Bristol-Myers Squibb (BMS) said today it has withdrawn its new drug application (NDA) for asunaprevir, an NS3/4A protease inhibitor—and will retreat from plans to pursue a combination Hepatitis C (HCV) treatment consisting of asunaprevir and daclatasvir for patients with HCV genotype 1b.
BMS added that it will continue to pursue FDA approval of daclatasvir, an NS5A complex inhibitor that works across genotypes 1, 2, 3, and 4. Daclatasvir is being studied globally in multiple treatment regimens for HCV patients with high unmet need, according to the company.
In a statement, BMS attributed its decision to “the rapidly evolving hepatitis C (HCV) treatment landscape in the U.S.” That landscape is about to be reshaped by at least two rival drug developers whose HCV combination treatments that are in late stages, have shown successful results, and are expected to win FDA approval.
Gilead Sciences is expected to gain the agency’s nod for the combo of the NS5B inhibitor Sovaldi (sofosbuvir) and the NS5A inhibitor ledipasvir by the PDUFA date of October 10. Sovaldi is already marketed as part of a chronic HCV combination treatment, which, depending on the patient’s type of infection, could combine the drug with ribavirin (RBV), or with ribavirin and peginterferon-alfa (RBV + peg-IFN).
Sovaldi won FDA approval in December 2013 as the first drug that has shown the safety and efficacy to treat certain types of HCV infection without the need for injection of interferon at the same time. Sovaldi’s $84,000 price for a 12-week treatment course has generated criticism from three Democrats in the Republican-majority U.S. House of Representatives, who in March requested “a briefing” on Sovaldi’s pricing from Gilead CEO John C. Martin, Ph.D. Gilead has defended its $1,000-a-pill pricing by noting that the cost of Sovaldi is lower than the cost of complications associated with hepatitis C treatment, such as liver damage or liver failure.
AbbVie submitted its NDA in April for its HCV combination of three drugs, a month after reporting positive results. The combo consists of the protease inhibitor ABT-450 used with the booster ritonavir, the NS5A inhibitor ABT-267, and the non-nucleoside polymerase inhibitor ABT-333.
In a trial in 419 patients, AbbVie’s as-yet-unnamed drug cocktail cured 99 percent of patients after 12 weeks of treatment, according to results presented at the said today at the Conference on Retroviruses and Opportunistic Infections in Boston.
Also interested in HCV combination drug development is Merck & Co., which in June said it was buying Idenix for about $3.85 billion cash. Idenix brings to Merck three clinical-phase HCV drugs under evaluation for potential inclusion in future combination therapies—IDX21437 and IDX21459, both nucleotide prodrugs, and samatasvir, a NS5A inhibitor.
In a statement, BMS said its HCV strategy was geared to meeting unique unmet medical needs in individual markets—such as Japan, where in July the company won approval for its daclatasvir-asunaprevir combo as that nation’s first all-oral, interferon- and ribavirin-free treatment regimen.
“The dual regimen was developed to meet the distinct need of the Japanese patient population, and we believe this treatment has the potential to play a major role in curing HCV patients in Japan, as well as in other markets where the HCV patient population is similar to Japan,” BMS stated.
That’s not the case in Europe where the company won European Union approval in August for daclatasvir—marketed as Daklinza®—in combination with other treatments (sofosbuvir, ribavirin, and peginterferon alfa) across genotypes 1, 2, 3, and 4 for chronic HCV in adults. Daclatasvir was approved as the first pan-genotypic NS5A complex inhibitor approved for use in Europe.
“Similarly, we believe that daclatasvir-based regimens have the potential to fill continued unmet medical need in the U.S. and elsewhere in the world,” BMS said.
To that end, BMS plans to submit additional data for daclatasvir to the FDA from its ongoing clinical trial program, focused on difficult-to-treat patients, including patients with HCV genotype 3, patients who are pre- and post-liver transplant, and patients co-infected with HIV.
BMS said it will present new data from several daclatasvir-based regimens next month at the annual meeting of The American Association for the Study of Liver Diseases.
“We look forward to bringing daclatasvir to patients in the U.S. and will continue to work closely with the FDA to advance our regulatory application, with the aim of bringing the investigational product to market as quickly as possible,” BMS added.
