Bristol-Myers hepatitis C treatment cures up to 90 percent: study

By Bill Berkrot
Thu Apr 10, 2014 7:02am EDT

(Reuters) - A combination of two anti-viral drugs developed by Bristol-Myers Squibb Co cured 90 percent of previously untreated hepatitis C patients and 82 percent of those who failed to respond to prior therapy, according to results from a late stage study presented on Thursday.

The Phase III trial of more than 700 patients called Hallmark-Dual tested a combination of Bristol's daclatasvir and asunaprevir over 24 weeks of therapy in patients with genotype 1b of the virus that causes progressive liver disease.

The cure rate was also 82 percent among patients unable to tolerate treatment with the older standard drugs interferon and ribavirin and 84 percent in patients who had cirrhosis, which accounted for nearly a third of those in the trial.

Patients for whom the virus was undetectable in the blood 12 weeks after completing 24 weeks of treatment were deemed to have achieved sustained virologic response (SVR), which is considered cured.

"Not only was the daclatasvir and asunaprevir regimen highly effective among study participants, it was also very well tolerated, even among sicker patients with more advanced liver disease," Professor Michael Manns, the study's lead investigator from Hannover Medical School in Germany, said in a statement.

The study results were presented at the annual meeting of the European Association for the Study of the Liver (EASL) in London.

Genotype 1 is the most prevalent and considered the most difficult to treat form of the virus. Genotype 1b tends to be more common in Europe and 1a is more widely seen in the United States.

Several drugmakers, including Gilead Sciences Inc, AbbVie and Merck & Co are developing a new generation of all-oral hepatitis C treatments that do not include interferon or ribavirin, which cause miserable side effects that have led thousands of patients to put off treatment to wait for the highly touted new drugs.

In clinical trials, the new drugs have demonstrated cure rates in excess of 90 percent while cutting treatment duration to 12 weeks with few side effects, leading to Wall Street forecasts of multibillion-dollar annual sales in what is shaping up to be a fiercely competitive market.

Prior to the recent approval of the first of Gilead's new drugs, standard treatments cured about 75 percent of patients and required either 24 or 48 weeks of therapy.

Bristol this week applied for U.S. approval of the two drug combination and said it expects to file for approval of a three-drug combination early next year.

Based on earlier studies, Bristol's three-drug combination is likely to further boost cure rates with 12 weeks of treatment, which would be more competitive to results seen so far from rival drugmakers.

Patients in the Hallmark-Dual trial received 60 mg of daclatasvir once a day and 100 mg of asunaprevir twice daily. The drugs belong to new classes of medicines that work in different ways to prevent the virus from replicating.

The discontinuation rate due to adverse side effects was between 1 and 3 percent, the company said. Headache was the most common side effect, and serious side effects, such as elevations in liver enzymes, were seen in 5 percent to 7 percent of patients.

Liver enzyme elevations were reversible and resolved following treatment, the company said.

About 170 million people are believed to be infected with hepatitis C worldwide. If left untreated the disease can lead to cirrhosis, liver cancer or need for a liver transplant.

(Reporting by Bill Berkrot; Editing by Cynthia Osterman)

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Also See: Bristol-Myers Squibb Presents Phase III Data Demonstrating that Investigational All-oral Daclatasvir and Asunaprevir Therapy Achieved SVR12 Rates of up to 90% Among Broad Range of Genotype 1b Hepatitis C Patients

Bristol-Myers Squibb Presents Phase III Data Demonstrating that Investigational All-oral Daclatasvir and Asunaprevir Therapy Achieved SVR12 Rates of up to 90% Among Broad Range of Genotype 1b Hepatitis C Patients

• Results of the HALLMARK-Dual study include data among genotype 1b cirrhotic and non-cirrhotic, treatment-naïve, non-responder, and peginterferon/ribavirin ineligible and intolerant patients
• Study reinforces the potential of daclatasvir-based regimens to treat HCV patients with high unmet needs
• Data to be presented during late-breaker session at EASL The International Liver Congress^TM

Category: R&D News

Thursday, April 10, 2014 7:00 am EDT

"Daclatasvir has unique scientific characteristics that support ongoing research for its use in multiple all-oral HCV regimens"

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced Phase III results from the global HALLMARK-Dual study investigating the all-oral, interferon- and ribavirin-free regimen of daclatasvir (DCV), a NS5A inhibitor, and asunaprevir (ASV), a NS3 inhibitor, among genotype 1b hepatitis C virus (HCV) infected patients. Results showed that the 24-week regimen achieved an overall sustained virologic response (a functional cure) 12 weeks after the end of treatment (SVR₁₂) among treatment-naïve (90%), peginterferon/ribavirin non-responder (82%), and peginterferon/ribavirin ineligible/intolerant (82%) patients, including cirrhotic and non-cirrhotic patients (84% and 85%). In the study the DCV+ASV regimen was generally well tolerated. These data will be presented this week at the 49th annual meeting of the European Association for the Study of the Liver (EASL) The International Liver Congress^TM in London, April 9-13.

Globally, there are 170 million people infected with HCV, with genotype 1 being the most prevalent. There are 9 million people infected in Europe, where there is a high prevalence of HCV genotype 1b.

“Not only was the daclatasvir and asunaprevir regimen highly effective among study participants, it was also very well tolerated, even among sicker patients with more advanced liver disease and higher unmet needs,” said lead study investigator Professor Michael P. Manns, director of the Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School, Germany. “Despite a rapidly evolving HCV treatment paradigm, physicians and patients remain in need of new all-oral, interferon- and ribavirin-free regimens that have the potential to achieve virologic cure across a broad range of patients, including those with advanced liver disease and cirrhosis.”

These data were part of the company’s recent DCV and ASV new drug application (NDA) submissions to the U.S. Food and Drug Administration (FDA), and helped support the validated marketing authorization application to the European Medicines Agency for the use of DCV in combination with other agents for the treatment of adults with HCV with compensated liver disease, including genotypes 1, 2, 3, and 4. These data are comparable to a similar Phase III study of this regimen in Japanese patients, which led to the submission of a New Drug Application with Japan’s Pharmaceutical and Medical Devices Agency.

“Daclatasvir has unique scientific characteristics that support ongoing research for its use in multiple all-oral HCV regimens,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “In addition to the HALLMARK-Dual study, we are pleased to be presenting data at EASL on our investigational 3DAA fixed-dose-combination, as well as daclatasvir in combination with other HCV compounds.”

Study Design and Results

This Phase III multinational clinical trial involved 116 sites in 18 countries, including countries that have a high prevalence of genotype 1b such as Korea and Taiwan. In the study, treatment-naïve patients (n=205) received DCV 60 mg once daily plus ASV 100 mg twice daily for 12 weeks, and 102 patients received matching placebo for 12 weeks. The DCV+ASV treatment-naïve group continued treatment through week 24; placebo recipients entered another DCV+ASV study. The peginterferon/ribavirin-ineligible/intolerant (n=235) and non-responder patients (n=205) received the same doses of DCV and ASV for 24 weeks. The primary endpoint was the percentage of patients with a sustained virologic response at 12 weeks after the end of treatment (SVR₁₂).

Virologic Response

• 90% of treatment-naïve patients achieved SVR₁₂
• 82% of patients with prior null or partial response to peginterferon/ribavirin (non-responders) achieved SVR₁₂
• 82% of peginterferon/ribavirin ineligible/intolerant patients achieved SVR₁₂
  • Among peginterferon/ribavirin ineligible/intolerant patients, SVR₁₂ was achieved by patients with anemia/neutropenia (91%); depression (80%) and compensated advanced fibrosis/cirrhosis with thrombocytopenia (73%).

Results among Cirrhotic Patients treated with DCV+ASV

• At baseline, 33 treatment-naïve, 63 non-responders, and 111 ineligible/intolerant patients had cirrhosis. Cirrhotic patients made up ~32% of the study population.

• SVR rates were similar in cirrhotic (84%) and non-cirrhotic (85%) patients.

The regimen used in this Phase III study resulted in low rates of discontinuation (1-3%) due to adverse events (AEs). In addition, the rate of serious adverse events (SAEs) was low (5-7%). Headache was the most common AE in the study (24-25%). No deaths occurred, and no clinically meaningful differences were observed in frequencies of SAEs, AEs leading to discontinuation, or grade 3/4 ALT/AST (liver enzymes) elevations in patients with or without cirrhosis. Importantly, all grade 3/4 ALT/AST elevations observed were reversible and resolved off-treatment.

About Hepatitis C

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. Up to 90 percent of those infected with hepatitis C will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, up to 20 percent of people with chronic hepatitis C will develop cirrhosis; of those, up to 25 percent may progress to liver cancer.

