Today, AbbVie announced that its investigational hepatitis C virus (HCV) infection drug has been granted Breakthrough Therapy designation by the US Food and Drug Administration (FDA).

Its investigational direct-acting antiviral (DAA) combination has been granted this designation with and without ribavirin for the treatment of people with genotype 1 (GT1) hepatitis C. The designation is based, in part, on positive data from AbbVie’s Phase 2b clinical trial M11-652. M11-652 is known as the “Aviator” study, which consisted of 571 patients with GT1 hepatitis C. AbbVie’s program contains three different mechanisms of action, including protease (ABT-450/r), polymerase (ABT-333) and NS5A (ABT-267) inhibitors. Results from the treatment arms evaluating ABT-450/r + ABT-267 + ABT-333 with and without ribavirin showed that the regimen provided high sustained viral response rates (SVR) with 12 weeks of therapy in previously untreated patients, as well as those who had failed prior therapy with pegylated interferon and ribavirin.

“AbbVie is pleased that the FDA has granted Breakthrough Therapy designation to our 3-DAA combination with and without ribavirin. We feel it reflects the potential of this regimen to be important in the treatment of HCV,” John M. Leonard, MD, Senior Vice President and Chief Scientific Officer, AbbVie said in a statement. “Our HCV program is one part of our advancing pipeline which is focused on delivering innovative therapies to address pressing areas of unmet clinical need.”

New results from the trial found that 99 percent of patients who were treatment-naïve achieved sustained viral rates with 12 weeks of therapy and 96 percent achieved sustained viral rates in 24 weeks. For patients that did not respond to prior therapy of pegylated interferon and ribavirin, 93 percent achieved sustained viral rates in 12 weeks and 24 weeks of therapy. These results were presented at the 2013 International Liver Congress in Amsterdam.

The company’s all-oral, triple-DAA combination is being studied in Phase 3 clinical trials including over 2,000 patients with genotype 1 hepatitis C.

Source: AbbVie

Last Updated: 5/6/13; 12:05PM EST

Janssen-Cilag International NV (Janssen) recently announced that it has submitted a Marketing Authorization Application to the European Medicines Agency (EMA) for approval of its investigational hepatitis C drug simeprevir (TMC435).

Simeprevir is a new generation NS3/4A protease inhibitor, which is administered as a once-daily capsule with pegylated interferon and ribavirin for the treatment of genotype 1 or 4 chronic hepatitis C in adult patients with compensated liver disease, with or without HIV-1 co-infection, who are treatment naïve or have previously failed interferon therapy.  Simprevir is currently in phase III development.

“Nine million people across Europe have hepatitis C and 50 to 70 percent are infected with the genotype 1 virus, which can be particularly difficult to cure. Additionally, patients infected with genotype 4 virus lack new treatment options. This filing of simeprevir in Europe represents an important step forward in the process of bringing simeprevir to market and helping to battle this challenging disease,” Wim Parys, Global Head of Development, Infectious Diseases and Vaccines of Janssen stated.

If simeprevir receives approval, it will provide people living with hepatitis C an option of a new generation protease inhibitor-based regimen that includes the investigational drug taken once-daily for 12 weeks in combination with pegylated interferon and ribavirin for 24 or 48 weeks.

Filing for regulatory submission for simeprevir is supported by efficacy data from three Phase III studies, QUEST-1, QUEST-2 and PROMISE in genotype 1 hepatitis C patients. QUEST-1 and QUEST-2 assessed treatment-naïve patients and PROMISE assessed patients who have relapsed after prior interferon-based treatment. Data from a phase II and an ongoing phase III study support the use of simeprevir in patients with genotype 4 hepatitis C.

Simeprevir is jointly developed by Janssen and Medivir AB. Janssen Therapeutics EMEA, a division of Janssen Pharmaceutica NV has the commercialization rights of the drug in EMEA and Medivir AB will commercialize the product in Noridc countries.

According to the World Health Organization, hepatitis C affects approximately 150 million people worldwide and causes 350,000 deaths per year.

