Video: Conversations from CROI 2014: Dr. Doug Dieterich

 

Uploaded on Mar 11, 2014

At the 2014 Conference on Retroviruses and Opportunistic Infections (CROI), Dr. Ron Valdiserri sat down for an in-depth conversation with Dr. Doug Deiterich of the Icahn School of Medicine at Mount Sinai Hospital in New York, who made several presentations and was involved in scientific posters shared during the conference on hepatitis C mono-infection and HIV/HCV co-infection. Dr. Valdiserri and Dr. Dieterich discussed important advances in the diagnosis and treatment of hepatitis C that received a lot of attention at the conference.

Their conversation includes messages for primary care providers and others in the healthcare field, as well as messages for individuals at risk for or living with hepatitis C virus (HCV) infection.

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CROI 2014: Hepatitis C Treatment in the Real World [VIDEO]

Provided by HIVandHepatitis.com

Published on Monday, 03 March 2014 00:00

Written by Gregory Fowler

The opening day of the 21st Conference on Rtroviruses and Opportuistic Infections (CROI 2014) featured a press conference on advances in the treatment of hepatitis C, with a focus on how new drugs may be used in the real world, given barriers such as high cost and a shortage of experienced medical providers.

The panel of hepatitis C experts included Douglas Dieterich from Mt. Sinai's Ichan School of Medicine, Trevor Hawkins from the Southwest CARE Center, Anita Kohli from the National Institutes of Health, Daniel Cohen from AbbVie, and Marion Peters form the University of California at San Francisco.

The advent of direct-acting agents (DAAs) has ushered in a new era of hepatitis C treatment. Researchers summarized new data on Gilead Sciences' ledipasvir and sofosbuvir (Sovaldi) -- which Dieterich said has been "flying off the shelves" since its December approval -- Janssen's recently approved simeprevir (Olysio), Boehringer Ingelheim's faldaprevir, Bristol-Myers Squibb's daclatasvir-based oral regimen, and AbbVie's 3-drug oral DAA regimen.

[Hepatitis C press conference at CROI 2014, March 3, 2014]

3/4/14

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Opening press conference. 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014). Boston. March 3, 2014.

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Promising Treatments Herald New Era in Hepatitis C Treatment

Provided by BioNews Texas

Posted by: Irlanda J. Espinosa March 10, 2014

Recently, several studies presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, have highlighted promising treatments for serious liver disease, with particular attention being paid to chronic infection caused by the liver-damaging Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection.

For patients who are chronically infected by HCV and HIV simultaneously, there is a substantial increase in the risk of cirrhosis and liver decompression than from being solely infected by HCV. Several companies, such as Boehringer Ingelheim, have been developing oral treatment regimens with durations that are 12 weeks or shorter with lower or absent side-effects for patients with both diseases.

Merck & Co has developed a combination of oral drugs that are highly effective in treating HCV and HIV co-infected patients.  The available data of the ongoing clinical trials for some treatment regimens were presented this Wednesday at CROI, while it is expected more data will be released at the European medical meeting in April.

The regimen consists of the experimental Merck drugs, MK-5172 and MK-8742 (new classes of anti-viral medicines), both with and without ribavirin, in co-infected patients over a 12-week period.

At the end of the period, all 29 patients using the two Merck drugs plus ribavirin presented undetectable levels of HCV (considering this way those patients are cured). On the other hand, 90% of the patients who were under the Merck drugs without ribavirin appeared to have the HCV eliminated from their systems after the 12-week period.

Even when the most common side effects of the treatment were fatigue and headache, no patient discontinued treatment due to side-effects or medication intolerance.

Of course, in a model for addressing HCV infection or co-infection with HIV, the development of new treatments that have the potential to cure effectively 90% of patients with common strains of the virus in a short period of time, is just part of solving the problem. It is necessary to find a way to make these treatments accessible as well..

Source

CROI 2014: HCV Abstract and Poster Presentation Coverage by Jules Levin (NATAP) – Updated March 26, 2014

21st Conference on Retroviruses and
Opportunistic Infections
Boston MA
March 3 - 6, 2014

Reported by Jules Levin

(All links open into new windows)