About Bristol-Myers Squibb’s HCV Portfolio

Bristol-Myers Squibb’s research efforts are focused on advancing late-stage compounds to deliver the most value to patients with hepatitis C. At the core of our pipeline is daclatasvir (DCV), an investigational NS5A replication complex inhibitor that has been studied in more than 5,500 patients as part of multiple direct-acting antiviral (DAA) based combination therapies. DCV has shown a low drug-drug interaction profile, supporting its potential use in multiple treatment regimens and in people with co-morbidities.

Daclatasvir is being investigated in combination with sofosbuvir in high unmet need patients, such as pre- and post-transplant patients, HIV/HCV co-infected patients, and patients with genotype 3, as part of the ongoing Phase III ALLY Program.

In 2014, the U.S. Food and Drug Administration (FDA) granted Bristol-Myers Squibb’s investigational DCV Dual Regimen Breakthrough Therapy Designation for use as a combination therapy in the treatment of genotype 1b HCV infection.

In 2013, Bristol-Myers Squibb’s investigational all-oral 3DAA Regimen (daclatasvir/ asunaprevir/BMS-791325) also received Breakthrough Therapy Designation, which helped to expedite the start of the ongoing Phase III UNITY Program. Study populations include non-cirrhotic naïve, cirrhotic naïve and previously treated patients. The daclatasvir 3DAA regimen is being studied as a fixed-dose-combination treatment with twice daily dosing.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that clinical trials of these compounds will support regulatory filings, or that DCV or any other compounds mentioned in this release will receive regulatory approval or, if approved, that they will become commercially successful products. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2013 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

EASL The International Liver Congress is a registered trademark of European Association for the Study of the Liver.

Contact:

Bristol-Myers Squibb
Media:
Jeff Smith,
Office: +33(0) 1 58 83 83 21
Cell: +33(0) 6 03 99 40 18
jr.smith.paeurope@bms.com
or
Carrie Fernandez
Office: +1-609-252-4831
Cell: +1-215-859-2605
carrie.fernandez@bms.com
or
Investors:
Ranya Dajani, +1-609-252-5330
ranya.dajani@bms.com
or
Ryan Asay, +1-609-252-5020
ryan.asay@bms.com

Source

Bristol-Myers Squibb Submits NDAs for Daclatasvir and Asunaprevir to US FDA for the Treatment of Hepatitis C

U.S. application submission marks third major daclatasvir regulatory milestone globally, follows E.U. and Japan

Monday, April 7, 2014 8:00 am EDT

PRINCETON, N.J..--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) "These FDA submissions represent a major step towards offering daclatasvir-based regimens to U.S. HCV patients, many of whom continue to have high unmet medical needs"

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) announced today that they have submitted new drug applications (NDAs) with the U.S. Food and Drug Administration (FDA) for the investigational products daclatasvir (DCV), an NS5A replication complex inhibitor, and asunaprevir (ASV), a NS3 protease inhibitor. The data submitted in the NDAs support the use of DCV+ASV in patients with genotype 1b hepatitis C (HCV). The DCV NDA also seeks approval for use of this compound in combination with other agents for multiple genotypes. The submissions are subject to FDA review for acceptance for filing.

“These FDA submissions represent a major step towards offering daclatasvir-based regimens to U.S. HCV patients, many of whom continue to have high unmet medical needs,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “We are excited to have achieved this milestone and, looking forward, will continue to innovate and invest in daclatasvir in a range of patient types and regimens.”

These submissions follow the recent announcement that the FDA granted the investigational DCV Dual Regimen (DCV+ASV) Breakthrough Therapy Designation. In 2013, the investigational all-oral 3DAA Regimen (daclatasvir/asunaprevir/BMS-791325) also received Breakthrough Therapy Designation, and the company anticipates submitting this regimen for FDA review in Q1 2015.

In January 2014, the European Medicines Agency (EMA) validated the company’s marketing authorization application for the use of DCV in combination with other agents for the treatment of adults with HCV with compensated liver disease, including genotypes 1, 2, 3, and 4, and this application is under accelerated review. In addition, NDAs for DCV and ASV are under priority review by Japan’s Pharmaceutical and Medical Devices Agency for patients with chronic HCV genotype 1b, classified as either interferon-ineligible naïve/intolerant or non-responders to interferon and ribavirin.

About Hepatitis C

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. Approximately 170 million people worldwide are infected with hepatitis C, with an estimated 2.7–3.9 million chronically infected in the United States. Up to 90 percent of those infected with hepatitis C will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, up to 20 percent of people with chronic hepatitis C will develop cirrhosis; of those, up to 25 percent may progress to liver cancer.

About Bristol-Myers Squibb’s HCV Portfolio

Bristol-Myers Squibb’s research efforts are focused on advancing late-stage compounds to deliver the most value to patients with hepatitis C. At the core of our pipeline is daclatasvir (DCV), an investigational NS5A replication complex inhibitor that has been studied in more than 5,500 patients as part of multiple direct-acting antiviral (DAA) based combination therapies. DCV has shown a low drug-drug interaction profile, supporting its potential use in multiple treatment regimens and in people with co-morbidities.

DCV is currently being studied in the ongoing Phase III UNITY Program, where it is being investigated as part of an all-oral 3DAA Regimen (daclatasvir/asunaprevir/BMS-791325). Study populations include non-cirrhotic naïve, cirrhotic naïve and previously treated patients. The 3DAA Regimen is being studied as a fixed-dose-combination treatment with twice daily dosing.

Daclatasvir is also being investigated in combination with sofosbuvir in high unmet need patients, such as pre- and post-transplant patients, HIV/HCV co-infected patients, and patients with genotype 3, as part of the ongoing Phase III ALLY Program.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that clinical trials of these compounds will support regulatory filings, or that DCV or any other compounds mentioned in this release will receive regulatory approval or, if approved, that they will become commercially successful products. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2013 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

Contact:

Bristol-Myers Squibb
Media:
Carrie Fernandez,
Office: +1-609-252-4831; Cell: +1-215-859-2605
carrie.fernandez@bms.com
or
Investors:
Ranya Dajani, 609-252-5330, ranya.dajani@bms.com
Ryan Asay, 609-252-5020, ryan.asay@bms.com

Source

New Phase III Data from Once-Daily Simeprevir Presented at the Conference of the Asian Pacific Association for the Study of the Liver (APASL)

Stockholm, Sweden — Medivir AB (OMX: MVIR) today announced that new phase III data for the once-daily protease inhibitor simeprevir have been presented at the Conference of the Asian Pacific Association for the Study of the Liver (APASL) in Brisbane, Australia.

• The phase III ATTAIN study in treatment-experienced adult patients with chronic hepatitis C virus (HCV) and compensated liver disease achieved its primary efficacy endpoint by demonstrating non-inferiority of simeprevir compared to telaprevir when both are given in combination with PegIFN/RBV. Simeprevir demonstrated superior safety profile including fewer adverse events (AEs), fewer serious adverse events (SAEs) and less anemia versus telaprevir.

• Pooled analysis of data from the phase III QUEST-1 and QUEST-2 studies confirmed efficacy in treatment-naïve genotype 1b HCV patients, with 85 percent (ITT analysis) of treatment-naïve patients achieving SVR12 when treated with simeprevir in combination with PegIFN/RBV, compared to 53 percent when treated with placebo in combination with PegIFN/RBV.

• In the PROMISE phase III trial of prior relapse patients, a subgroup analysis of genotype 1b patients demonstrated that 86 percent (ITT analysis) of these patients achieved SVR12 when treated with simeprevir in combination with PegIFN/RBV, compared to 43 percent when treated with placebo in combination with PegIFN/RBV.

“We are very pleased to report on the successfully completed phase III ATTAIN study demonstrating non-inferiority of simeprevir compared with telaprevir, and a superior safety profile in this difficult to treat patient group. Moreover, the further analysis of the genotype 1b HCV patients of the phase III studies QUEST-1, QUEST-2 and PROMISE demonstrated very high SVR12 rates supporting the strength of simeprevir as a treatment option for this large patient population” says Charlotte Edenius, EVP Development, Medivir AB.

ATTAIN
About the ATTAIN study
The multicenter phase III clinical study of treatment-experienced genotype 1 HCV patients partial- and null-responder patients to at least one previous course of PegIFN/RBV therapy called the ATTAIN study is a randomized, double-blind, two-arm study. In the trial, 771 patients were randomized (1:1) to treatment with either 150 mg of simeprevir once daily plus PegIFN/RBV or 750 mg of telaprevir three times per day plus PegIFN/RBV for 12 weeks, followed by 36 weeks of PegIFN/RBV alone.

