therapy), prior non-responders receiving GI-5005 plus SOC as a triple therapy had an SVR rate of 17%, compared to an SVR rate of only 5% in patients receiving SOC alone. Prior non-responders in this study were defined as patients who did not clear virus after a minimum of 12 weeks of SOC, including null responders, poor responders, and partial responders. Relapsers and on-treatment breakthroughs were not enrolled in the study. The most common adverse events associated with GI-5005 were injection site reactions that were generally mild and transient in nature. Discontinuation rates due to adverse events in the GI-5005 triple therapy arm were comparable to the discontinuation rates in the SOC alone arm.

"Only 4-7% of patients with genotype 1 HCV who were null, poor or partial responders to their first course of pegylated interferon-based therapy would be expected to achieve a sustained virologic response with a second course of treatment," said Dr. Pockros. "In this study, GI-5005 conferred a three-fold improvement in SVR, an important treatment effect in this challenging patient population."

Additional immunology data from the study will be presented in a poster on Tuesday November 2, 2010 by John M. Vierling, M.D., of Baylor College of Medicine. These data show that GI-5005 improved HCV-specific T cell responses 10-fold over SOC alone in patients with the IL28B T/T genotype (~20% of chronically infected patients), the subgroup most likely to fail treatment with SOC alone. Patients with the IL28B T/T genotype receiving SOC alone had an HCV-specific cellular immune response that was 17-fold lower than patients in the IL28B C/C or C/T subgroups. The improved HCV-specific T cell immunity in IL28B T/T patients receiving GI-5005 plus SOC correlates with previously reported data that demonstrated GI-5005 increased SVR rates by 60 percent in interferon-naïve T/T patients compared to T/T patients receiving SOC alone.

"These data suggest that the fundamental deficit in patients carrying the T allele of the IL28B gene is a deficit in adaptive cellular immunity, the mechanism that GI-5005 was designed to address," said David Apelian, M.D., Ph.D., Chief Medical Officer at GlobeImmune. "We are confident that GI-5005 will become a cornerstone of HCV therapy, particularly for difficult to treat populations, such as IL28B T/T patients."

A 40 patient expansion of this study in patients having the IL28B T/T genotype was initiated last week to further explore the potential treatment effect of GI-5005 in this patient population.

GI-5005 is a therapeutic vaccine candidate designed to generate HCV-specific T-cell responses and improve virologic responses in patients with chronic hepatitis C virus infection.

About GlobeImmune
GlobeImmune Inc. is a private company developing therapeutic vaccines called Tarmogens for the treatment of cancer and infectious diseases. Tarmogens generate activated killer T cells that are designed to locate and eliminate virally-infected cells and/or cancer cells. The Company's lead product candidate, GI-5005, is a Tarmogen being developed for the treatment of chronic hepatitis C virus (HCV) infection. GI-5005 is designed to complement both the current standard of care and emerging novel therapies for HCV. The Company's lead oncology program, GI-4000, targets cancers caused by mutated versions of the Ras oncoprotein. GI-4000 is being investigated in clinical trials for the treatment of pancreas cancer as well as other cancers that contain mutated Ras, including non-small cell lung cancer and colorectal cancer. In May 2009, the Company announced a global partnership with Celgene focused on the discovery, development and commercialization of multiple product candidates for the treatment of cancer.
For additional information, please visit the company's website at www.globeimmune.com.

Boosted HCV proteases in the STAT-C era - what can we learn from HIV?