• The CORE HCV Cascade a Decade Later: Looking Ahead to an IFN-free Era - (03/24/14)
• High Hepatitis C Infection Rate in Birth Cohort Testing of an Urban, Primary Care Clinic Population: HCV Cascade, 8.2% Prevalence - (03/24/14)
• Impact of Rapid Hepatitis C testing on Receipt of Hepatitis C Results in a Public STD Clinic - (03/24/14)
• The burden of hepatitis C infection in Pennsylvania state prisons and implications for treatment - (03/24/14)
• Hepatitis C Virus Incidence in the Amsterdam Cohort Study among Men who have Sex with Men; 1984-2011 - (03/24/14)
• The Treatment Cascade for People with Chronic Hepatitis C Virus Infection in the United States - (03/24/14)
• Implementation of a Hepatitis C testing program in a network of Federally Qualified Health Centers: initial results of an Academic-Community partnership - (03/24/14)
• The Hepatitis C Cascade of Care Among HIV Infected Patients Following Diagnosis of HCV Infection - (03/24/14)
• CROI 2014 March 3 - Martin Delaney Panel: Hepatitis C Virus: From Trials and Tribulation to Triumph - (03/24/14)
• Safety and Efficacy of IFN-free, Sofosbuvir/RBV Therapy in HIV/HCV Liver Transplanted Patients - (03/24/14)
• Safety and Efficacy of IFN-free, Sofosbuvir/RBV Therapy in HIV/HCV Liver Transplanted Patients - (03/24/14)
• Liver-related death among HIV/HCV coinfected individuals, implications for the era of directly acting antivirals - (03/24/14)
• Level of Alcohol Use and Advanced Hepatic Fibrosis in HIV-Infected and Uninfected Patients...."there may be no safe level of alcohol use among HIV+ & HCV+" - (03/24/14)
• Pill Burden and Treatment Duration Reduce Adherence to IFN-Free Hepatitis C Therapy in an Urban Cohort - (03/24/14)
• Telaprevir in Treatment-Experienced HIV-HCV G1 Coinfected Patients (ANRS HC26 TelapreVIH) - (03/24/14)
• Boceprevir for Previously Treated HCV-HIV Coinfected Patients: The ANRS-HC27 BocepreVIH Trial - (03/24/14)
• Boceprevir/Telaprevir-Based Therapy in HIV-Infection: Interim Analysis of a Multicenter Cohort - (03/24/14)
• Telaprevir Increases Ribavirin Toxicity Through eGFR Decrease in HIV-HCV Coinfected Patients - (03/24/14)
• PHARMACOKINETICS OF FALDAPREVIR AND ANTIRETROVIRALS IN PATIENTS WITH HIV/HCV CO-INFECTION - (03/21/14)
• EFFECT OF FALDAPREVIR ON ATAZANAVIR PHARMACOKINETICS IN PATIENTS WITH HIV/HCV CO-INFECTION - (03/21/14)
• EFFECT OF FALDAPREVIR ON RALTEGRAVIR PHARMACOKINETICS IN HEALTHY VOLUNTEERS - (03/21/14)
• FIB-4 Alone Proves Best Predictor of ESLD in People With HCV/HIV - written Mark Mascolini - (03/21/14)
• Post-SVR Liver Decompensation Rate Similar With HCV/HIV and HCV Alone - written Mark Mascolini - (03/21/14)
• Post-Transplant Survival Lower With HIV and HCV-1 Than With HCV-1 Alone - written by Mark Mascolini - (03/12/14)
• Abbvie IFN-free 3 DAA Regimen in HCV Genotype 1-infected Pati ents on Methadone or Buprenorphine - (03/06/14)
• On-treatment Viral Response to MK-5172/MK-8742 ± RBV for 12 Weeks in HCV/HIV Co-infected Patients: The C-WORTHY Study - (03/06/14)
• ABT-493, a Potent HCV NS3/4A Protease Inhibitor With Broad Genotype Coverage - (03/05/14)
• ABT-530, an HCV NS5A Inhibitor With Potent Pangenotypic Activity and High Genetic Barrier to Resistance - (03/05/14)
• All-Oral Combination of Daclatasvir, Asunaprevir, and BMS-791325 for HCV Genotype 1 Infection - (03/04/14)
• Daclatasvir in Combination With Simeprevir With or Without Ribavirin for Hepatitis C Virus Genotype 1 Infection - (03/04/14)
• All-Oral Therapy With Sofosbuvir Plus Ribavirin For the Treatment of HCV Genotype 1, 2, and 3 Infection in Patients Co-infected With HIV (PHOTON-1) - (03/04/14)
• Three-DAA Regimen (Abbvie) Achieves 99% SVR12 Rates in HCV Genotype 1b Naives - written by Mark Mascolini - (03/04/14)
• Simeprevir Plus PegIFN/RBV Yields 74% SVR12 in HCV/HIV Patients - written by Mark Mascolini - (03/04/14)
• SVR12 72% With Faldaprevir Plus PegIFN/RBV in Naives With HCV/HIV - written by Mark Mascolini - (03/04/14)
• Combination Oral, Hepatitis C Antiviral Therapy for 6 or 12 Weeks: Results of the SYNERGY Trial - (03/04/14)
• Simeprevir plus PegIFN/ribavirin in HCV genotype-1/HIV-1 co-infection (Study C212) - (03/04/14)
• Double or Triple DAA Therapy for HCV-1 Yields 95-100% SVRs in 6 or 12 Weeks (SYNERGY Study) - written by Mark Mascolini - (03/04/14)
• PEARL III: SVR ≥99% AFTER 12 WKS OF ABT-450/R/267 + ABT-333 ± RBV IN TREATMENT-NAIVE HCV GT1B INFECTION - (03/04/14)

Source NATAP

Shorter Treatment Strategy Beats Hepatitis C

Published: Mar 6, 2014
By Ed Susman , Contributing Writer, MedPage Today

BOSTON -- A 6-week treatment regimen appeared to be as effective as the more standard 12 weeks of therapy for patients with hepatitis C virus infection, researchers reported here at the annual Conference on Retroviruses and Opportunistic Infections.

In a pilot study that treated 20 patients in each of three arms, all patients treated with the combination of sofosbuvir (Sovaldi, nucleotide NS5B inhibitor) 400 mg with ledipasvir (NS5A inhibitor) 90 mg once daily for 12 weeks achieved a sustained virologic response at 12 weeks' post-treatment (SVR12), reported Anita Kohli, MD, an infectious disease fellow at the National Institutes of Health Clinical Center in Bethesda, Md.

But she also noted that two regimens using the same backbone and adding either the investigative agent GS-9669 (non-nucleoside NS5B inhibitor) 500 mg once daily or GS-9451 (a protease/NS3/4 inhibitor) 80 mg once daily for 6 weeks had similar outcomes: 95% of patients on GS-9669 achieving an SVR12, and 100% of patients on GS-9451 achieving an SVR12.

The one patient in the study who failed to achieve an SVR12 relapsed before SVR4; that individual had stage 3 liver disease, a high viral load, and unfavorable genotype, Kohli said.

All patients in all 3 arms were naive to treatment for hepatitis C virus. All patients were included in the 12-week arm, but patients diagnosed with cirrhosis were excluded from the 6-week trials.

"These results are not statistically significantly different from each other," Kohli told MedPage Today at a press briefing sponsored by the conference organizers.

"We find these results very promising. This was a pilot study," Kohli said. "We will follow these patients out to 48 weeks to see if the results are maintained."

A cure in the context of HCV is a sustained virologic response -- defined as undetectable viral RNA at some prespecified point after ending therapy, usually 12 or 24 weeks.

"What we have learned from this trial is that we can treat patients for shorter durations of therapy and we see that 6 weeks is effective," Kohli said.

"Secondly, these regimens are very simple -- 1, 2, or 3 pills a day. Third, our patient population is one that is historically very difficult to treat -- more than 80% of the patients were African American, most had genotype 1a, most had high viral loads, 25% to 30% of the patients had advanced-stage liver disease.

"The reason we wanted to look at the short-duration therapies is because we think it is very important in treatment of hepatitis C globally in limited resource settings. We really need very simple treatments for the 150 million to 180 million people globally," she said.

All the treatment regimens avoided the use of interferon, once the mainstay of treatment of hepatitis C virus, but a therapy that is difficult to tolerate for many patients. The use of interferon-free directly acting antiviral agents is an emerging approach to improve the efficacy and tolerability of therapy for hepatitis C virus, Kohli said.

However, she noted that the efficacy of interferon and ribavirin-free regimens shorter than 8 to 12 weeks has not been reported. One study evaluating sofosbuvir, ledipasvir, and ribavirin for 6 weeks showed an SVR12 rate of only 68%, she said. She also noted that the optimal combination of directly acting antiviral agents not been established.

Press conference moderator Jean-Michel Pawlotsky, MD, PhD, professor of medicine at Hopital Henri Mondor Creteil/University of Paris-Est, told MedPage Today that, while the results of the SYNERGY trial look interesting, they are not ready for routine implementation.

"There are very small numbers in this study," he said. "We have to see how this will apply to real-life patients. The danger is always to undertreat patients. If the time is too short and it works in a trial and you start treating real-life patients you can have failures. So we really need to extend this trial. It is interesting because it shows that some people can be cured in a very short duration of treatment."

Pawlotsky said he would not be comfortable treating his patients in this manner without more extensive studies.

Ledipasvir is not currently approved in the U.S. Its manufacturer, Gilead, filed last month for FDA approval of the drug in a fixed-dose combination with sofosbuvir.

The study was funded by the National Institutes of Health.