Source: Janssen

Last Updated: 4/26/13; 11:15AM EST

Today, Boehringer Ingelheim Pharmaceuticals, Inc. announced positive results from a Phase 3 trial of faldaprevir (BI 201335) in combination with pegylated interferon and ribavirin (PegIFN/RBV) for treatment of patients with hepatitis C.

The pivotal Phase 3 STARTVerso 1 trial showed that previously untreated patients with genotype-1 hepatitis C virus (HCV) who received once-daily faldaprevir plus PegIFN/RBV achieved viral cure when measured 12 weeks after treatment was completed (SVR12). Data showed that 79 percent achieved SVR12 in the 120mg arm, 80 percent achieved SVR12 in the 240mg arm, and 52 percent achieved SVR12 in the group who received PegIFN/RBV plus placebo.

Additionally, data showed that protocol-defined early treatment success (ETS) was achieved by patients who received the faldaprevir-based regimen with 87 percent in the 120mg and 89 percent in the 240mg arm. Achieving ETS means the patients were eligible for an overall shorter treatment duration of 12 weeks of faldaprevir/24 weeks of PegIFN/RBV.  For those who completed treatment early 86 percent (120mg) and 89 percent (240mg) went on to achieve viral cure (SVR12), meaning an overall treatment regimen of 24 weeks was sufficient to achieve viral cure in most patients. This cuts treatment duration in half compared to treatment with PegIFN/RBV alone, which consists of a 48 week treatment duration. A reduction in time patients are exposed to treatment with interferon is a current goal in HCV treatment innovation.

Results will be presented at the EASL’s International Liver Conference (ILC) tomorrow.

“In the STARTVerso 1 study, faldaprevir has shown efficacy in a range of gegnotype-1a and 1b HCV patients with and without cirrhosis,” Principal Investigator Professor Peter Ferenci of the Medical University Vienna said. “The viral cure rates and potential for shorter treatment duration seen in STARTVerso 1 are very encouraging for the many patients currently facing a year of interferon-based treatment.”

Peter Piliero, MD, Vice President, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals Inc., said that the results of the first of the pivotal trials allow the company to move forward in making strides toward the short-term goal of providing hepatitis C patients with a shorter duration of interferon-based regimens. “We are developing faldaprevir as a potential foundation for both interferon-based and interferon-free treatment regimens. We are optimistic that ongoing studies with our pipeline compounds will lead to faldaprevir-based interferon-free regimens for patients with HCV,” Piliero stated.

Source: Boehringer Ingelheim Pharmaceuticals, Inc.

Last Updated: 4/23/13; 1:30PM EST

Today, Merck announced that it has entered into a non-exclusive agreement with Bristol-Myers Squibb to conduct a Phase II trial for a combination regime for treatment of hepatitis C virus (HCV).

The trial will evaluate the safety and efficacy of a once-daily oral combination consisting of Bristol-Myers Squibb’s investigational NS5A replication complex inhibitor daclatasvir and Merck’s investigational NS3/4A protease inhibitor MK-5172 in genotype 1, hepatitis C patients.

“In HCV, agreements like this that combine novel investigational candidates are important to evaluate the potential of novel oral regimens early in the development cycle,” Eliav Barr, MD, Vice President, Infectious Diseases, Project Leadership and Management, Merck Research Laboratories said in a statement. “We are pleased to collaborate with Bristol-Myers Squibb to advance this potential all-oral combination.”

The Phase II clinical trial is planned for initiation following the completion of a Phase I safety evaluation of the combination regimen. Under the terms of the agreement, Merck will conduct the Phase II clinical trial. The agreement does not cover further clinical development activities beyond the Phase II study.

MK-5172 is currently being evaluated in combination with other approved investigational medications in Phase II clinical trials including MK-8742, which is Merck’s investigational orally available HCV NS5A protease inhibitor. Daclatasvir is being extensively studied as a key component of potential direct-acting antiviral (DAA) based hepatitis C treatment regimens. It has been studied in over 4,100 patients to date and is in Phase III development.

Hepatitis C can be a serious, lifelong illness that affects the liver. The disease can lead to long-term health problems or death.

Source: Merck

Last Updated: 4/22/13; 11:45AM EST