I'm far from a pharmacologist and nowhere near being an expert in pharmacokinetics, but my rudimentary view, based on this report Jules Levin did on a session addressing ritonavir boosted HCV PIs from the 5th International Workshop on Hepatitis C Resistance and New Compounds last summer in Boston, is that we certainly could learn a thing or two taught from the lessons of boostings past. Boosting HIV protease inhibitors with a sub-therapeutic dose of ritonavir was a break through in the fight against HIV. Boosted PIs allowed for a 'PK cushion' when it came to trough levels... that is, when the PI was at its lowest concentration in the body - usually just before the next dose - it was still well above the IC50 of the virus thanks to the metabolic inhibition provided by ritonavir. This cushion prevented sub-therapeutic levels of the drug which could lead to viral resistance. As an added benefit, this also allowed for less frequent dosing and a sometimes drastic reduction in pill count - hopefully, one could argue - leading to an improvement in patient adherence. The dark side of ritonavir boosting is the remote possibility that even a sub-therapeutic dose could lead to the development of HIV resistance, tolerability is still an issue, increased trigylcerides, kidney toxicity and the fact that an essential metabolic enzyme, CYP 450, an enzyme responsible for the metabolism of many common drugs, not just HIV protease inhibitors, was effectively being inhibited as long as the patient was on therapy. Drug-drug interactions are a major problem in boosted PI HIV therapy, and will continue to be.

So all of the above might be applicable to ritonavir-boosting of HCV protease inhibitors as well… at least some of them. Telaprevir, despite what was shown in vitro, doesn’t respond to ritonavir boosting in vivo, at least for the long haul. Experts are still speculating on the exact reasons why – perhaps an inhibition/induction mechanism on the part of Telaprevir or some secondary mechanism of metabolism. The good news is that some initial data shows Telaprevir may not actually need to be boosted in a majority of patients, still showing some remarkably good mean concentration levels at trough even with q12h dosing. What still hasn’t been shown – at least to my knowledge – is the range of intra-patient variability from that mean. From the HIV PI history books, we know that there is usually a wide range of variability when it comes to pharmacokinetics dependent on a range of host factors. Even though it looks like HCV resistance might not mean a whole lot in the long run - the jury is still out – if the risk of being on the wrong end of that PK curve can be avoided, then it should certainly be a priority to do so.

Danoprevir and ABT-450, among others, are HCV protease inhibitors that appear to benefit from ritonavir boosting or even require it. In fact, Roche changed the dosing in their INFORM-2 Phase I trial of Danoprevir to include ritonavir boosting - but we need to see more data before the final judgment. Where the therapies for HIV and HCV differ, however, is that the HCV patient will only be on a boosted PI regimen for a short period of time, vs the HIV patient who is on the drug indefinitely so some of the long term metabolic effects of being on a boosted PI may be avoided. Still, drug-drug interactions are a concern as is the safety of a patient on a boosted HCV protease inhibitor with renal and/or liver insufficiency.

Could the benefits outweigh the risks in using ritonavir to boost HCV PIs? It’s definitely a tough call at this point and any judgment would be highly theoretical given the relative shortage of data in this area. As new data emerges, we’ll get a better idea of any clinical benefit or potential safety risks for the HCV patient in this brave new era of STAT-C therapy. My semi-educated gut feeling is that boosted PIs will offer some benefit with providing a “PK cushion” thus a leg-up in preventing resistance… but will that be enough to actually prevent resistance given a rapidly replicating virus that can make every conceivable combination of mutations in the course of one day? Does a boosted HCV PI plus a nuc or non-nuke backbone present enough of a barrier to prevent resistance given the variables such as intra-patient PK variability, drug interactions and adherence issues? Will interferon and ribiviran still be needed to shore-up any gaps left by STAT-C therapy? How about next generation metabolic blockers like Gilead's Cobicistat now in development? Only time - and solid empirical data - will tell.

Regulus Therapeutics receives $500,000 in grants to develop microRNA therapeutics to treat HCV & fibrosis....

From the PharmaLive.com News Archive - Nov. 03, 2010
LA JOLLA, Calif.--(BUSINESS WIRE)--Nov 3, 2010 - Regulus Therapeutics Inc. announced today that it has been awarded two grants totaling $488,989 under the Federal government's Qualifying Therapeutic Discovery Project Program. The Qualifying Therapeutic Discovery Project Program was created to support research with the potential to produce new therapies and create high paying jobs. The grant funding will support preclinical development of Regulus' novel microRNA approaches to treat Hepatitis C Virus infection and fibrosis.

