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-naive, 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
3 - Phase III
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 were presented this week at the 49th annual meeting of the European Association for the Study of the Liver (EASL) The International Liver CongressTM, in London. Results showed that the 24-week regimen achieved an overall sustained virologic response (a functional cure) 12 weeks after the end of treatment (SVR12) amongtreatment-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.
“The HALLMARK-Dual study results are very encouraging for persons with hepatitis C, particularly those with advanced liver disease,” said Dr. Alnoor Ramji, Clinical Associate Professor of Medicine in the Division of Gastroenterology at the University of British Columbia. “While research in this area is advancing rapidly, there is a high medical need for these potent treatment regimens that are effective in a broad range of patients. Ultimately what we want to see is an increased virologic eradication rates for HCV. The results of this daclatasvir-based study point in that direction.”
These data were part of the company’s recent DCV and ASV NDA submissions to the U.S. FDA, and helped support the validated marketing authorization application to the European Medicines Agency for the use of DCV in combination with other agentsfor 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 studyof this regimenin Japanese patients, which led to the submission of a New Drug Application with Japan’s Pharmaceutical and Medical Devices Agency.
Globally, there are 170 million people infected with HCV, including over 300,000 in Canada, with genotype 1 being the most prevalent.
“I was infected with hepatitis C in 1970 as a result of a blood transfusion. I have survived 43 years with this disease but thanks to recent treatment advances, I am now cured,” said Joan King, Vice President of British Columbia-based HepCBC. “When I talk to other diagnosed patients we are very hopeful because the cure rates for this disease are increasing thanks to research like this.”
Study Design and Results
This Phase III multinational clinical trial included 116 sites in 18 countries, including countries that have a high prevalence of GT1b 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).
- 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 non-cirrhotic (85%) and cirrhotic (84%) 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.
EASL The International Liver Congress is a registered trademark of European Association for the Study of the Liver
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.
About Bristol-Myers Squibb Canada
Bristol-Myers Squibb Canada is an indirect wholly-owned subsidiary of Bristol-Myers Squibb Company, 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 www.bmscanada.ca.