Kohli disclosed no relevant relationships with industry.

Pawlotsky disclosed no relevant relationships with industry.

Primary source: Conference on Retroviruses and Opportunistic Infections
Source reference: Kohli A, et al "Combination oral, hepatitis C antiviral therapy for 6 or 12 weeks: Final results of the SYNERGY trial" CROI 2014; Abstract 27LB.

Source

Faldaprevir NDA has been accepted for review by U.S. FDA as part of a combination regimen for patients with chronic hepatitis C

March 06, 2014

Boehringer Ingelheim Announces Phase 3 SVR12 Results in HCV/HIV Co-Infected Patients Treated with Faldaprevir

Additional drug-drug interaction data for faldaprevir combined with commonly prescribed HIV medications also presented at CROI 2014
Faldaprevir NDA has been accepted for review by U.S. FDA as part of a combination regimen for patients with chronic hepatitis C

For U.S. Media Only

Ingelheim, Germany and Ridgefield, CT, March 6, 2014 – Today Boehringer Ingelheim announced results from STARTVerso^®4 in patients with HCV/HIV co-infection. Hepatitis C viral cure 12 weeks after the conclusion of treatment (SVR12) was achieved by 72% of all patients in the trial. Patients were enrolled in either 120mg or 240mg faldaprevir dose groups. Further, 80% of all patients were eligible for randomization to a shortened duration of treatment (24 versus 48 weeks) because they achieved protocol-defined early treatment success (ETS)* and 86% of these patients achieved SVR12. STARTVerso^®4 is a Phase 3 trial that enrolled 308 hepatitis C (HCV) treatment-naïve or experienced patients with HCV/HIV co-infection and evaluated the efficacy and safety of the investigational compound faldaprevir in combination with pegylated interferon and ribavirin (PegIFN/RBV).

“The SVR12 data from STARTVerso^®4 are encouraging, especially given the inclusion of patients with cirrhosis,” said Peter Piliero, MD, vice president, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “Comprehensive data from our STARTVerso^® clinical trial program, including data from patients with HCV/HIV co-infection, have been filed with the FDA as part of our New Drug Application for faldaprevir.”

In each faldaprevir dose group, 71% (120mg) and 72% (240mg) of patients achieved SVR12. SVR12 results were consistent across patients regardless of HCV genotype-1 subtype (GT1a or GT1b), presence of compensated cirrhosis, dose and duration of faldaprevir, and duration of PegIFN/RBV. In a post hoc analysis, 75% of patients with the Q80K variant achieved SVR12 compared with 71% of patients who did not have the variant.

Serious adverse events (AEs) were reported in 32 patients (10%). To date, 24 patients have prematurely discontinued faldaprevir due to AEs. The most frequent AEs in STARTVerso^®4 were nausea (37%), fatigue (34%), diarrhea (27%), headache (25%) and weakness (23%). Patients will be followed to 24 weeks after the conclusion of treatment (SVR24).

In separate poster presentations at CROI, investigators described the results from analyses that evaluated drug-drug interactions of faldaprevir with common HIV medications, including: efavirenz, atazanavir/ritonavir, darunavir/ritonavir, raltegravir and tenofovir. In each of these analyses, there was no clinically relevant effect of faldaprevir on the pharmacokinetics of any of the HIV medications studied. Patients in STARTVerso^®4 already taking ritonavir-boosted HIV protease inhibitors (darunavir or atazanavir) or efavirenz were enrolled into the 120mg and 240mg faldaprevir groups, respectively.

Boehringer Ingelheim HCV Development Update
The New Drug Application (NDA) for faldaprevir has been accepted for filing by the U.S. Food and Drug Administration (FDA). Faldaprevir is currently under review as a component of a combination antiviral treatment regimen for the treatment of chronic HCV infection in adult patients who are treatment-naïve or have been previously treated with interferon-based treatment, as well as those with compensated liver disease, cirrhosis, or HCV/HIV co-infection. The FDA target action date for faldaprevir is in the fourth quarter of 2014.

The NDA submission for faldaprevir is supported by Boehringer Ingelheim’s STARTVerso^® (NCT01343888, NCT01297270, NCT01358864, NCT01399619) clinical trial program, a multi-study Phase 3 trial program that evaluated faldaprevir for 12 or 24 weeks in combination with pegylated interferon and ribavirin (PegIFN/RBV). The four trials that make up this program studied treatment-naïve, treatment-experienced, and HCV/HIV co-infected patients with chronic genotype-1 (GT1) HCV. The primary efficacy endpoint of each STARTVerso^® trial is viral cure 12 weeks after the conclusion of treatment (SVR12).

In November 2013, Boehringer Ingelheim announced that the faldaprevir application for marketing authorization is under review by the European Medicines Agency (EMA). If authorized by the European Commission, faldaprevir could be available for marketing in the EU in the second half of 2014.

Following an assessment of the blinded Phase 3 trial data from HCVerso^® 1 and 2 for the combination of deleobuvir, faldaprevir and ribavirin, Boehringer Ingelheim has decided to halt further development of deleobuvir-containing HCV regimens. Ongoing regulatory reviews of faldaprevir are not affected by the decision on the deleobuvir-containing regimens.

About Faldaprevir
Faldaprevir is an investigational, oral protease inhibitor that is specifically designed to target viral replication in the liver. Faldaprevir is an investigational compound that has not been approved by the FDA; its safety and efficacy have not been established.

About Boehringer Ingelheim in Hepatitis C Virus (HCV)
In partnership with the scientific community, our clinical trial program is rigorously designed to find answers to the challenges that HCV patients face, including those who are the most difficult to cure. Our pivotal HCV clinical trials for faldaprevir, STARTVerso^®, included four trials that studied treatment-naïve, treatment-experienced, and HCV/HIV co-infected patients with chronic GT1 HCV.

Hepatitis C is a blood-borne infectious disease and a leading cause of chronic liver disease, transplant and failure that affects as many as 150 million people globally. In the United States, approximately 3.2-5.2 million people have chronic HCV infection. Since 1999 there has been a significant increase in deaths due to chronic HCV, which accounts for 15,000 deaths in the United States per year.

STARTVerso^® is a registered service mark of Boehringer Ingelheim International GmbH.

About Boehringer Ingelheim
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

Social responsibility is a central element of Boehringer Ingelheim’s culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

For more information please visit www.us.boehringer-ingelheim.com.
*ETS = protocol-defined early treatment success (week 4 below limit of quantification [BLQ] and week 8 below limit of detection [BLD]).