“We are pleased to receive maximum awards for both of the applications we submitted to this program,” said Zachary A. Zimmerman, Ph.D., Director of Business Development at Regulus. “The funding provides access to non-dilutive capital supporting the advancement of our preclinical microRNA programs toward the clinic.”

The Qualifying Therapeutic Discovery Project Program provides an immediate boost to the U.S. biomedical research community through targeted support of projects that have the potential to produce new therapies, address unmet medical needs and create jobs.

About microRNAs

The discovery of microRNA in humans is one of the most exciting scientific breakthroughs in the last decade. microRNAs are small RNA molecules, typically 20 to 25 nucleotides in length that do not encode proteins but instead regulate gene expression. Nearly 700 microRNAs have been identified in the human genome, and more than one-third of all human genes are believed to be regulated by microRNAs. As a single microRNA can regulate entire networks of genes, these molecules are considered the master regulators of the genome. microRNAs have been shown to play an integral role in numerous biological processes including the immune response, cell-cycle control, metabolism, viral replication, stem cell differentiation and human development. Most microRNAs are conserved across multiple species indicating the evolutionary importance of these molecules as modulators of critical biological pathways. Indeed, microRNA expression or function has been shown to be significantly altered in many disease states, including cancer, heart failure and viral infections. Targeting microRNAs with anti-miRs, antisense oligonucleotide inhibitors of microRNAs, or miR-mimics, double-stranded oligonucleotides to replace microRNA function, opens the possibility of a novel class of therapeutics and a unique approach to treating disease by modulating entire biological pathways. To learn more about microRNAs please visit http://www.regulusrx.com/microrna/microrna-explained.php

About Regulus Therapeutics Inc.

Regulus Therapeutics is a biopharmaceutical company leading the discovery and development of innovative new medicines targeting microRNAs. Regulus is using a mature therapeutic platform based on technology that has been developed over 20 years and tested in greater than 5,000 human subjects. In addition, Regulus works with a broad network of academic collaborators and leverages oligonucleotide drug discovery and development expertise from its founding companies Alnylam Pharmaceuticals (Nasdaq:ALNY) and Isis Pharmaceuticals (Nasdaq:ISIS). Regulus is advancing microRNA therapeutics towards the clinic in several areas including hepatitis C infection, immuno-inflammatory diseases, fibrosis, oncology, and cardiovascular/metabolic diseases. Regulus' intellectual property estate contains both the fundamental and core patents in the field and includes over 600 patents and more than 300 pending patent applications pertaining primarily to chemical modifications of oligonucleotides targeting microRNAs for therapeutic applications. In April 2008, Regulus entered into a major alliance with GlaxoSmithKline to discover and develop microRNA therapeutics for immuno-inflammatory diseases. In February 2010, Regulus entered into a new collaboration with GlaxoSmithKline to develop and commercialize microRNA therapeutics targeting microRNA-122 for the treatment of Hepatitis C Viral infection. In June 2010, sanofi-aventis and Regulus entered into the largest-to-date strategic alliance for the development of microRNA therapeutics. This alliance is focused initially on fibrosis. For more information, visit http://www.regulusrx.com

Biolex presents positive tolerability data of Locteron vs Peg-Intron at AASLD...

Market Wire - Nov. 01, 2010

PITTSBORO, NC -- (MARKET WIRE) -- 11/01/10 -- Biolex Therapeutics, Inc. today announced positive results from two Phase 2b trials further demonstrating the strong anti-viral response and tolerability advantages of the 480 µg dose of Locteron® in the treatment of hepatitis C. In the Phase 2b trials, patients directly reported flu-like adverse events on a daily basis through an electronic patient-reported outcome (ePRO) system, and the results demonstrated a statistically significant reduction in the frequency and severity of flu-like adverse events and reduced use of concomitant (analgesic/antipyretic) medications for patients treated with Locteron compared to patients treated with the PEG-Intron® control. Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently marketed interferons as a core component of combination therapies for the treatment of hepatitis C. These advantages include reduced flu-like symptoms, reduced rates of depression, and a less frequent dosing regimen with half the number of injections. The "EMPOWER" Phase 2b ePRO results will be presented today in a late-breaker session at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.

