The European Commission has approved the Bristol-Myers Squibb (BMS) drug candidate Daklinza® (daclatasvir) in combination with other treatments across genotypes 1, 2, 3, and 4 for chronic hepatitis C virus (HCV) in adults—the first pan-genotypic NS5A complex inhibitor approved for use in Europe.
BMS says Daklinza plus other drugs will enable a shorter 12- or 24-week treatment duration compared to 48 weeks for interferon- and ribavirin-based regimens. Four combinations of treatments and/or regimens are recommended by BMS, depending on the genotype being targeted:
- Daklinza plus sofosbuvir for 12 weeks against Genotype 1 or 4 without cirrhosis.
- Daklinza plus sofosbuvir for 24 weeks against Genotype 1 or 4 with compensated cirrhosis.
- Daklinza plus sofosbuvir and ribavirin against Genotype 3 with compensated cirrhosis and/or treatment experienced.
- Daklinza for 24 weeks plus 24 to 48 weeks of peginterferon alfa and ribavirin against Genotype 4
The Daklinza–sofosbuvir combination, according to BMS, provided cure rates of up to 100% in clinical trials, including patients with advanced liver disease, genotype 3 and those who have previously failed treatment with protease inhibitors.
“The eradication of HCV is in sight, and with today’s approval, Daklinza, in combination with other agents, will be an important option to achieve cure across many HCV genotypes and patient types for those in the EU who are in dire need of new treatment choices,” Emmanuel Blin, BMS’ head of worldwide commercialization, said in a statement.
The EC decision came about two months after Daklinza received a positive opinion for combination use from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP). Daklinza underwent the accelerated review process in Europe afforded to new medicines deemed to have major public health interest because it meets an unmet medical need.
CHMP said its decision was based on results of a pivotal trial in which Daklinza was evaluated in HCV genotype-1, -2 and -3 infected patients, in combination with sofosbuvir with or without ribavirin. Daklinza plus sofosbuvir achieved sustained virologic response 12 weeks after the end of treatment in 99% of treatment-naïve patients with HCV genotype 1, 100% of patients with genotype 1 who had failed treatment with telaprevir or boceprevir, 96% of those with genotype 2 and 89% of those with genotype 3.
The trial included a treatment arm with patients that previously failed on therapy with an NS3/4A inhibitor in combination with pegylated interferon and ribavirin. All those patients reached a sustained virologic response. BMS said additional daclatasvir-plus-sofosbuvir trials are being conducted 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.
The pivotal study cited by CHMP was supported by an earlier trial of Daklinza with pegylated interferon and ribavirin in patients with genotype 4 infection, and by several phase IIb trials of Daklinza with other combinations including with pegylated interferon and ribavirin.
In the U.S., the FDA has granted priority review status for Daklinza-based treatment regimens. The FDA has set a target review date under the Prescription Drug User Fee Act (PDUFA) of November 30, 2014.
Earlier this year, the FDA granted its Breakthrough Therapy Designation to Daklinza and Sunvepra (asunaprevir) as a combination therapy for genotype 1b HCV infection.
Last year, BMS won a similar designation for the investigational all-oral “3DAA” regimen consisting of daclatasvir, asunaprevir, and experimental drug BMS-791325, enabling the company to speed up the start of its ongoing Phase III UNITY Program. Study populations include non-cirrhotic naïve, cirrhotic naïve and previously treated patients. The 3DAA regimen is being studied as a fixed-dose-combination treatment with twice-daily dosing.
BMS hopes the Phase III results for 3DAA will be at least as strong as its Phase II results announced in 2012. 3DAA achieved sustained virologic response 12 weeks post-treatment in 15 of 16 treatment-naïve, genotype 1 chronic HCV patients in a Phase II study. The 16th achieved sustained virologic response at 24 weeks post-treatment.
In Japan, Daklinza was approved last month in combination with Sunvepra, an NS3/4A protease inhibitor, as that nation’s first all-oral, interferon- and ribavirin-free treatment regimen for patients with genotype 1 chronic HCV infection, including those with compensated cirrhosis.