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Merck’s Investigational Hepatitis C Treatment Regimen MK-5172/MK-8742 Shows Robust Anti-HCV Activity in HIV/HCV Co-Infected Patients with HCV Genotype 1 Infection

Wednesday, March 5, 2014 4:15 pm EST

BOSTON--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced new data from HIV/HCV co-infected patients in the ongoing C-WORTHY Study, a Phase 2 clinical trial evaluating the efficacy and safety of Merck's all-oral, once-daily regimen combining MK-5172, an investigational hepatitis C virus (HCV) NS3/4A protease inhibitor, and MK-8742, an investigational HCV NS5A replication complex inhibitor. In these co-infected patients, the administration of MK-5172/MK-8742 for 12 weeks resulted in robust HCV suppression, and a safety profile consistent with that observed for patients infected with HCV Genotype 1 infection (GT1) alone.

At 12 weeks, 100 percent (29/29) of co-infected patients who received MK-5172/MK-8742 and ribavirin (RBV), and 90 percent (26/29) of co-infected patients who received MK-5172/MK-8742 alone had HCV RNA levels of less than 25 IU/mL, versus 100 percent (13/13) in patients with HCV alone treated with MK-5172/8742. The data were presented at the 21^st Conference on Retroviruses and Opportunistic Infections (CROI).

“We are encouraged by the potential of MK-5172/MK-8742 for the treatment of people living with HIV/HCV co-infection, where there remains a need for additional therapeutic options,” said Dr. Eliav Barr, vice president, Infectious Diseases, Merck Research Laboratories.

About the MK-5172/MK-8742 Data Presented at CROI

After 4 weeks of treatment, all co-infected patients showed a reduction in HCV RNA levels to below 25 IU/mL with or without RBV administration. HCV kinetics over the first 4 weeks of therapy were similar in patients with or without HIV co-infection.

Virologic Response: Intent-to-Treat Population

*One HIV/HCV co-infected patient had not yet reached TW12; HIV/HCV co-infected (RBV-free) arm: 1 lost to follow-up (HCV RNA undetectable at the last visit on record); 2 breakthroughs with low blood levels of MK-5172 and/or MK-8742; HCV mono-infected (RBV-containing) arm: 3 early discontinuations (day 3 [detectable at the last visit] and days 22 and 35 [undetectable at the last visit]).

There were three treatment failures in the HIV/HCV co-infected study arms; one subject completed the treatment regimen but was lost to follow-up (HCV RNA undetectable at the last visit on record); and two co-infected subjects with low pharmacokinetic levels of MK-5172 and/or MK-8742 experienced virologic breakthrough at the 8 week time point (both cases with low blood levels of MK-5172 and/or MK-8742).

The most common adverse events observed in this cohort were fatigue (7%) and headache (8%). The incidence of these adverse events was not increased in patients with HIV. No co-infected patients discontinued due to either an adverse event or study medication intolerance.

About HIV/HCV Co-Infection

Globally, approximately seven million patients are co-infected with HIV and HCV. HCV is the leading cause of morbidity and mortality among those living with HIV-1, and compared to the general population, the overall prevalence of HCV infection is higher among those infected with HIV-1. Furthermore, HIV/HCV co-infected patients have a three times higher rate of progression to cirrhosis and a six times higher risk of hepatic decompression than HCV patients infected with HCV alone, underscoring the need for new therapeutic options for this patient population.

About the C-WORTHY Clinical Trial

C-WORTHY is a randomized, dose-responsive, parallel-group, multiple-site, open-label trial comparing different patient populations exposed to different durations of treatment of MK-5172 (100 mg QD) in combination with MK-8742 (50 mg QD) with or without RBV in patients with chronic HCV infection. A total of 450 patients with HCV GT1 and HCV RNA levels of ≥10,000 IU/mL have been enrolled in C-WORTHY and randomized across 16 arms to examine difficult-to-treat subpopulations.

The primary objective of C-WORTHY is to evaluate the safety and efficacy of MK-5172 in combination with MK-8742 with or without RBV as assessed by the proportion of patients achieving sustained virologic response at 12 weeks (SVR12) in treatment-naïve patients and more complex patient groups including prior peginterferon alfa and ribavirin treatment failures, cirrhotic patients and co-infected patients. The aim of the HIV/HCV co-infected arms is to compare on-treatment HCV RNA responses (defined as proportion of patients with HCV RNA <25 IU/mL) in GT1 HIV/HCV co-infected patients treated with MK-5712/MK-8742 with or without RBV with those in mono-infected patients.

In the HIV/HCV co-infection arms, 59 treatment-naïve, non-cirrhotic, GT1 HIV/HCV co-infected patients on a stable antiretroviral regimen (raltegravir + tenofovir or abacavir with either 3TC or FTC) were examined. These subjects were randomized at a 1:1 ratio to receive 12 weeks of MK-5172 (100 mg QD) administered concomitantly with MK-8742 (50 mg QD), with or without twice daily (BID) RBV.

Additional data from Merck’s Phase 2 program for MK-5172/MK-8742 will be presented at the 49^th Annual Meeting of the European Association of the Study of the Liver, April 9-13 in London. Details on the C-WORTHY Study, as well as additional Phase 2 trials for MK-5172 and MK-8742, can be viewed on www.merck.com/clinical-trials.

In October 2013, Merck announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to MK-5172/MK-8742 for treatment of chronic HCV infection.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside of the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebookand YouTube.

Merck Forward-Looking Statement

This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2013 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Contact:

Merck
Media:
Caroline Lappetito, 267-305-7639
or
Ian McConnell, 908-423-3046
or
Investors:
Carol Ferguson, 908-423-4465
or
Justin Holko, 908-423-5088

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New drugs trump interferon in HCV therapy

By: NEIL OSTERWEIL, Family Practice News Digital Network

03/05/14

The era of interferon and ribavirin in the treatment of hepatitis C viral infections appears to be drawing to a close, and few clinicians will mourn the passing of the effective but highly toxic combination, investigators said at the Conference on Retroviruses and Opportunistic Infections.

In patients with hepatitis C virus infection alone or HCV with HIV coinfection, a host of new interferon-free drugs and new combinations are transforming therapy, reported Dr. Jean-Michel Pawlotsky, professor of medicine at the University of Paris-Est.

"Hepatitis C is living a real therapeutic revolution. Everything is changing very fast. We’re now getting infection cure rates higher than 90% with the classes of drugs we have," he said at a briefing.

STARTVerso4

With all of the drugs, the sustained virologic response (SVR) rates "are exactly the same in coinfected patients as they are in monoinfected patients," said Dr. Douglas Dieterich of Mt. Sinai Medical Center, New York.

Courtesy US. Dept of Veterans Affairs
A host of new interferon-free drugs and new combinations are transforming therapy for patients with hepatitis C viral infections, says Dr. Jean-Michel Pawlotsky.

For example, a combination of the protease inhibitor faldaprevir with pegylated interferon alfa-2a plus ribavirin (PR) produced SVR rates at week 4 of follow-up (SVR4) of 74% in HCV/HIV coinfected patients, said Dr. Dietrich, a principal investigator for the STARTVerso4 trial.