EMPOWER is a prospectively designed analysis of the combined results from two Phase 2b hepatitis C trials focusing on the 480 µg dose of Locteron (the middle dose of three Locteron doses evaluated in the two trials). Through 12 weeks of treatment, 50% of the patients in the Locteron 480 µg group achieved cEVR (undetectable HCV RNA) compared to 46% of the patients in the PEG-Intron group. As a result of its controlled-release mechanism, Locteron achieved strong efficacy results while being dosed half as frequently as PEG-Intron.

The AASLD presentation today includes for the first time results from the ePRO adverse-event reporting system where patients directly recorded their flu-like adverse events on a daily basis, providing greater insight into the patients' real world experiences with these side effects and the impact on their daily activities. In addition to the self-reporting by patients with the ePRO system, flu-like adverse events were also recorded using traditional weekly adverse event assessments performed by the clinical sites. Flu-like adverse events were predefined to include arthralgia, chills, fever, headache, and myalgia.

A substantial reduction in flu-like adverse events for patients treated with Locteron compared to PEG-Intron was evident even in the first week after initiation of treatment and continued through the 12-week time point through which the ePRO system was utilized. The reduction in flu-like adverse events during the week after the first injection supports the hypothesis that the slower rise to Cmax provided by the controlled-release mechanism of Locteron contributes to the tolerability advantages seen in multiple clinical trials. A comparison of the flu-like adverse event reporting by the clinical sites and by ePRO provide independent confirmation of the substantial benefits Locteron provided in reducing these side effects as outlined in the table below:


Locteron Reduction in Flu-Like Adverse Events (Week 1)
---------------------------------------------------------
Total Events Moderate and Severe Events
---------------------------- ----------------------------
Clinical Site Patient (ePRO) Clinical Site Patient (ePRO)
Reporting Self-Reporting Reporting Self-Reporting
------------- -------------- ------------- --------------

Locteron Reduction 50% 51% 70% 39%
In Flu-Like Adverse Reduction Reduction Reduction Reduction
Events Compared to
PEG-Intron

"The ePRO results being presented for the first time today are robust and provide important insight into the impact that flu-like adverse events have on patients' daily lives," said Patrick Marcellin, MD, PhD, Professor of Hepatology at the University of Paris and Head of the Viral Hepatitis Research Unit in Hôpital Beaujon, Clichy. "Treatment of hepatitis C is likely to progress to triple and quad therapies in which interferons are combined with one or more direct-acting anti-viral drugs. Locteron's advantages with regards to flu-like adverse events, depression and dosing frequency have the potential to enhance the overall tolerability of, and patient adherence to, these future combinations."

Consistent with the reduction in flu-like adverse events, less than half as many Locteron patients used concomitant medications (analgesics and antipyretics) compared to the usage of these medications by PEG-Intron patients during the study period as detailed below.


Percentage of Patients Using
Concomitant Medications
-----------------------------------------
Locteron
480 µg PEG-Intron
-------------------- --------------------

Patients Using Analgesics 27% 59%
Patients Using Antipyretics 23% 49%

A comparison of the ePRO and clinic site reporting highlights the fact that flu-like adverse events may even be more important to patients than historically believed. The total flu-like adverse events reported directly by the patients using the ePRO system during the first 12 weeks of EMPOWER was more than four times greater than the total flu-like adverse events recorded by the clinical sites. Also of importance, patients rated 80% of their flu-like adverse events as moderate or severe in their ePRO reports, compared to the clinical site reporting in which only 13% of flu-like adverse events were rated as moderate or severe. Despite the apparent differences in sensitivity in the two adverse event reporting methods, the results from both the ePRO and weekly clinic visits independently confirm the reduction in flu-like adverse events for patients treated with Locteron compared to patients treated with PEG-Intron. Through the 12-weeks, the difference in flu-like adverse event counts was statistically significant when measured by both the ePRO and clinical site reporting methods (p < 0.001 for each).