Results from the ATTAIN study
Results from ATTAIN show that simeprevir achieved its primary endpoint of non-inferiority to telaprevir in treatment-experienced HCV patients and demonstrated a superior safety profile. In the study, 54 percent of chronic HCV genotype 1 prior partial- and null-responder patients treated with simeprevir administered once daily in combination with pegylated interferon and ribavirin achieved the primary endpoint of sustained virologic response 12 weeks after end of treatment (SVR12) compared to 55 percent of patients treated with telaprevir administered three-times daily plus pegylated interferon and ribavirin.

Among prior null-responder patients, 44 percent of patients in the simeprevir arm achieved SVR12 versus 46 percent of patients in the telaprevir arm. Among prior partial-responder patients, 70 percent of patients in the simeprevir arm achieved SVR12 versus 69 percent of patients in the telaprevir arm.

SVR12 rates across patient subgroups were generally similar between the simeprevir and telaprevir arms, including among patients with the HCV genotype 1a Q80K mutation. Twenty-seven percent of patients with the HCV Q80K mutation achieved SVR12 in the simeprevir arm versus 26 percent in the telaprevir arm. The study also found that 60 percent of patients with the IL28B CC genotype, 55 percent of CT patients and 48 percent of TT patients in the simeprevir arm achieved SVR12, versus 67, 57 and 50 percent of patients in the telaprevir arm, respectively.

The most common adverse events during the first 12 weeks of treatment occurred at a consistently lower frequency in the simeprevir treatment arm compared to the telaprevir treatment arm, including pruritus (31 percent versus 43 percent), fatigue (32 percent versus 38 percent), headache (25 percent versus 29 percent), anemia (13 percent versus 37 percent), and nausea (17 percent versus 28 percent). Thirty-four percent and 18 percent of simeprevir-treated patients experienced on-treatment failure and relapse, respectively, compared to 32 percent and 17 percent of telaprevir-treated patients, respectively. Two percent of patients in the simeprevir arm and eight percent of patients in the telaprevir arm discontinued treatment early due to an adverse event. Serious adverse events were reported in two percent of patients in the simeprevir arm and nine percent of patients in the telaprevir arm.

QUEST-1, QUEST-2 and PROMISE
Pooled analyses of the QUEST-1, QUEST-2 and PROMISE studies of simeprevir combination therapy in genotype 1b HCV patients
In a pooled analysis of the QUEST-1 and QUEST-2 studies, 89 percent of treatment-naïve genotype 1b HCV patients treated with simeprevir in combination with pegylated interferon and ribavirin and met the criteria for response guided therapy (94 percent) achieved SVR12 compared to 53 percent of patients treated with placebo in combination with pegylated interferon and ribavirin (ITT-analysis 85 and 53 percent, respectively). In patients typically considered difficult to treat, 71 percent of patients with the IL28B TT genotype and 78 percent with METAVIR F3-F4 scores achieved SVR12 in the simeprevir arm. Two percent of patients in each treatment arm discontinued treatment with simeprevir or placebo early due to an adverse event.

An analysis of the PROMISE study found that 89 percent of prior-relapser genotype 1b HCV patients treated with simeprevir in combination with pegylated interferon and ribavirin and met the criteria for response guided therapy (95 percent) achieved SVR12 compared to 43 percent of patients treated with placebo in combination with pegylated interferon and ribavirin (ITT-analysis 86 and 43 percent, respectively). In patients typically considered difficult to treat, 68 percent of patients with the IL28B TT genotype and 84 percent with METAVIR F3-F4 scores achieved SVR12 in the simeprevir arm. No patients discontinued treatment with either simeprevir or placebo due to adverse events during the entire treatment phase in this analysis of PROMISE.

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR, mobile: +46 708 537 292

Medivir is required under the Securities Markets Act to make the information in this press release public. The information was submitted for publication at 08.30 CET on 17 March 2014.

About Simeprevir
Simeprevir is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB and indicated for the treatment chronic hepatitis C infection in combination with pegylated interferon and ribavirin in HCV genotype 1 infected patients with compensated liver disease, including cirrhosis.

Janssen is responsible for the global clinical development of simeprevir and has exclusive, worldwide marketing rights, except in the Nordic countries. Medivir AB will retain marketing rights for simeprevir in these countries under the marketing authorization held by Janssen-Cilag International NV. The treatment was approved for the treatment of genotype 1 hepatitis C in September 2013 in Japan and in November 2013 in Canada and USA. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C. This application is under review by the EMA.

Simeprevir is also being studied in several interferon-free regimens using selected combinations of direct-acting antiviral agents with different mechanisms of action. To date, more than 3,700 patients have been treated with simeprevir in clinical trials.

About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

For more information about Medivir AB, please visit the Company’s website: www.medivir.com

Source

Achillion Announces Oral Presentations Given at APASL 2014 Detailing Clinical Activity of ACH-3102, Second-Generation NS5A Inhibitor, Against Genotype 1b HCV

100% SVR Demonstrated in Combination With Sovaprevir, NS3/4A Protease Inhibitor, in Late Breaker Oral Presentation

NEW HAVEN, Conn., March 14, 2014 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced that two oral presentations were made at the 23^rd Asian Pacific Association for the Study of the Liver (APASL) Conference 2014 in Brisbane, Australia. Updated Phase 2 clinical trial results evaluating a 150 mg loading dose followed by 50 mg once daily of ACH-3102 in combination with either once daily 200 mg or 400 mg of sovaprevir and twice daily ribavirin showed that 100% of patients achieved SVR12 (n=8) including subjects who had Y93 mutations at baseline. A second oral presentation on ACH-3102 was made at APASL 2014 that discussed clinical virology and the lack of virologic breakthrough that was observed in the novel Phase 2 clinical trial evaluating ACH-3102 with ribavirin for patients with treatment-naïve genotype 1b HCV. Despite the presence of up to six linked mutations identified at baseline in the NS5A protein, ACH-3102, without the co-administration of interferon or a second direct-acting antiviral, was able to suppress viral replication with no virologic breakthrough observed during 12 weeks of treatment.

Dr. David Apelian, M.D., Ph.D., Chief Medical Officer of Achillion, commented, "The safety, tolerability, high barrier to resistance, and clinical activity observed in these two Phase 2 trials continue to support the differentiated profile of ACH-3102, our second-generation NS5A inhibitor. As a potential cornerstone compound in genotype 1b targeted regimens, we are evaluating ACH-3102 in combination with our macrocyclic NS3/4A protease inhibitor, ACH-2684, and look forward to initiating future clinical trials for broader HCV treatment evaluating ACH-3102 in combination with our NS5B nucleotide polymerase inhibitor, ACH-3422, which is poised to enter Phase 1 trials."

Oral Presentation Details
Session: Late Breaker Oral Presentation
Title: SVR4 results for the combination of ACH-3102 and sovaprevir, with ribavirin, in subjects with genotype 1 chronic hepatitis C infection.
Abstract: LB6
Presenter: David Apelian, M.D.
Date: Friday, March 14, 2014

Session: Concurrent Session
Title: ACH-3102 and ribavirin in genotype-1b hepatitis C patients: Confirmation of the high barrier to viral breakthrough in genotype-1b HCV.
Abstract: 437
Presenter: Mingjun Huang, Ph.D.
Date: Friday, March 14, 2014

e-Poster Presentation
Title: A single direct-acting anti-viral agent, ACH-3102, with ribavirin, is able to achieve a robust anti-viral response in subjects with genotype 1b chronic hepatitis C infection.
Authors: A. Muir, R. Brennan, et al.
Abstract: 625

Reprints of the oral presentation slides and poster will be accessible from the Achillion website at http://www.achillion.com.

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's discovery, clinical development, and commercial teams have advanced multiple novel product candidates with proven mechanisms of action into studies and toward the market. Achillion is focused on solutions for the most challenging problems in infectious disease including HCV and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.

Cautionary Note Regarding Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including the following: the potential benefits of ACH-3102 as an agent to treat HCV-infected patients; and our plans to initiate additional clinical trials of ACH-3102 in combination with other compounds. Achillion may use words such as "expect," "anticipate," "project," "intend," "plan," "aim," "believe," "seek," " estimate," "can," and "may" and similar expressions to identify such forward-looking statements. Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: demonstrate in any current and future clinical trials the requisite safety, efficacy and combinability of its drug candidates; advance the preclinical and clinical development of its drug candidates, including ACH-3422, ACH-3102 and ACH-2684, under the timelines it projects in current and future clinical trials; satisfactorily respond to the clinical hold placed on sovaprevir by the FDA; obtain and maintain necessary regulatory approvals; obtain and maintain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; manage litigation; raise the substantial additional capital needed to achieve its business objectives; and successfully execute on its business strategies. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Quarterly Report on Form 10-K for the year ended December 31, 2013, filed on March 7, 2014, and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any duty to update any forward-looking statement, except as required by applicable law.