In this phase III open-label trial, 308 patients with HCV/HIV coinfection who were treatment naive or relapsed after prior interferon-based therapy were randomly assigned to receive faldaprevir 120 mg daily for 24 weeks or 240 mg for 12 or 24 weeks according to on-treatment response. In both arms, faldaprevir was given on a PR backbone, with duration guided by response to therapy.

For the primary endpoint of SVR12, the investigators saw a 72% rate, with no significant difference between the two dose groups, compared with approximately 80% in monoinfected patients in other phase III studies. There was also no difference in efficacy between patients with or without cirrhosis, he said.

Adverse events included mild hyperbilirubinemia in some patients and interferon side effects.

Simeprevir in coinfection

Dr. Dietrich was also the lead on study C212, which looked at simeprevir (Olysio) on a PR backbone in coinfected patients. The results were similar to those seen with faldaprevir (73.6% overall SVR12).

Interestingly, the presence of the simeprevir-resistant q80K polymorphism did not make a difference in response rates, he said. Among monoinfected patients in prior studies, those with q80k polymorphism had significantly lower SVR rates. The adverse events were also similar to those seen in patients with monoinfection.

PHOTON-1

The PHOTON-1 trial evaluated the first interferon-free regimen (sofosbuvir plus ribavirin) in patients with HCV genotypes 1-3 and HIV.

In this study, patients with HCV and stable HIV infection received sofosbuvir 400 mg and ribavirin 1,000-1,200 mg daily. Treatment-naive patients with HCV genotype 1 and treatment-experienced patients with genotypes 2 or 3 received treatment for 24 weeks, while treatment-naive genotype 2/3 patients received 12 weeks of treatment. Patients on multiple antiretroviral (ART) regimens and those with compensated cirrhosis were included in the study.

The primary efficacy endpoint, SVR12, was achieved in 88% of treatment-naive genotype 2 patients and 67% of genotype 3 patients. In genotype 1 patients, the SVR was approximately 70%, Dr. Dietrich said.

Adverse events were general and limited to anemias, headache, and other symptoms commonly seen with HCV therapies, he added.

SYNERGY trial

Dr. Anita Kohli presented final results from the SYNERGY trial, which looked at combination oral HCV therapy for 6 or 12 weeks (SVR4 results from this trial were presented at the 2013 Liver Meeting).

In this phase II prospective cohort study, 60 treatment-naive patients with HCV genotype 1 were enrolled into one of three arms to receive either sofosbuvir 400 mg with ledipasvir 90 mg once daily in a fixed-dose combination for 12 weeks (arm A); the same fixed-dose combination plus the non-nucleoside NS5B inhibitor GS-9669 500 mg/day for 6 weeks (arm B); or the fixed-dose combination plus the NS3 protease inhibitor GS-9451 80 mg/day for 6 weeks.

The SVR12 rate among the patients on sofosbuvir/ledipasvir alone (arm A) was 100%, the rate in arm B was 95%, and the rate in arm C was 100%.

"We find these results very promising," said Dr. Kohli of the National Institutes of Health.

She noted that all patients in the trial were treatment naïve, and that all stages of liver disease were included in the 12-week treatment arm, but cirrhotic patients were excluded from the 6-week arms.

"These regimens are very simple. They’re one, two, or three pills a day," she noted. In addition, "our patient population is one that has been historically very difficult to treat, that is, predominantly African American," she noted.

Most of the patients had genotype 1a with a high viral load, and 25%-30% of patients in all treatment arms had advanced-stage liver disease, she added.

PEARL-III

The PEARL III trial looked at 419 treatment-naive, noncirrhotic patients with HCV genotype 1b, who were randomly assigned to receive either a ritonavir-boosted protease inhibitor (ABT-450) with ABT-267, which is an inhibitor of HCV NS5A, coformulated into a single pill; or ABT-333, a non-nucleoside polymerase inhibitor, with or without ribavirin.

In the ribavirin-containing arm, SVR12 was 99.5%, compared with 99% among controls. There was only one virologic failure in the study, and two patients who did not achieve SVR4 were lost to follow-up at week 12, noted Dr. Daniel Cohen of AbbVie Pharmaceuticals.

Adverse events included predominantly mild headache and fatigue in about 25% of patients, with slightly more events seen in the ribavirin combination arm.

STARTVerso4 was sponsored by Boehringer Ingelheim. C212 was sponsored by Janssen. SYNERGY was supported by the National Institutes of Health and Gilead Sciences. Dr. Cohen is employed by AbbVie, which sponsored PEARL III.

Source

CROI 2014: HCV Abstract and Poster Presentation Coverage by Jules Levin (NATAP)

21st Conference on Retroviruses and
Opportunistic Infections
Boston MA
March 3 - 6, 2014

Reported by Jules Levin

(All links open into new windows)

• ABT-493, a Potent HCV NS3/4A Protease Inhibitor With Broad Genotype Coverage - (03/05/14)
• ABT-530, an HCV NS5A Inhibitor With Potent Pangenotypic Activity and High Genetic Barrier to Resistance - (03/05/14)
• All-Oral Combination of Daclatasvir, Asunaprevir, and BMS-791325 for HCV Genotype 1 Infection - (03/04/14)
• Daclatasvir in Combination With Simeprevir With or Without Ribavirin for Hepatitis C Virus Genotype 1 Infection - (03/04/14)
• All-Oral Therapy With Sofosbuvir Plus Ribavirin For the Treatment of HCV Genotype 1, 2, and 3 Infection in Patients Co-infected With HIV (PHOTON-1) - (03/04/14)
• Three-DAA Regimen (Abbvie) Achieves 99% SVR12 Rates in HCV Genotype 1b Naives - written by Mark Mascolini - (03/04/14)
• Simeprevir Plus PegIFN/RBV Yields 74% SVR12 in HCV/HIV Patients - written by Mark Mascolini - (03/04/14)
• SVR12 72% With Faldaprevir Plus PegIFN/RBV in Naives With HCV/HIV - written by Mark Mascolini - (03/04/14)
• Combination Oral, Hepatitis C Antiviral Therapy for 6 or 12 Weeks: Results of the SYNERGY Trial - (03/04/14)
• Simeprevir plus PegIFN/ribavirin in HCV genotype-1/HIV-1 co-infection (Study C212) - (03/04/14)
• Double or Triple DAA Therapy for HCV-1 Yields 95-100% SVRs in 6 or 12 Weeks (SYNERGY Study) - written by Mark Mascolini - (03/04/14)
• PEARL III: SVR ≥99% AFTER 12 WKS OF ABT-450/R/267 + ABT-333 ± RBV IN TREATMENT-NAIVE HCV GT1B INFECTION - (03/04/14)

Source NATAP

Enanta Pharmaceuticals Announces New Data Presented on Protease Inhibitor ABT-493 at the CROI 2014

Enanta Pharmaceuticals Announces New Data Presented on Protease Inhibitor ABT-493 at the 21st Conference on Retroviruses and Opportunistic Infections (CROI)

WATERTOWN, Mass.--(BUSINESS WIRE)--Mar. 4, 2014-- 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 new in vitro data on ABT-493, a potent NS3/4 protease inhibitor, was presented today during a poster session at the 21^st Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.