The relevance of flu-like adverse events was highlighted in a survey of hepatitis C patients published in the Journal of Viral Hepatitis in June 2010 in which depression and flu-like symptoms were cited as the two most important adverse events impacting patient adherence to treatment. Last week Biolex reported 48-week results from its SELECT-2 Phase 2b trial of Locteron demonstrating substantial reductions in depression compared to PEG-Intron.

AASLD Presentation
The EMPOWER ePRO and clinical-site tolerability results will be presented today by the lead author, Walker Long, MD, Chief Medical Officer and Vice President, Drug Development, Biolex Therapeutics, in the form of a poster titled "Adverse Event Reporting During HCV Treatment Via Weekly Clinic Visits Substantially Underestimates Flu Frequency & Severity Compared to Daily ePRO: Results From 133 Patients in EMPOWER."

"The EMPOWER results are notable in that they show a statistically significant reduction of flu-like adverse events for Locteron confirmed by two sources, the clinical site assessments and the daily patient reporting of side effects through the ePRO System. The reductions in the percent of patients using analgesics and in overall analgesic use observed in the Locteron group provide additional support for improved tolerability on Locteron," said Dr. Long. "These results complement the positive results released last week from our SELECT-2 Phase 2b trial in which we showed statistically significant reductions in flu-like adverse events for three different Locteron doses, and substantial reductions in depression for the Locteron 480 and 320 µg doses."

About EMPOWER Study
The objective of the EMPOWER study was to test the hypothesis that the 480 µg dose of Locteron dosed once every two weeks reduces flu-like symptoms but retains equivalent efficacy compared to PEG-Intron (1.5 µg/kg, administered every week). The 133 patients in the EMPOWER study were enrolled in two contributing Phase 2b trials:

* SELECT-2, a Phase 2b dose-finding trial evaluating the 320, 480 or 640 µg doses of Locteron versus PEG-Intron.
* The 480 STUDY, a Phase 2b trial evaluating the 480 µg dose of Locteron versus PEG-Intron.

All patients in both trials were treatment-naïve-genotype-1 subjects with chronic hepatitis C, and all patients were also treated with weight-based ribavirin. A total of 30 sites participated in the two trials (14 sites in the US, 11 in Europe, and five in Israel).

Locteron Overview
Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently approved products, including reduced flu-like symptoms and rates of depression, and cutting in half the number of injections required. In contrast to Locteron, the currently approved products, Pegasys® and PEG-Intron, are immediate-release products that lack a controlled-release mechanism. The two-drug combination of interferon alpha and ribavirin serves as the current standard of care for the treatment of hepatitis C. The launch of the first direct-acting anti-viral (DAA) product, projected for 2011, will transform treatment of genotype-1 patients to a triple-drug therapy (interferon plus ribavirin plus DAA) and substantially raise cure rates. Other recent triple or quad drug combinations with interferon (including interferon plus ribavirin plus two DAA agents) have shown promise in early clinical testing, further solidifying the continued role of interferon in the treatment of hepatitis C. It is estimated that worldwide sales of interferon products for the treatment of hepatitis C will approach $6 billion by 2016.

Locteron incorporates an advanced controlled-release drug delivery technology that allows dosing once every two weeks, more convenient than Pegasys and PEG-Intron, each of which require dosing every week. More importantly, Locteron's controlled-release mechanism results in the gradual release of interferon alpha 2b to patients over the duration of two weeks and avoids the early peak plasma levels of the active interferon that characterize the pegylated interferons. This controlled-release mechanism is designed to reduce the frequency and severity of flu-like symptoms and depression commonly experienced by patients treated with pegylated interferons.

Locteron is an investigational therapeutic candidate and has not been approved for sale by the United States Food and Drug Administration or by any international regulatory agency.