FDA Grants Priority Review, NICE Recommends Daclatasvir

Issue: December 2015

Bristol-Myers Squibb announced the FDA accepted the company’s three supplemental New Drug Applications for review of daclatasvir in combination with sofosbuvir for the treatment of hepatitis C virus infection in the settings of cirrhosis, post-transplant and co-infection while the National Institute for Health and Care Excellence recommended daclatasvir for the treatment of hepatitis C virus genotypes 1, 3 and 4 infection in England and Wales.

The new drug applications include review of daclatasvir (Daklinza, Bristol-Myers Squibb) in combination with sofosbuvir (Sovaldi, Gilead Sciences) with or without ribavirin to treat patients with HCV with decompensated cirrhosis, post-liver transplant recurrence of HCV and HCV/HIV-1 co-infection. The FDA will review the applications within 6 months and, if approved, it “would offer a significant improvement in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions,” according to the release.

“Hepatitis C is not a one-size-fits-all, monolithic disease. Our focus for the Daklinza-sofosbuvir regimen centers on addressing the needs of HCV patient subpopulations who need new options even in light of the extraordinary advances that have occurred in HCV treatment,” Douglas Manion, MD, head of specialty development at Bristol-Myers Squibb, said in the release. “We look forward to working with the FDA toward the goal of eventually helping many difficult-to-treat HCV patients.”

According to the release, the new supplemental applications include clinical data from the ALLY-1 and ALLY-2 trials. ALLY-1 evaluated a 12-week regimen of daclatasvir and sofosbuvir once-daily with ribavirin for patients with HCV with either advanced cirrhosis or post-liver transplant recurrence of HCV. ALLY-2 evaluated the once-daily 12-week combination of daclatasvir and sofosbuvir for patients with HCV/HIV-1 co-infection.

The FDA approved daclatasvir for the treatment of HCV genotype 3 infection in July, after clinical data showed 98% of the treatment-naive patients without cirrhosis and 58% of treatment-naive patients with cirrhosis achieved sustained virologic response with a combination regimen of daclatasvir and sofosbuvir.

In a previous press release, the FDA stated that daclatasvir carries a warning for patients and health care providers following reports of serious slowing of the heart rate and cases requiring pacemaker intervention. These events occurred when amiodarone was co-administered with sofosbuvir in combination with another HCV direct-acting antiviral, including daclatasvir.

NICE Recommendation

“Daclatasvir in combination with other agents represents a much needed oral treatment regimen that has been shown to cure the infection in the majority of patients, and we have already seen positive results in the real-life setting in patients with advanced disease,” Anna Maria Geretti, MD, PhD, FRCPath, professor of virology and infectious diseases, Institute of Infection & Global Health, University of Liverpool, England, said in the release. “In the past, there have been limited treatment options available and therefore, this decision is an important milestone.”

Daclatasvir is currently approved in combination with sofosbuvir for 12 weeks in patients with HCV genotype 3 without cirrhosis and for 24 weeks in patients with cirrhosis with the optional use of ribavirin, according to the release. Therapy options for HCV genotype 3 patients in England have been limited and previously included interferon.

Manion stated in the release: “The burden of genotype 3 hepatitis C in the United Kingdom is one of the highest anywhere in Europe. England has now joined Italy, France, The Netherlands, Sweden, Belgium, Switzerland, Denmark, Scotland and Ireland in recognizing the value of Daklinza for the treatment of genotype 3 HCV, and we are excited to make it available to help address what is still a significant unmet need among the UK HCV population.”

The Committee for Medicinal Products for Human Use of the European Medicines Agency recommended daclatasvir be approved to treat chronic HCV genotype 3 in adults in July 2014.

Disclosures: Manion reports being employed by Bristol-Myers Squibb. HCV Next was unable to confirm relevant financial disclosures of Geretti at the time of publication.