ABT-493 is a next-generation HCV NS3/4A protease inhibitor identified within the Enanta-AbbVie collaboration. Designed to enable once-daily dosing without ritonavir, ABT-493 is expected to be co-formulated with AbbVie’s next-generation NS5A inhibitor, ABT-530.

Data from poster number 636 titled “ABT-493, a Potent HCV NS3/4 Protease Inhibitor with Broad Genotypic Coverage”, demonstrates that ABT-493 has a substantially improved in vitro profile compared to earlier generation HCV NS3/4A protease inhibitors and displays potent and broad genotypic activity in genotypes 1a, 1b, 2a, 3a, 4a and 6a, against which many other HCV NS3/4A protease inhibitors have significantly lower potency.In vitro ABT-493 retains potency against most of the clinically important resistance-associated variants in genotype 1 and is fully active against variants resistant to NS5A or NS5B inhibitors. It demonstrates additive to synergistic antiviral activity in vitro when combined with next-generation NS5A inhibitor ABT-530.

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 in some cases 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-resistantStaphylococcus aureus) infections.

Forward Looking Statement

This press release contains forward-looking statements, including with respect to our expectation regarding how ABT-493 will be co-formulated with ABT-530 and the prospects for ABT-493’s activity against multiple genotypes of HCV. 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 results of further preclinical and clinical studies of ABT-493-containing regimens, the development, regulatory and marketing efforts of AbbVie (our collaborator on ABT-493 and on our collaboration’s initial protease inhibitor, ABT-450), and clinical development and marketing efforts of others for 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

Source

All-Oral HCV Regimen Works in 9 Out of 10: Daclatasvir+Asunaprevir+BMS-791325 – CROI 2014

Published: Mar 4, 2014
By Ed Susman , Contributing Writer, MedPage Today

BOSTON -- An all-oral, 12-week regimen appears to successfully treat hepatitis C virus (HCV) infection in about 90% of patients, researchers reported here.

Of the 166 treatment-naive patients in the study, 92% achieved a sustained virologic response at 12 weeks (SVR-12) on the combination of the investigative NS5A inhibitor daclatasvir, the protease inhibitor asunaprevir and the non-nucleoside BMS-791325, said Trevor Hawkins, MD, chief medical officer at Southwest CARE Center and professor of medicine at the University of New Mexico in Santa Fe.

"The observed analysis showed a 92% SVR₁₂, and in the modified intent-to-treat analysis -- wherein data at week 12 is counted as failure if it is missing -- [it] was 89%," Hawkins toldMedPage Today at the annual Conference on Retroviruses and Opportunistic Infections.

A cure in the context of HCV is a sustained virologic response (SVR) -- defined as undetectable viral RNA at some prespecified point after ending therapy, usually 12 or 24 weeks.

At the end of treatment in Hawkins' study, 97.5% of those in the low-dose BMS-971325 group showed a complete viral response compared with 94.2% of those taking the high dose; the SVR₄ was 92.4% in the low-dose group and 91.7% in the high-dose-treated patients. The SVR₁₂was achieved by 92.2% in the low-dose treatment group and by 91.7% of those taking high-dose BMS-791325, the researchers reported.

In the trial, Hawkins said that 9% of the patients were diagnosed with cirrhosis. He said that there did not appear to be a difference in outcome among the cirrhotic patients compared with those who were not cirrhotic -- 13 of the 15 cirrhotic patients achieved an SVR₁₂.

Hawkins said that the next trials -- called UNITY 1 and UNITY 2 -- will separate cirrhotic and noncirrhotic patients to examine if there are differences in outcomes depending on the extent of liver disease. These trials will use the 75-mg dose of BMS-791325.

The trial he reported here showed that patients were able to tolerate the regimen. "There were two discontinuations due to adverse events in the entire 166-patient cohort," he said at a press conference.

The patients diagnosed with HCV genotype 1 were randomly assigned to receive a twice-daily regimen of daclatasvir 30 mg, asunaprevir 200 mg and BMS-791325 at 75 mg or 150 mg for 12 weeks. Hawkins said outcomes were similar for the 80 patients on BMS-791325 given 75 mg twice daily and the 86 patients given BMS-791325 at a dose of 150 mg twice daily.

"There were 11 virologic failures and we attempted to find out if there were any predictors of failure," he said. "The only thing that appeared to predict failure was being of genotype 1a. We tried to determine if there were any polymorphisms at baseline that would predict virologic failure, but we were unable to do that. There really was no obvious correlation."

In pilot studies, the 24-week SVR was 94% and the 12-week SVR was 94% with use of the 75-mg dose of BMS-791325; with the 150-mg dose, the 24-week SVR was 94% and the 12- week SVR was 89%.

The patients were about 54 years old, 67% were men, 83% were white, 82% were genotype 1a, and 15 patients in the study -- 9% -- were diagnosed with cirrhosis.

"This looks good," press conference moderator Jean-Michel Pawlotsky, MD, of the Hôpital Henri Mondor Creteil/University of Paris-Est, told MedPage Today. "There are several potential combinations that are going to work in patients with HCV. This combination with three drugs has good potency and a high barrier to resistance. This is promising."

The study was sponsored by Bristol-Myers Squibb.

Hawkins disclosed commercial interests with Gilead, Janssen, AbbVie, Bristol-Myers Squibb, BMS, Vertex, GlaxoSmithKline, Sangamo, Salix, Merck and ViiV. Co-authors include Bristol-Myers Squibb employees.

Pawlotsky had no disclosures.

Source

HIV No Bar to HCV Therapy With New Agents

Published: Mar 4, 2014

By Michael Smith, North American Correspondent, MedPage Today

BOSTON -- New drugs for hepatitis C mean HIV co-infection is no longer a barrier to successful HCV treatment, researchers said here.

Three studies using different medications in co-infected patients all found cure rates similar to the same drugs in people who had only HCV, according to Douglas Dieterich, MD, of Mount Sinai Hospital in New York City.

"All of these drugs work remarkably well in co-infection," Dieterich told reporters at the annual Conference on Retroviruses and Opportunistic Infections.

Dieterich presented some details of phase III studies of faldaprevir, an investigational HCV protease inhibitor used with pegylated interferon-alfa and ribavirin; simeprevir (Olysio), a protease inhibitor approved for use with interferon and ribavirin; and sofosbuvir, an HCV NS5B inhibitor used with ribavirin.

All three medications are "direct-acting agents" -- they target aspects of viral replication, in contrast to interferon, which boosts the patient's immune system, and ribavirin, which is a general antiviral drug.

