FDA Denies Bristol-Myers Squibb's Daclatasvir For HCV, Citing Asunaprevir Withdrawal

Bristol-Myers Squibb (BMS) says that the Food and Drug Administration (FDA) has denied its daclatasvir New Drug Application (NDA). The denial comes on the heels of BMS’ withdrawal of asunaprevir for consideration. BMS announced the FDA’s decision in a press release, stating that the federal agency communicated through a Complete Response Letter (CRL). Since much of BMS’ data on daclatasvir was gained in combination studies with asunaprevir, now withdrawn, the agency could not move forward with the application. Instead, the FDA is requesting additional data on daclatasvir in combination with other antiviral agents.

Francis Cuss, EVP and CSO at BMS, said, “Despite the recent advances in the treatment of hepatitis C there remain significant areas of unmet high need in this disease area. Our commitment remains to make daclatasvir-based regimens available to help these difficult-to-treat patients achieve cure, and we will continue to collaborate with the FDA to bring daclatasvir to patients in the U.S. as quickly as possible.”

Daclatasvir

Daclatasvir is an NS5A complex inhibitor that shows promise in combination with other agents for the treatment of HCV. BMS’s clinical development consists of trials with other agents and trials in difficult-to-treat patient populations. Those patients include pre- and post-liver transplant (ALLY-1), HCV patients co-infected with HIV (ALLY-2), and patients with genotype 3 (ALLY-3). The Phase 3 UNITY studies are testing a combination of daclatasvir/asunaprevir/beclabuvir.

HCV Treatments

When BMS withdrew asunaprevir from FDA consideration, it cited “the rapidly evolving hepatitis C (HCV) treatment landscape in the U.S.” That landscape is now dominated by Gilead and its blockbuster and expensive drug Sovaldi (sofosbuvir). A combination of sofosbuvir and ledipasvir (Harvoni) is now approved in the U.S., the EU, and Australia.

Also in contention are AbbVie’s ABT-450, ABT-267, and ABT-333. Merck’s acquisitions from Idenix include clinical-phase HCV agents IDX21437, IDX21459, and samatasvir. Enanta Pharmaceuticals joins BMS in re-evaluating the HCV landscape, announcing in October 2014 that it decided not to continue developing ABT-493 with AbbVie.

The competition for effective drugs is high due to the prevalence of HCV worldwide. Gilead’s Sovaldi is leading the race due to its effectiveness, considered to be a cure for the condition. However, there is room for other contenders due to Sovaldi’s high price, which started a heated conversation among patients, insurance companies, healthcare providers, and legislators.