Source

Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection

Hepatology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Viral Hepatitis

Hiromitsu Kumada MD¹, Yoshiyuki Suzuki MD¹, Kenji Ikeda MD¹, Joji Toyota MD², Yoshiyasu Karino MD², Kazuaki Chayama MD³, Yoshiiku Kawakami MD³, Akio Ido MD⁴, Kazuhide Yamamoto MD⁵, Koichi Takaguchi MD⁶, Namiki Izumi MD⁷, Kazuhiko Koike MD⁸, Tetsuo Takehara MD⁹, Norifumi Kawada MD¹⁰, Michio Sata MD¹¹, Hidetaka Miyagoshi¹², Timothy Eley PhD¹³, Fiona McPhee PhD¹³, Andrew Damokosh PhD¹³, Hiroki Ishikawa¹², Eric Hughes MD^13,*

DOI: 10.1002/hep.27113

Copyright © 2014 American Association for the Study of Liver Diseasews

Publication History
Accepted manuscript online: 6 MAR 2014 06:10AM EST
Manuscript Accepted: 28 FEB 2014
Manuscript Revised: 21 FEB 2014
Manuscript Received: 10 FEB 2014

Keywords: Direct-acting antiviral; nonresponder; interferon-ineligible; interferon-intolerant; all-oral

Abstract

All-oral combinations of direct-acting antivirals may improve efficacy and safety outcomes for patients with hepatitis C virus (HCV) infection, particularly those who are poor candidates for current interferon/ribavirin-based regimens. In this open-label, phase 3 study, 135 interferon-ineligible/intolerant and 87 nonresponder patients with chronic HCV genotype 1b infection were enrolled at 24 centers in Japan. Patients received daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily for 24 weeks. The primary end point was sustained virologic response 24 weeks after treatment (SVR₂₄). This study is registered with ClinicalTrials.gov (NCT01497834). SVR₂₄ was achieved by 87.4% of interferon-ineligible/intolerant patients and 80.5% of nonresponder (null and partial) patients; rates were similar in cirrhotic (90.9%) and non-cirrhotic (84.0%) patients, and in patients with IL28B CC (84.5%) or non-CC (84.8%) genotypes. Fourteen patients in each group (12.6%) discontinued dual therapy, mainly due to adverse events or lack of efficacy. Nine nonresponder patients received additional treatment with peginterferon/ribavirin per protocol-defined criteria. The rate of serious adverse events was low (5.9%) and varied among patients. The most common adverse events were nasopharyngitis, increased ALT and AST, headache, diarrhea, and pyrexia.

Conclusion: Interferon-free, ribavirin-free all oral therapy with daclatasvir and asunaprevir for 24 weeks is well tolerated and can achieve a high rate of SVR in patients with HCV genotype 1b who were ineligible, intolerant, or had not responded to prior interferon-based therapy. (Hepatology 2014;)

Source

SVR12 results from a phase IIa study evaluating Simeprevir and Daclatasvir in Hepatitis C patients of genotype 1 have been presented at CROI 2014

Stockholm, Sweden — Medivir AB (OMX: MVIR) today announced that study results from a phase IIa trial evaluating simeprevir, a once-daily protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB, in combination with daclatasvir, an investigational once-daily NS5A inhibitor developed by Bristol-Myers Squibb (NYSE: BMY), with and without ribavirin, in patients with hepatitis C (HCV) genotype 1 infection, have been presented at the 21th Conference on Retroviruses and Opportunistic Infections (CROI) on March 4th in Boston, USA. The study was conducted by Bristol-Myers Squibb.

Data from the study demonstrate that sustained virologic response 12 weeks after the end of treatment (SVR12) was reached in 75 to 85 percent of treatment-naïve patients and 65 to 95 percent of prior null responders with HCV genotype 1b after 12 or 24 weeks of treatment.

“We are pleased to report on the successfully completed exploratory phase IIa clinical trial of simeprevir and daclatasvir. The results are promising, but further studies would be required in order to fully assess the potential of the simeprevir/daclatasvir combination.” says Charlotte Edenius, EVP Development, Medivir AB.

Study Design
In this phase IIa open-label study, HCV genotype 1b treatment-naive patients (N=104) and prior null responders (N=43) were randomly assigned (1:1) to receive daclatasvir 30mg QD + simeprevir 150mg QD with or without ribavirin. Two treatment durations were evaluated: patients who completed 12 weeks treatment were re-randomized (1:1) to stop at Week 12 orcontinue treatment through Week 24.

In an exploratory evaluation of HCV genotype 1a patients, treatment naive (N=12) and prior null responder patients (N=9) received daclatasvir + simeprevir + ribavirin for 24 weeks.

Summary – Efficacy
In treatment-naïve HCV genotype 1b patients SVR12 was achieved by 75% (38/51) and 85% (45/53) when treated with simeprevir and daclatasvir, with or without ribavirin, respectively. In HCV genotype 1b prior null responders SVR12 was achieved by 95% (19/20) and 65% (15/23) with or without ribavirin, respectively. Estimated SVR12 rates in HCV genotype 1b patients (adjusted for pre-Week 12 discontinuations) were similar after 12 or 24 weeks of treatment in naive patients but higher after 12 than 24 weeks in prior null responders.

In treatment-naïve HCV genotype 1a patients 67% (8/12) achieved SVR12. All HCV genotype 1a prior null responders were offered pegylated interferon alfa-2a in addition to ribavirin + daclatasvir + simeprevir as rescue therapy due to frequent on-treatment breakthroughs and were counted as treatment failures.

Overall, patients were 92% white, 49% male, 21% cirrhotic, and 76% IL28B non-CC genotype and were well-balanced across treatment groups.

Summary - Safety
The all-oral combination of daclatasvir plus simeprevir, with and without ribavirin, was generally well tolerated. There were two treatment-related serious adverse events (neurotoxicity, liver disorder) and one on-treatment death (unrelated trauma-associated intracranial hematoma). Three patients experienced treatment-related adverse events leading to discontinuation. Seventeen patients experienced grade 3/4 total bilirubin elevations without concurrent transaminase elevations, mostly in patients receiving ribavirin (14/17), consistent with ribavirin-induced hemolysis and known effects of simeprevir on bilirubin transporters.

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR, mobile: +46 708 537 292

Medivir is required under the Securities Markets Act to make the information in this press release public. The information was submitted for publication at 18.15 CET on 4 March 2014.

About Simeprevir
Simeprevir is an NS3/4A protease inhibitor jointly developed by Medivir and Janssen R&D Ireland for the treatment of chronic hepatitis C infection in combination with other antivirals in hepatitis C genotype 1 and 4 infected patients with compensated liver disease, including cirrhosis.

Simeprevir was approved for the treatment of genotype 1 hepatitis C in September 2013 in Japan and in the USA and Canada in November. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 and and genotype 4 chronic hepatitis C. To date, more than 3,700 patients have been treated with simeprevir in clinical trials.

About Daclatasvir
Daclatasvir is an investigational NS5A replication complex inhibitor that has been studied in more than 5,500 patients to date as a foundational agent for multiple direct-acting antiviral-based combination therapies and is currently in phase III development. Daclatasvir has shown antiviral potency and pan-genotypic activity across hepatitis C genotypes in vitro. Daclatasvir has a drug-drug interaction profile that supports its continued study in a variety of hepatitis C combination regimens. Daclatasvir-based regimens are currently under review by regulatory authorities in Japan and Europe.

About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

For more information about Medivir AB, please visit the Company’s website: www.medivir.com

Medivir is a collaborative and agile pharmaceutical company with an R&D focus on infectious diseases and a leading position in hepatitis C. We are passionate and uncompromising in our mission to develop and commercialize innovative pharmaceuticals that improve people’s lives.

Source

Bristol-Myers Squibb Receives U.S. FDA Breakthrough Therapy Designation for All-Oral Daclatasvir Dual Investigational Regimen for Chronic Hepatitis C

• FDA grants Designation request for investigational daclatasvir (DCV) and asunaprevir (ASV) combination therapy for treatment of genotype 1b chronic hepatitis C (HCV) infection
• Marks second Breakthrough Therapy Designation for a daclatasvir-based regimen; 3DAA regimen granted Designation in 2013

Monday, February 24, 2014 8:30 am EST

"The FDA’s decision to grant Breakthrough Therapy Designation for our DCV Dual Regimen (daclatasvir and asunaprevir combination therapy) marks the second time that the FDA has granted the Designation to a daclatasvir-based regimen, further underscoring its potential to help address the high unmet needs of the HCV patient population"

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced that the U.S. Food and Drug Administration (FDA) has granted its investigational DCV Dual Regimen (daclatasvir and asunaprevir) Breakthrough Therapy Designation for use as a combination therapy in the treatment of genotype 1b chronic hepatitis C infection (HCV). The designation is based on data from the company’s ongoing Phase III clinical trial program evaluating the all-oral combination regimen of DCV, an investigational NS5A replication complex inhibitor, and ASV, an investigational NS3 protease inhibitor, without ribavirin.