In all three studies, Dieterich said, the rate of cure was "exactly the same in co-infected patients as they are in mono-infected patients." A cure in the context of HCV is a sustained virologic response (SVR) -- defined as undetectable viral RNA at some prespecified point after ending therapy, usually 12 or 24 weeks.

The results of the trials are "good news" but not entirely surprising, commented Jean-Michel Pawlotsky, MD, PhD, of Henri Mondor University Hospital in Créteil, France, who moderated a press conference at which some details were presented.

Investigators had been seeing similar results with the first approved direct-acting agents, the protease inhibitors telaprevir (Incivek) and boceprevir (Victrelis), Pawlotsky told MedPage Today.

But treatment just with peginterferon and ribavirin -- for years the only available HCV therapy -- was more difficult for people who also had HIV. "The main difference was due to interferon," Pawlotsky said. "These patients were not responding well to interferon."

One implication, he said, is that in the future, separate trials in co-infected patients might not be needed in order to get approval for new direct-acting agents.

"A trial in mono-infected patients might lead to approval for co-infected patients as well," he said.

Dieterich said the so-called STARTVerso4 was intended to test the efficacy and safety of two different doses of faldaprevir, in combination with peginterferon and ribavirin, in 308 patients with genotype 1 of HCV.

Almost all the patients -- 96% -- were also on highly active antiretroviral therapy for HIV.

The overall SVR rate 12 weeks after the end of treatment (SVR₁₂), he said, was 72% and did not differ significantly between the two doses; phase III results in mono-infected patients were about 80%.

The simeprevir trial (dubbed Study C212) was also investigating the safety and efficacy of the drug among 108 HIV patients with genotype 1 HCV. The drug is approved for mono-infected patients.

In the trials used to support approval, the SVR rates were about 80% in treatment-naive and previously treated but relapsed patients, although they were lower -- 53% to 65% -- among patients who responded either partly or not at all to therapy with peginterferon and ribavirin.

In the co-infected cohort, Dieterich said, the SVR₁₂ rate was 74%. Interestingly, a mutation that usually predicts poor response to interferon -- the Q80K polymorphism -- had no effect, he said, although its presence made a significant difference among mono-infected patients.

In both studies, the drugs were well-tolerated, he said, and the safety profile was similar to what has been seen in mono-infected patients, with most of the adverse events related to interferon.

The final study, dubbed PHOTON-1, looked at sofosbuvir and ribavirin in 223 co-infected patients with several HCV genotypes and differing treatment status.

But overall, he said, SVR12 rates ranged from 70% to 90%, depending on genotype, and in most cases were "exactly the same as in mono-infected patients." SVR₂₄ rates did not change, except for one patient with genotype 1 who appeared to be re-infected after achieving SVR₁₂.

The regimen, he noted, is the first interferon-free regimen to be tested in HIV/HCV co-infected patients.

The regimen was well-tolerated, he said, with only a handful of patients stopping treatment owing to adverse events.

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

AbbVie to Present Late-brealer Pearl-III Study in Patients with Chronic Hepatitis C at CROI 2014

-- SVR(12) RATES OF 99 PERCENT WITH AND WITHOUT RIBAVIRIN WERE ACHIEVED IN GENOTYPE 1B PATIENTS NEW TO TREATMENT

-- RESPONSE RATES IN PEARL-III WERE ALSO HIGH IN SPECIFIC PATIENT CHARACTERISTICS, SUCH AS GENDER, RACE AND GENETICS

Mar 3, 2014

BOSTON, March 3, 2014 /PRNewswire/ -- The first detailed results from AbbVie's (NYSE: ABBV) pivotal phase III study, PEARL-III, were presented today as part of the 21st Conference on Retroviruses and Opportunistic Infections (CROI) press conference and will also be presented as a late-breaker at the conference on March 4. PEARL-III evaluated the efficacy and safety of 12 weeks of treatment with AbbVie's investigational therapy with or without ribavirin (RBV) in non-cirrhotic, adult patients with chronic genotype 1b (GT1b) hepatitis C virus (HCV) infection who were new to treatment.

The PEARL-III study met its primary and secondary endpoints. In the 419-patient study, sustained virologic response rates 12 weeks post-treatment (SVR₁₂) of 99.5 and 99.0 percent were achieved with the AbbVie regimen with and without RBV, respectively. There were no study drug discontinuations due to adverse events.

"Results from PEARL-III are encouraging, as they demonstrate AbbVie's regimen can achieve high rates of SVR, with and without ribavirin across several patient characteristics in those with genotype 1b chronic hepatitis C infection," said Peter Ferenci, M.D., professor of Gastroenterology and Hepatology, Medical University of Vienna.

PEARL-III enrolled patients across different demographics and characteristics. Response rates in patients with certain characteristics (male gender, Black race and IL28B non-CC genotypes) were examined, as these patient populations have historically been associated with having a decreased response to treatment. High response rates were observed across all patients in the study, including those with these characteristics.

"We are excited about the strong PEARL-III results which demonstrate the AbbVie regimen achieved high SVR rates with no discontinuations due to adverse events in patients new to treatment with genotype 1b infection," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "Additionally, with these data, we continue to be on track to begin major regulatory submissions in the second quarter of 2014. AbbVie will continue to disclose additional detailed phase III study results at future scientific congresses and in publications."

About Study M13-961 (PEARL-III)
PEARL-III is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with AbbVie's regimen with and without RBV in non-cirrhotic, GT1b HCV-infected, treatment-naive adult patients.

The study population consisted of 419 GT1b treatment-naive patients with no evidence of liver cirrhosis: 209 patients randomized to the regimen without RBV for 12 weeks, and 210 patients randomized to the regimen with RBV for 12 weeks. Following 12 weeks of treatment, 99.0 percent receiving the regimen without RBV (n=207/209) and 99.5 percent receiving the regimen with RBV (n=209/210) achieved SVR₁₂. Patients in the treatment arm without RBV received placebo in substitution for RBV.

Patients with different demographics and characteristics were enrolled in the study, including gender, race (Black vs. non-Black), Hispanic/Latino ethnicity, age, geographic region, body mass index (BMI), liver fibrosis stage, IL28B genotype and viral load.

Across treatment arms in PEARL-III, there were no documented relapses within 12 weeks post-treatment. No on-treatment virologic failures occurred in the treatment arm without RBV and a single virologic failure occurred in the treatment arm with RBV. While all patients in the study completed therapy, two patients in the arm without RBV were lost to follow-up and therefore were considered treatment failures.

The most commonly reported adverse events (>10 percent for either arm) were headache, fatigue, pruritus, nausea and asthenia, with pruritus and nausea occurring at a statistically higher rate in the treatment arm with RBV compared to the arm without RBV. Anemia occurred more commonly among patients in the RBV-containing arm with clinically significant anemia requiring RBV dose reductions occurring in 9 percent of these patients. 

Additional information about AbbVie's phase III studies can be found on www.clinicaltrials.gov.

