ALLY 3+ TRIAL INVESTIGATING DAKLINZA (DACLATASVIR) IN COMBINATION WITH SOFOSBUVIR AND RIBAVIRIN DEMONSTRATES HIGH CURE RATES IN CHRONIC HEPATITIS C GENOTYPE 3 PATIENTS WITH ADVANCED FIBROSIS OR CIRRHOSIS
Daclatasvir+sofosbuvir+ribavirin regimen achieves SVR12 rates of 88% and 92% overall for 12 or 16 weeks of therapy respectively in GT-3 patients with advanced fibrosis or cirrhosis
Bristol Myers-Squibb today announced late-breaking data from the Phase 3 ALLY-3+ Trial investigating a regimen of Daklinza™ (daclatasvir, DCV) in combination with sofosbuvir (SOF) and ribavirin (RBV) in genotype 3 hepatitis C (HCV) patients with advanced fibrosis or cirrhosis, for treatment durations of 12 and 16 weeks. This patient population is one of the most difficult to treat, among whom sustained virologic response (SVR) rates, or cure, have proved harder to achieve with existing therapies.
The results show that SVR12 rates in cirrhotic patients only were 83 per cent and 89 per cent in the 12- and 16-week arms, respectively. Results will be presented at The Liver Meeting® 2015, the Annual Meeting of The American Association for the Study of Liver Diseases (AASLD), in San Francisco, CA, November 13 – 17.
Daklinza is a potent, pan-genotypic NS5A replication complex inhibitor (in vitro) that has been approved for use in combination with sofosbuvir (marketed in Canada by Gilead Sciences Canada Inc. as SOVALDI™) as a convenient, all-oral, once-daily regimen for the treatment of adult patients with hepatitis C genotypes 1 and 2 with compensated liver disease including cirrhosis. Daklinza has also received a Notice of Compliance with conditions (NOC/c) from Health Canada for the treatment of genotype 3 patients with compensated liver disease including cirrhosis. In Canada, genotypes 3 accounts for 20 per cent of hepatitis C infections.
Daklinza is contraindicated in combination with medicinal products that strongly induce CYP3A and P-glycoprotein transporter, as this may lead to lower exposure and loss of efficacy of Daklinza. Daklinza must not be administered as a monotherapy.
“Patients with genotype 3 hepatitis C infection make up about one in five cases of hepatitis C infection in Canada,” said Dr Alnoor Ramji, Clinical Associate Professor of Medicine, Gastroenterology and Hepatology at the University Of British Columbia. “High cure rates for these patients have remained elusive, so this data is very encouraging. These cure rates significantly improve upon what we have seen in the past in patients with advanced fibrosis or cirrhosis and offer more hope for a high unmet medical need.”
In the ALLY-3+ study, the daclatasvir+sofosbuvir+ribavirin combination regimen had no discontinuations due to adverse events (AEs) or treatment-related serious AEs. The eight frequent AEs were insomnia (30%), fatigue (26%) and headache (24%). Additionally, relapse occurred in four patients (two in the 16-week and two in the 12-week arm). There was one death (12-week arm; not treatment-related). There were no virologic breakthroughs.
“Our continued scientific exploration of the potential for Daklinza used in combination with other direct-acting antivirals for HCV patients has yielded these encouraging results,” said Douglas Manion, M.D., Head of Specialty Development, Bristol-Myers Squibb. “We remain committed to delivering therapeutic options to HCV patients with unmet needs around the globe, including those with more complicated disease and other difficult-to-treat groups such genotype 3 patients with more advanced liver disease who still need help to achieve cure.”
ALLY 3+ Study Design
This open-label, phase 3b study in HCV genotype 3-infected treatment-naive or -experienced patients with advanced fibrosis or compensated cirrhosis randomized patients 1:1 to receive 12 weeks versus 16 weeks of Daklinza (60 mg QD) + SOF (400 mg QD) + RBV (weight-based), stratified by advanced fibrosis or cirrhosis status.
Fifty patients were treated (12 weeks: 24 patients; 16 weeks: 26 patients). The majority of patients were male (80%), white (98%), and treatment-experienced (74%; 10% prior relapse on SOF+RBV); 72 per cent had cirrhosis and 52 per cent had HCV RNA ≥6 million IU/mL. Baseline characteristics were comparable between arms.
The primary endpoint was to estimate SVR12 in treatment-naive or – experienced subjects with compensated advanced fibrosis/cirrhosis (F3-F4) treated for 12 weeks and for 16 weeks.
DAKLINZA Safety Information
The safety of DAKLINZA for the treatment of hepatitis C has been demonstrated in diverse patient populations, including genotypes 1-3, patients with advanced fibrosis or cirrhosis and patients who are interferon-intolerant or who have not previously responded to first-generation protease inhibitor therapy.
DAKLINZA in combination with sofosbuvir resulted in low rates of discontinuation (1%) due to adverse events (AEs).The rate of serious adverse events (SAEs) was low (7%). The most common adverse events were fatigue, headache and nausea.
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 per cent of those infected with hepatitis C will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, left untreated up to 20 per cent of people with chronic hepatitis C will develop cirrhosis; of those, up to 25 per cent may progress to liver cancer. An estimated 350,000 to 400,000 people in Canada are chronically infected with HCV, but about 21 per cent of those people are unaware and are undiagnosed.
About Genotype 3
Affecting an estimated 54.3 million people (30% of all HCV patients) worldwide, genotype 3 is the second most common HCV genotype globally and is considered one of the most difficult to treat. The more aggressive nature of genotype 3 lies in the damage it causes to the liver, as it is associated with accelerated fibrosis progression. Recent research has also shown the risk of cirrhosis for patients infected with HCV genotype 3 is 31 per cent greater than for those with HCV genotype 1.
About Bristol-Myers Squibb in HCV
Bristol-Myers Squibb is focused on helping to eradicate hepatitis C around the world, with a primary emphasis on difficult-to-treat patients, including those millions in countries such as China where population-based HCV solutions remain a high unmet need. Among the company’s data being presented at AASLD this year is the first all-oral, DAA Phase 3 trial in HCV completed in China.
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.
DAKLINZA™ is a trademark of Bristol-Myers Squibb Holdings Ireland, used under licence by Bristol-Myers Squibb Canada.
SOVALDI® is a registered trademark of Gilead Sciences Ireland UC or its related companies.