According to the FDA, Breakthrough Therapy Designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for Breakthrough Therapy Designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.

“The FDA’s decision to grant Breakthrough Therapy Designation for our DCV Dual Regimen (daclatasvir and asunaprevir combination therapy) marks the second time that the FDA has granted the Designation to a daclatasvir-based regimen, further underscoring its potential to help address the high unmet needs of the HCV patient population,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “This is an important milestone for Bristol-Myers Squibb as we continue our strategic focus on the development of innovative medicines to address areas of high unmet medical need, where potential expedited review can make a critical difference for patients.”

Approximately 170 million people worldwide are infected with hepatitis C, with an estimated 2.7–3.9 million chronically infected in the U.S. Many of these people have been living with HCV for decades, putting them at heightened risk for developing serious, potentially life-threatening liver disease.

New data from Bristol-Myers Squibb’s ongoing Phase III clinical program studying the DCV Dual Regimen is anticipated to be presented at an upcoming scientific forum. Data from a separate daclatasvir and asunaprevir Phase III trial in Japanese patients with HCV genotype 1b who were either interferon-ineligible/intolerant or non-responders (null and partial) to interferon-based therapies served as the basis for a regulatory filing in Japan in October 2013.

Bristol-Myers Squibb also recently announced that the European Medicines Agency (EMA) validated the company’s marketing authorization application (MAA) for the use of daclatasvir for the treatment of adults with HCV with compensated liver disease, including genotypes 1, 2, 3, and 4. The application seeks the approval of daclatasvir for use in combination with other agents for the treatment of chronic hepatitis C and will be reviewed under an accelerated regulatory review.

About Hepatitis C

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. Up to 90 percent of those infected with hepatitis C will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, 20 percent of people with chronic hepatitis C will develop cirrhosis and, of those, up to 25 percent may progress to liver cancer.

About Bristol-Myers Squibb’s HCV Portfolio

Bristol-Myers Squibb’s research efforts are focused on advancing late-stage compounds to deliver the most value to patients with hepatitis C. At the core of our pipeline is daclatasvir, an investigational NS5A replication complex inhibitor that has been studied in more than 5,500 patients as a foundational agent for multiple direct-acting antiviral (DAA) based combination therapies.

In 2013, Bristol-Myers Squibb’s investigational all-oral 3DAA Regimen (daclatasvir/ asunaprevir/BMS-791325) received FDA Breakthrough Therapy Designation, which helped to expedite the start of the ongoing Phase III UNITY Program. Study populations include non-cirrhotic treatment naïve and experienced patients, as well as cirrhotic treatment naïve and experienced patients. The daclatasvir 3DAA regimen is being studied as a fixed-dose-combination treatment with twice daily dosing.

In addition, enrollment has begun for the Phase III ALLY Program, in which daclatasvir in combination with sofosbuvir, is being studied in high unmet need patients, such as pre- and post-transplant patients, HIV/HCV co-infected patients and patients infected with HCV genotype 3.

Other compounds in the pipeline include:

• Asunaprevir (ASV) is an investigational NS3 protease inhibitor for hepatitis C which has been studied as a component of DCV-based treatment regimens
• BMS-791325 is a non-nucleoside inhibitor of the NS5B polymerase, currently in Phase III development for hepatitis C as a component of DCV-based treatment regimens
• Peginterferon lambda is an investigational type III interferon that has the potential to offer an alternative to peginterferon alfa in patients for whom an interferon-based regimen is required or preferred

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that DCV or any other compounds mentioned in this release will receive regulatory approval or, if approved, that they will become commercially successful products. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2013, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

Contact:

Bristol-Myers Squibb Company
Media:
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Office: 609-252-4831
Cell: 215-859-2605
carrie.fernandez@bms.com
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Investors:
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ranya.dajani@bms.com
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Ryan Asay, 609-252-5020
ryan.asay@bms.com

Source

Hepatitis C virus genotype 1b increases cumulative lifetime risk of hepatocellular carcinoma

Int J Cancer. 2014 Jan 31. doi: 10.1002/ijc.28753. [Epub ahead of print]

Lee MH, Yang HI, Lu SN, Jen CL, You SL, Wang LY, L'italien G, Chen CJ, Yuan Y; for the REVEAL-HCV Study Group.

Abstract

The association between subtypes of hepatitis C virus (HCV) and risk of hepatocellular carcinoma (HCC) remained inconclusive and evaluated in both case-control and cohort studies. In the case-control study, 397 HCC cases from medical centers were compared with 410 community-based non-HCC controls. All of them were anti-HCV-seropositive, HBsAg-seronegative with serum HCV RNA levels ≥1000 IU/mL. Logistic regression models were utilized to estimate the odds ratio (OR) with 95% confidence interval (95% CI) of HCV subtype after controlling for other HCC risk factors. In the cohort study, 866 anti-HCV-seropositive individuals were followed from 1991 to 2008 to assess the long-term HCC predictability of HCV subtypes. Newly developed HCC cases were ascertained by follow-up health examinations and computerized linkage with national databases. The percentage of HCV 1b subtype was higher among HCC cases than controls (64% vs. 55%, p<0.001). Participant infected with HCV 1b had a higher mean serum HCV RNA level (2.0×10⁶ IU/mL) than those with HCV non-1b (1.2×10⁶ IU/mL, p<0.001). The multivariate-adjusted OR (95% CI) of developing HCC for HCV 1b comparing to non-1b was 1.43 (1.02-2.02). After the long-term follow-up, the cumulative lifetime (30-80 years old) HCC risk was 19.2% and 29.7% for patients infected with HCV non-1b and 1b, respectively (p<0.001). The multivariate-adjusted hazard ratio (95% CI) was 1.85 (1.06-3.22) for HCV 1b compared to non-1b. HCV subtype 1b, the most prevalent subtype in Taiwan, was associated with an increased HCC risk and a proactive clinical management is suggested for patients with HCV 1b. © 2014 Wiley Periodicals, Inc.

Copyright © 2014 UICC.

KEYWORDS: HCV RNA levels, HCV variability, long-term liver progression

PMID: 24482200 [PubMed - as supplied by publisher]

Source

HCV Regimen: No Interferon, No Ribavirin, No Problem

Meeting Coverage

Published: Nov 8, 2013 | Updated: Nov 8, 2013

Coverage of Hepatitis C Virus is supported in part by an independent educational grant from AbbVie Pharmaceuticals.

This report is part of a 12-month Clinical Context series.

By Ed Susman , Contributing Writer, MedPage Today

Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Note that in this uncontrolled trial of patients with HCV, the combination of daclatasvir plus asunaprevir was very effective in inducing virologic response rates.
• Be aware that the trial only enrolled patients who had failed or were ineligible for interferon therapy.

WASHINGTON -- Patients who failed to respond to standard treatment for hepatitis C virus (HCV) infection achieved greater than 80% sustained virologic response at 24 weeks with an all-oral regimen that eschewed both interferon and ribavirin, researchers reported here.

Among 135 patients who were either ineligible for interferon therapy or who were intolerant of the treatment, 87.4% achieved a sustained virologic response -- basically a treatment cure, reported Kazuaki Chayama, MD, PhD, professor of medicine and director of Hiroshima University Hospital.

In his plenary session report at the annual meeting of the American Association for the Study of Liver Diseases, Chayama also reported that 80.5% of 87 previous non-responders or partial responders achieved a sustained virologic response at 24 weeks.

He said that the response at 12 weeks was virtually the same as at 24 weeks: 88.1% of those ineligible or intolerant of interferon-based therapy reached the milestone compared with 80.5% of the non-responders or partial responders achieving a sustained virologic response at 12 weeks.

"Overall, 84.7% of these patients with limited therapeutic options and those patients typically associated with poor responses to other therapies were able to achieve a sustained virologic response," he said.

The 135 patients in the study received daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily. The researchers also enrolled 87 non-responders to previous therapy who received the same treatment regimen.

"Current treatment for chronic hepatitis C virus infection consists of pegylated interferon/ribavirin combined with a direct-acting antiviral," he explained. "In Japan, many patients are excluded from therapy due to the combined effect of an aging Japanese population with chronic hepatitis C virus and the poor tolerability profile with peginterferon/ribavirin-based therapy in this population."