About AbbVie's Investigational HCV Regimen
The AbbVie investigational regimen consists of the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg), dosed once daily, and ABT-333 (250mg) with or without RBV (weight-based), dosed twice daily. The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations.

AbbVie's HCV Development Program
The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating an interferon-free, all-oral regimen with and without RBV with the goal of producing high SVR rates in as many patients as possible, including those that typically do not respond well to treatment, such as previous non-responders to interferon-based therapy or patients with advanced liver fibrosis or cirrhosis.

ABT-450 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of HCV.

Safety Information for Ribavirin and Ritonavir
Ribavirin and ritonavir are not approved for the investigational use discussed above, and no conclusions can or should be drawn regarding the safety or efficacy of these products for this use.

There are special safety considerations when prescribing these drugs in approved populations.

Ritonavir must not be used with certain medications due to significant drug-drug interactions and in patients with known hypersensitivity to ritonavir or any of its excipients.

Ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus and must not be used alone for this use. Ribavirin causes significant teratogenic effects and must not be used in women who are pregnant or breast-feeding and in men whose female partners are pregnant. Ribavirin must not be used in patients with a history of severe pre-existing cardiac disease, severe hepatic dysfunction or decompensated cirrhosis of the liver, autoimmune hepatitis, hemoglobinopathies, or in combination with peginterferon alfa-2a in HIV/HCV co-infected patients with cirrhosis and Child-Pugh score greater than or equal to 6.

See approved product labels for more information.

About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories.  The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases.  AbbVie employs approximately 25,000 people worldwide and markets medicines in more than 170 countries.  For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com.  Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

Forward-Looking Statements
Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.

Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2012 Annual Report on Form 10-K/A, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

SOURCE AbbVie

For further information: Media: Elizabeth Hoff, +1 (847) 935-4236, elizabeth.hoff@abbvie.com, or Javier Boix, +1 (847) 937-6113, javier.boix@abbvie.com; Investor Relations: Elizabeth Shea, +1 (847) 935-2211, elizabeth.shea@abbvie.com

Source

Hepatitis C to Share Spotlight at HIV Conference

Medscape Medical News > Conference News

Marcia Frellick

February 24, 2014

BOSTON — Although HIV will dominate the agenda at the 2014 Conference on Retroviruses and Opportunistic Infections (CROI), related viruses and infections will also be in the limelight.

Several presentations at the conference, being held from March 3 to 6, will focus on advances in the treatment of hepatitis C virus and the barriers to delivery, and the latest developments in tuberculosis (TB) and human papillomavirus.

Lynn Taylor, MD, from the division of infectious diseases at Miriam Hospital, Brown Medical School, in Providence, Rhode Island, told Medscape Medical News that developments in drugs and policy on the hepatitis C front make this year's discussion particularly important.

"We have seen extraordinary, unprecedented improvement in therapies to cure hep C," she said. "We have the potential to eradicate hep C locally, nationally, globally. The focus of our panel is that there's nothing in place yet, on any significant scale, to enhance delivery."

Dr. Taylor described a "crisis" in the United States because baby boomers who never knew they were infected are now discovering it in advanced form. "Seventy-five percent of Americans who have hep C don't even know they have it," she said.

“Ten years ago, you were considered a charlatan if you said hep C was curable.”

Last year, because of the prevalence of hepatitis C in baby boomers, the Centers for Disease Control and Prevention revised its guidelines to recommend a 1-time screening for everyone born from 1945 to 1965, in addition to risk-based screening. In December 2013, the European Association for the Study of the Liver revised its clinical practice guidelines on the management of hepatitis C; they will be presented in April before the International Liver Congress.

Dr. Taylor said she is "thrilled" to see the increased attention on hepatitis C at the conference.

"Ten years ago, you were considered a charlatan if you said hep C was curable," she said.

The conference, the most significant HIV research meeting in the world, will attract more than 4000 leading international HIV/AIDS researchers. The goal is to provide a forum for researchers to translate their findings into direct progress in HIV.

Conference to Draw More Than 4000 Researchers

Last year's conference was abuzz with the news that a 2-year-old Mississippi girl, born with HIV and treated early with antiretroviral drugs, had been functionally cured and no longer had detectable levels of the virus, despite not taking medication for 10 months.

This year, speakers will provide updates on the progress toward a cure for HIV, and look at what is standing in the way of getting there.

Adeeba Kamarulzaman, MBBS, from the University of Malaya in Kuala Lumpur, Malaysia, said she will explain some positive changes for drug users in the HIV fight in countries such as Malaysia.

She will also speak about the impact of the "epidemic of incarceration" and its effects on HIV, as well as coinfection with TB and hepatitis C, she told Medscape Medical News. She will highlight the increase in methamphetamine use and its relation to HIV risk behaviors, particularly in men who have sex with men.

TB is also getting attention at the conference. There will be presentations on the resistance, persistence, monitoring, and control of the disease; the use of novel imaging technology to monitor treatment response; and population-level control of HIV-related TB.

The prevention and treatment of HIV infection in infants will be addressed, as will the short- and long-term consequences of antiretroviral exposure during pregnancy and breast-feeding.

In addition, the outbreak of invasive meningococcal disease that affected men who have sex with men in New York City from 2010 to 2013 will be discussed.

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CROI Abstract Submissions Now Open, and Old CROI Website Still “Lost” in Cyberspace

HIV and ID Observations

Paul E. Sax, MD

Editor-in-Chief NEJM Journal Watch HIV/Aids Clinical Care September 20th, 2013

HIV researchers can now submit their abstracts to the 2014 Conference on Retroviruses and Opportunistic Infections – or “CROI”.

(It rhymes with “soy”, as in “soy sauce”; or, if you prefer, “oy”, as in “oy vey”.)

Further details here. General submission for abstracts closes on October 8.

Meanwhile, people continue to wonder what happened to the now defunct CROI website, retroconference.org (not hyperlinked because there’s nothing there).

It’s not just nostalgia — that site was an invaluable repository of abstracts, posters, and web casts, the go-to place for a staggering amount of pre-publication HIV research. Many have despaired that finding the right reference for their grant and paper now requires all kinds of Google wizardry.

And just check out the abstract links in this Really Rapid Review© — all dead. Blah.

You could try this — but the searches don’t really work, it’s just a tease.

So what’s up? Here’s what it says about past CROI material on on the current site:

We would like to acknowledge that the previous CROI website: www.retroconference.org and the associated materials (abstracts, webcasts, etc), are not available at this time. The CROI Foundation previously partnered with a conference manager that constructed, owned, maintained, and has proprietary rights to the display formats and graphical elements of the website. The former website was taken off line by the former manager. The CROI Foundation fully appreciates how important the content from the prior CROI website is to the colleagues and the community it serves and efforts are underway to recover the content from prior conferences …

So why would someone take this information off-line? Additional details here – some sort of  legal fight.

Let’s hope is can be resolved soon, as much of that archived CROI material was very useful.

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