He noted that although telaprevir/peginterferon/ribavirin therapy was approved for both treatment-naïve and treatment-experienced patients, the efficacy in nonresponder patients with hepatitis C virus genotype-1 was insufficient -- about one-third of patients responded.

The two investigative agents attack the virus in different ways. Daclatasvir is a potent NS5A replication complex inhibitor with pan-genotypic antiviral activity. Asunaprevir is a potent NS3 protease inhibitor with antiviral activity against genotypes 1, 4, 5, and 6. Chayama said the phase III study he described follows successful phase II studies showing a strong impact on patients with genotype 1b.

The median age of the 222 participants in the trial was 62.5, about 35% were men, and about 10% were diagnosed with cirrhosis. Baseline factors, including male gender, advanced age, high baseline hepatitis C virus RNA, and cirrhosis, did not appear to have an impact on response rates, Chayama said.

Overall 12.6% of the patients in the study discontinued therapy -- 6.8% due to lack of efficacy and 5% due to adverse events. Chayama said 5.6% of patients experienced serious adverse events. There were no deaths in the study.

Although the study was conducted among a Japanese population, Michael Fried, MD, professor of medicine and director of the University of North Carolina Liver Center in Chapel Hill, told MedPage Today, "These results can be extrapolated to an American or European hepatitis C virus population that had genotype 1 infection."

"It will work in this population but it will be tested in this population as well. These drugs will have to be more broadly studied. As you have seen if we get the right combination of drugs we can get successful results," Fried said.

The Japanese population mainly had genotype 1b infections, he said. Yet the success rate in achieving sustained virologic response was greater than 80%. "When I first started treating hepatitis C virus infection in the 1990s we were getting sustained virologic response rate in the 7% area, and to be getting response in the 80% to 90% levels we are seeing today is phenomenal."

He acknowledged that historically genotype 1 hepatitis C infection has been considered a more difficult disease to treat than genotypes 2 or 3, but in studies presented at The Liver Meeting 2013, "What has emerged is that genotype 3 is the new genotype 1. With these new drugs I think there has been a surprise that we get suboptimal results with genotype 3."

Primary source: American Association for the Study of Liver Diseases
Source reference: Chayama M, et al "All-oral combination of daclatasvir plus asunaprevir in interferon ineligible naive/intolerant and nonresponder Japanese patients chronically infected with HCV genotype 1b: Results from a phase 3 trial" AASLD 2013.

Source

Also See: BMS Submits First All-Oral, Interferon-Free and Ribavirin-Free Treatment Regimen for Regulatory Review in Japan for Patients with Chronic Hepatitis C Infection

All-oral, Combination Therapy for Patients with Hepatitis C Provides High Sustained Virologic Response Rate

Presented: November 5, 2013 -- Walter E. Washington Convention Center, Washington, DC

WASHINGTON, Nov. 4, 2013 /PRNewswire/ -- In this abstract to be presented at the annual meeting of the American Association for the Study of Liver Diseases, researchers from Japan provided 12-week results from their phase III study of an all-oral treatment regimen. In their presentation at The Liver Meeting® they will also provide 24-week results.

The group administered a combined treatment of daclatasvir and andasunaprevir. The treatment did not include peg-interferon/ribavirin. The treatment group were infected with hepatitis C genotype 1b, and they were either ineligible, naive or intolerant to treatment with peginterferon/ribavirin or they were nonresponders to such treatment.

For the 24-week study, 222 patients were studied, and 85.6 percent of those patients had a sustained virologic response (SVR) by week 12. According to Kazuaki Chayama, MD, PhD, "Only around 75 percent of patients treated with peg-interferon /ribavirin/telaprevir had a SVR but that therapy was associated with severe side effects and high cost. New oral-only drug therapy is quite safe and the eradication rate is so high."

Dr. Chayama continues, "These results, which were quite amazing, were expected after conducting the phase II trial, and we are very happy to confirm them in the phase III trial. I think further development of direct acting antivirals (DAAs) such as polymerase inhibitors will improve the SVR even more. Further research is necessary to develop an even higher SVR rate -- possibly 100 percent. Combination therapy with polymerase inhibitors is one way. Combination of these DAAs with peg-interferon (or interferon lambda) with or without ribavirin should be considered for patients with multi-drug resistance."

It was also noted that response rate was independent of baseline factors such as gender, age, baseline HCV RNA, etc. Although no death occurred during the study, 26 patients discontinued treatment due to adverse events or lack of efficacy.

Abstract title:

All-oral Combination of Daclatasvir Plus Asunaprevir in Interferon Ineligible Naive/Intolerant and Nonresponder Japanese Patients Chronically Infected with HCV Genotype 1b: Results from a Phase 3 Trial

AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Washington, November 2-5, will bring together more than 9,000 researchers from 55 countries.

A pressroom will be available from November 1 at the annual meeting. For copies of abstracts and press releases, or to arrange researcher interviews, contact Gregory Bologna at 703-299-9766.

Press releases and all abstracts are available online at www.aasld.org.

Media Contact: Gregory Bologna
703/299-9766   
gbologna@aasld.org
Press Room: November 1 – 5, 2013
Walter E. Washington Convention Center, Washington, DC
Telephone: 202-249-4092

Researcher: Kazuaki Chayama, MD, PhD
Email: chayama@hiroshima-u.ac.jp
Phone: +81-82-257-5190

This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.XpressPress.com.

SOURCE American Association for the Study of Liver Diseases (AASLD)

RELATED LINKS
http://www.aasld.org

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Also See: BMS Submits First All-Oral, Interferon-Free and Ribavirin-Free Treatment Regimen for Regulatory Review in Japan for Patients with Chronic Hepatitis C Infection

New GT-1b Data from ABT-450 Containing Regimen Being Presented at The Liver Meeting

SVR12 Rates of 95% in HCV Treatment Naïve Patients and 90% in Prior Null Responders Reported in PEARL-I Study

WATERTOWN, Mass.--(BUSINESS WIRE)--Nov. 3, 2013-- Enanta Pharmaceuticals, Inc., (NASDAQ: ENTA) a research and development-focused biotechnology company dedicated to creating small molecule drugs in the infectious disease field, today announced that additional data from AbbVie’s M13-393 study, referred to as PEARL-I, will be presented in an oral presentation at 5:15 p.m. ET today at The Liver Meeting, the 64^th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, D.C.

In PEARL-I, SVR12 rates of 95% (40/42) in hepatitis C (HCV) GT-1b treatment-naïve patients and 90% (36/40) among prior null responders will be presented in this intent-to-treat analysis. Two patients in the treatment-naive arm did not achieve SVR12 due to loss to follow up. In the null responder arm, one patient experienced breakthrough and three patients relapsed.

PEARL-I is a phase-2b, interferon-free, 320 patient study being conducted by AbbVie to evaluate the once-daily, two-DAA regimen consisting of ABT-450/r (protease inhibitor plus ritonavir) + ABT-267 (AbbVie’s NS5A inhibitor) in HCV treatment-naïve patients and treatment-experience patients. GT-1b treatment arms are ribavirin-free and also include cirrhotic patients while GT-4 arms explore treatment with and without ribavirin.

“We are very encouraged by the strong SVR12 rates from this simplified 2-DAA, once-daily regimen that includes our lead HCV protease inhibitor, ABT-450,” commented Jay R. Luly, Ph.D., President and Chief Executive Officer. “We look forward to data from Phase 3 studies of three-DAA regimens containing ABT-450 being reported in the coming months.”

Protease Inhibitor Collaboration with AbbVie (formerly the research-based pharmaceutical business of Abbott Laboratories)

In December 2006, Enanta and Abbott announced a worldwide agreement to collaborate on the discovery, development and commercialization of HCV NS3 and NS3/4A protease inhibitors and HCV protease inhibitor-containing drug combinations. ABT-450 is a protease inhibitor identified as a lead compound through the collaboration. Under the agreement, AbbVie is responsible for all development and commercialization activities for ABT-450. Enanta received $57 million in connection with signing the collaboration agreement, has received $55 million in subsequent clinical milestone payments, and is eligible to receive an additional $195 million in payments for regulatory milestones, as well as double-digit royalties worldwide on any revenue allocable to the collaboration’s protease inhibitors. Also, for any additional collaborative HCV protease inhibitor product candidate developed under the agreement, Enanta holds an option to modify the U.S. portion of it rights to receive milestone payments and worldwide royalties. With this option, Enanta can fund 40 percent of U.S. development costs and U.S. commercialization efforts (sales and promotion costs) for the additional protease inhibitor in exchange for 40 percent of any U.S. profits ultimately achieved after regulatory approval instead of receiving payments for U.S. commercial regulatory approval milestones and royalties on U.S. sales of that protease inhibitor.

About Enanta

Enanta Pharmaceuticals is a research and development-focused biotechnology company that uses its robust chemistry-driven approach and drug discovery capabilities to create small molecule drugs in the infectious disease field. Enanta is discovering and developing novel inhibitors designed for use against the hepatitis C virus (HCV). These inhibitors include members of the direct acting antiviral (DAA) inhibitor classes – protease (partnered with AbbVie), NS5A (partnered with Novartis) and nucleotide polymerase – as well as a host-targeted antiviral (HTA) inhibitor class targeted against cyclophilin. Additionally, Enanta has created a new class of antibiotics, called Bicyclolides, for the treatment of multi-drug resistant bacteria, with a focus on developing an intravenous and oral treatment for hospital and community MRSA (methicillin-resistant Staphylococcus aureus) infections.

Forward Looking Statements Disclaimer

This press release contains forward-looking statements, including with respect to clinical data, plans for announcing additional data, and the planned clinical development of ABT-450. Statements that are not historical facts are based on our management’s current expectations, estimates, forecasts and projections about our business and the industry in which we operate and our management’s beliefs and assumptions. The statements contained in this release are not guarantees of future performance and involve certain risks, uncertainties and assumptions, which are difficult to predict. Therefore, actual outcomes and results may differ materially from what is expressed in such forward-looking statements. Important factors that may affect actual results include final results of ongoing clinical trials, the development and marketing efforts of AbbVie (our collaborator on ABT-450), regulatory actions affecting clinical development of ABT-450 and clinical development of competitive product candidates. Enanta cautions investors not to place undue reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this release, and Enanta undertakes no obligation to update or revise these statements, except as may be required by law.

Source: Enanta Pharmaceuticals, Inc.

Investor Contact
Enanta Pharmaceuticals, Inc.
Carol Miceli, 617-607-0710
cmiceli@enanta.com
or
Media Contact
MacDougall Biomedical Communications
Kari Watson, 781-235-3060
kwatson@macbiocom.com

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Optimization of an Interferon-free Hepatitis C Virus Treatment Regimen Containing the NS3/4A Protease Inhibitor Faldaprevir, the Non-nucleoside NS5B Inhibitor BI207127, and Ribavirin for Genotype 1b-infected Patients

Infectious Disease Week (IDWeek)
October 2-6, 2013
San Francisco, Ca

715. Optimization of an Interferon-free Hepatitis C Virus Treatment Regimen Containing the NS3/4A Protease Inhibitor Faldaprevir, the Non-nucleoside NS5B Inhibitor BI207127, and Ribavirin for Genotype 1b-infected Patients

Session: Poster Abstract Session: Antimicrobials: Novel Agents

Friday, October 4, 2013

Room: The Moscone Center: Poster Hall C

Posters 715_IFNFree_faldaprevir_deleobuvir.pdf (109.5 kB)

Background: SOUND-C1 demonstrated the potent antiviral activity of faldaprevir (FDV) and BI207127 + ribavirin (RBV) without interferon (IFN) in HCV GT1-infected patients. SOUND-C2 investigated the safety, efficacy, and treatment duration of FDV 120mg QD, BI207127 600mg BID or TID (with an additional induction dose of 1200mg at first intake) ± RBV for 16, 28, or 40 weeks in 362 HCV GT1-infected patients. Dose and treatment duration were optimized in SOUND-C3. Notably, recently completed pivotal phase 3 trials of FDV + PegIFN + RBV (STARTVerso™) have yielded promising results across both GT-1a and 1b patients, including patients with compensated cirrhosis.

Methods: Pharmacokinetic and pharmacodynamic analysis in SOUND-C2 indicated an interaction between FDV and BI207127 that increased plasma concentrations of each drug. Increased plasma concentrations of BI207127 correlated with gastrointestinal adverse events (AEs) and treatment discontinuation in the TID groups. SOUND-C3 eliminated the induction dose and limited treatment duration to 16 weeks in order to optimize therapy.

In SOUND-C3, GT1a patients (n=12) carrying the IL28b CC genotype (rs12979860, GT1a-CC) and GT1b patients (n=20) carrying any IL28b genotype were treated with FDV 120mg QD + BI207127 600mg BID without induction dose + RBV for only 16 weeks. Both studies included cirrhotic patients (9% in SOUND-C2 and 13% in SOUND-C3) and had a primary endpoint of SVR12.

Results: In SOUND-C2, SVR12 rates differed between GT1a- (up to 47%) and GT1b- (up to 85%) infected patients. The presence of cirrhosis had a minor influence on SVR12 rates. Nausea and vomiting were common AEs, especially in the TID arms, but were mainly mild.

In SOUND-C3, 95% (19/20) of GT1b-infected patients achieved SVR12 with the modified 16-week IFN-free regimen compared with 17% (2/12) of GT1a-CC-infected patients.

Conclusion: Modifying the IFN-free regimen of FDV, BI207127, + RBV in SOUND-C3 resulted in an SVR rate of 95% for GT1b-infected patients compared with 85% in SOUND-C2 after 16 weeks of treatment. GT1a-CC infected patients had a clearly lower SVR12 rate with 16-week therapy. The optimized 16-week IFN-free regimen is being investigated in phase 3 studies in GT1b-infected patients.

Parvez Mantry, MD, Hepatobiliary Tumor Program, The Liver Institute at Methodist Dallas Medical Center, Dallas, TX, Marcus Schuchmann, MD, Klinikum Der Johannes Gutenberg, University Hospital Mainz, Mainz, Germany, Ansgar Lohse, MD, Department of Internal Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Keikawus Arasteh, MD, EPIMED c/o Auguste-Viktoria-Klinikum, Berlin, Germany, Michael Manns, MD, Hannover Medical School, Hannover, Germany, Thomas Berg, MD, Department of Internal Medicine, University Hospital Leipzig, Leipzig, Germany, Stefan Mauss, MD, Zentrum für HIV und Hepatogastroenterologie, Düsseldorf, Germany, Michael Geissler, MD, Klinik Für Onkologie, Gastroenterologie Und Innere Medizin, Esslingen Hospital, Esslingen, Germany, Wulf Bocher, MD, Boehringer Ingelheim, Biberach, Germany and Stefan Zeuzem, MD, Gastroeneterology, Klinikum der Johann-Wolfgang-Goethe-Universität–Med. Klinik I, Frankfurt, Germany

Disclosures:

P. Mantry, Boehringer Ingelehiem: Investigator, Research grant

M. Schuchmann, Boehringer Ingelehiem: Consultant, Editorial Support and Speaker's Bureau, Consulting fee and Speaker honorarium
Norgine: Consultant, Consulting fee
BMS: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Roche: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Gilead: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Merck: Speaker's Bureau, Speaker honorarium
Falk: Speaker's Bureau, Speaker honorarium
MSD: Speaker's Bureau, Speaker honorarium
DFG: Grant Investigator, Grant recipient

A. Lohse, Boehringer Ingelheim: Editorial Support, None

K. Arasteh, Boehringer Ingelehiem: Board Member, Consultant, Grant Investigator and Speaker's Bureau, Consulting fee, Grant recipient and Speaker honorarium

M. Manns, Roche: Consultant, Grant Investigator and Speaker's Bureau, Grant recipient and Speaker honorarium
Gilead: Grant Investigator and Speaker's Bureau, Grant recipient and Speaker honorarium
Novartis: Grant Investigator, Grant recipient
Boehringer Ingelheim: Grant Investigator, Grant recipient
BMS: Grant Investigator and Speaker's Bureau, Grant recipient and Speaker honorarium
Merck: Grant Investigator and Speaker's Bureau, Grant recipient and Speaker honorarium
Janssen: Grant Investigator and Speaker's Bureau, Grant recipient and Speaker honorarium

T. Berg, BMS: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Essex Pharma: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Gilead: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
GSK: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Novartis: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Roche: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Schering-Plough: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Vertex: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium

S. Mauss, Abbott: Grant Investigator, Scientific Advisor and Speaker's Bureau, Research grant, Research support and Speaker honorarium
BMS: Scientific Advisor and Speaker's Bureau, Speaker honorarium
Tibotec: Scientific Advisor and Speaker's Bureau, Speaker honorarium
Roche: Speaker's Bureau, Research support and Speaker honorarium
GSK: Scientific Advisor, Consulting fee
Gilead: Scientific Advisor, Consulting fee

M. Geissler, Boehringer Ingelehiem: Grant Investigator, Research grant

W. Bocher, Boehringer Ingelheim: Employee, Salary

S. Zeuzem, Abbott: Consultant, Consulting fee
Achillion: Consultant, Consulting fee
AstraZeneca: Consultant, Consulting fee
BMS: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Boehringer Ingelheim: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Gilead: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Janssen: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Merck: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Novartis: Consultant, Consulting fee
Roche: Consultant, Consulting fee and Speaker honorarium
Santaris: Consultant, Consulting fee

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Interferon-free treatment for genotype-1b hepatitis C patients: an interview with Professor Wulf Boecher, Boehringer Ingelheim

Published on July 30, 2013 at 6:32 AM

Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)

Please can you give a brief introduction to genotype-1b hepatitis C and how it differs from subtype 1a?

Genotype 1 is, worldwide, the most prevalent genotype of the hepatitis C virus. It accounts for around seventy percent of all hepatitis C infections.

With the introduction of protease inhibitors, it became known that the subtypes 1a and 1b make a difference in terms of treatment response.

Subtypes 1a and 1b are genetically closely related. They share seventy to eighty percent of their genome. However, 1a turned out to be more difficult to treat than 1b, which is easier to treat.

That was also the case with the already approved protease inhibitors, and still is the case with the second generation of protease inhibitors (PIs) like faldaprevir or other second generation PIs that are in late stage development. And it applies for interferon based as well as interferon-free treatments.

Faldaprevir's target in viral polyprotein processing.

*Please note faldaprevir (BI 201335) is an investigational compound and not yet approved. Its safety and efficacy has not yet been fully established.

Source: Boehringer Ingelheim

Do genotypes 1a and 1b affect equal numbers of people, or is one more common than the other?

It is regionally very different. In the US, genotype 1a is more prevalent where it accounts for roughly seventy percent of genotype 1 infections.

In Europe, there is slightly more genotype 1b. So there’s roughly a sixty-forty split, with sixty percent being genotype 1b, forty percent 1a.

If you go further East the prevalence of 1b becomes nearly the only genotype 1. So in Japan, in China, and in large parts of Asia, genotype 1b is basically the vastly prevailing or the only genotype 1 subtype.

Hepatitis C virus travelling in the bloodstream.

Source: Boehringer Ingelheim

Why is eliminating injectable interferon from HCV treatment regimens highly desirable?

I have been working on hepatitis C treatment for many years and it is not only subcutaneous injections that make patients uncomfortable. Interferon really makes patients sick for the whole course of treatment and with current treatments this can be as long as twenty four or forty eight weeks, so nearly one year.

Patients feel like they have the flu, with fever, myalgia, chills, and many other symptoms. Also their neuro-cognitive function is reduced. They have low blood cell count that can lead to infections and to severe bleedings. They suffer from psychiatric side effects like severe depression. There are suicides associated with treatment with interferon.

So interferon is really a trouble-maker for patients; it makes patients sick for the duration of their treatment and it is less effective than the oral treatments that are to come. Treatment lasts longer and there is a high chance patients won’t be cured at the end. In contrast, current triple therapies the next generation triple therapies, as well as the future interferon-free treatments, offer shorter treatment duration and higher cure rates.

Faldaprevir* Protease Inhibitior Mode of Action.

*Please note faldaprevir (BI 201335) is an investigational compound and not yet approved. Its safety and efficacy has not yet been fully established.

Source: Boehringer Ingelheim

How did your interferon-free combination treatment originate and what stage of development is it currently at?

It’s actually based on the knowledge of HIV and tuberculosis treatment; where by combining different oral drugs with a different mode of action it is possible to control or eliminate the virus or mycobacteria.

In HCV, we had two different mode-of-action drugs in late stage development that we combined. We had actually thought we may possibly have a forty-five percent cure rate, which would still have been a very attractive cure rate for patients without any treatment options.

Up to fifty percent of hepatitis c patients right now do not tolerate interferon or have contra-indications against interferon.

But then in our phase two studies we found out that by focusing on the easier-to-treat genotype 1b patients, eighty five to ninety five percent of patients can be cured. This makes this combination very attractive as an alternative to replace interferon-based treatments.

And with this interferon-free treatment, we are currently in phase III development.

Please can you tell us about the recent Phase IIb study into the efficacy and safety of this combination treatment?

This is our second phase IIb trial. Initially (in the SOUND-C2 trial) we tested our interferon-free treatment regimen of faldaprevir, deleobuvir and ribavirin in a large study. We had 362 patients, including patients with liver cirrhosis and all stages of liver disease.

We found that genotype 1a patients are indeed difficult to treat, achieving lower cure rates. That would have been attractive maybe three, four years ago, but not nowadays.

But in this study genotype 1b patients had a cure rate of eighty-five percent.

Then we modified the regimen. We shortened treatment from twenty eight to sixteen weeks in SOUND-C3, which is the study we just published at the Asian Pacific Liver Conference (APASL) in June.

We also dropped a so-called induction dose. So in the old regimen, we had a high dose of our polymerase inhibitor and this was not so well tolerated, as we found out.

So we dropped this, we shortened treatment and we found in genotype 1b patients ninety five percent achieved viral cure. But it turned out that in the more difficult to treat population of genotype 1a patients, only two of seventeen patients were cured. And that confirmed our decision to focus on genotype 1b patients with this regimen.

Progression of liver damage caused by infection with hepatitis C.

Source: Boehringer Ingelheim

What were the results of this study and what do they indicate?

The very high cure rates of ninety five percent confirm our decision to focus on genotype 1b patients with this regimen.

We dropped genotype 1a patients from this regimen. However we are currently investigating a third compound in combination with our interferon free combination with which we strive to address genotype 1a patients.

The tolerability was very good. This was as expected from interferon-free treatment. We saw only minor effects on the red blood cells, which was due to the ribavirin component of the regimen, but we didn’t see any effects on white blood cells or platelets.

We did see mostly mild adverse events like mild rashes or nausea, which were the most common side effects.

Did any patients experience serious adverse events during the trial?

Only two patients had to discontinue treatment for adverse events and only one patient reported a serious adverse event (SAE). So overall, I think we can say that this is very good tolerability.

What serious adverse event did the patient experience?

The SAE patient was a patient who had severe dehydration. He was hospitalized to get some infusions and discontinued HCV treatment early after 6 weeks of treatment. However the condition was managed and resolved and the patient recovered completely from the event but also from his hepatitis C.

What are your plans for the future?

For genotype 1b patients we are in the middle of our phase III evaluations. We are expecting results early next year.

We have three on-going phase III trials:-

• One in treatment-naive genotype 1b patients.
• One in a treatment-naive population that includes interferon ineligible patients, which are patients who have contra indications to interferon based treatments. So these patients have currently no treatment option at all.
• We have a third trial that goes to the highest unmet medical need population, which are patients with decompensated liver cirrhosis.

The first two trials also include patients with compensated liver cirrhosis, but the third trial really addresses the late stage liver cirrhosis, or decompensated liver cirrhosis. These are patients that will die if they do not receive a liver transplant. All studies are on-going as we speak.

Our trials are comprehensively designed and address the real-world patients that physicians see every day in clinical practice. Through robust science, our goal is to provide a safe and highly effective interferon-free treatment for genotype-1b patients.

How do you think the future of genotype-1b hepatitis C treatments will progress?

From a patient and a prescriber or physician’s perspective, the future is very bright.

There are several companies and there will be several regimens available to physicians to pick the best treatment option for a given patient.

There are many factors that need to be considered when prescribing HCV treatments, so there will be no one-size-fits-all approach. In the future individualized treatment will become a reality. Physicians will be able to pick the best treatment option for a given patient depending on:-

• the virus genotype and patient genetics
• on individual patient conditions
• age
• gender
• co-morbidities
• co-medications

Everything will play into this and there will be several interferon-free treatment options that can be really tailored individually to a given patient.

It is exactly our strategy to provide tailored therapy which is optimal for specific patient populations. I think this is where we believe we will excel in.

The treatment landscape will become more complex. In the past, we had only to pick between prescribing pegylated interferon for twenty four, or forty eight weeks, and ribavirin in eight hundred, one thousand or twelve hundred milligrams. This was very easy, no drug-drug interactions.

The future looks like it will be more individualized, with physicians choosing which regimen to provide based on the individual patient’s profile. But this is in fact a luxury situation and a great opportunity.

Where can readers find more information?

Readers can find more information on Boehringer Ingelheim at: http://www.boehringer-ingelheim.com/

Readers can also find more information on HCV at: http://www.newshome.com/

About Professor Wulf Boecher

Wulf trained and worked more than 15 years at Mainz University Hospital in Germany as a Gastroenterologist/ Hepatologist and Infectious Diseases Specialist, where he lectures as an Associate Professor for Internal Medicine.

His main scientific focus has been immune pathogenesis and new treatments of HBV, HCV and HIV infection.

Wulf joined Boehringer Ingelheim for the clinical development of new HCV treatments in 2007 and currently holds the position of Associate Therapeutic Area Head Virology.

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