Gilead Sciences Inc.'s Vemlidy – better known as tenofovir alafenamide, or TAF – won FDA approval as expected for treating adults with chronic hepatitis B virus (HBV) infection with compensated liver disease.
Largely expected to serve as the successor to Viread, Gilead's tenofovir prodrug, Vemlidy (25 mg) was designed to deliver the same antiviral efficacy of Viread (300 mg) at less than 1/10 the dose by more efficiently delivering the active ingredient tenofovir to hepatocytes. That also results in less tenofovir ending up in the bloodstream, with data showing Vemlidy improved renal and bone laboratory safety parameters when compared to Viread.
Approval of Vemlidy was backed by 48-week data from two phase III trials – Studies 108 and 110 – that enrolled a total of 1,298 treatment-naïve and treatment-experienced adults with chronic HBV infection. Study 108 randomized and treated 425 HBeAg-negative patients with either Vemlidy or Viread, and Study 110 randomized and treated 873 HBeAg-positive patients with either Vemlidy or Viread. Both studies met their primary endpoint of noninferiority to Viread based on the percentage of patients with chronic hepatitis B with plasma HBV DNA levels below 29 IU/mL at 48 weeks of therapy.
In addition to improvements in kidney and bone side effects, patients in the Vemlidy arm also showed numerically higher rates of normalization of blood serum alanine aminotransferase, or ALT, levels.
Further data from the Vemlidy program are expected next week during the American Association for the Study of Liver Diseases meeting in Boston.
Foster City, Calif.-based Gilead submitted the NDA for TAF in HBV in January, and approval was largely anticipated by its Nov. 11 PDUFA date. It helped that TAF was already familiar to regulators, having gained approval as part of fixed-dose combinations for use in HIV.
Genvoya, which combines TAF with elvitegravir, cobicistat and emtricitabine, gained approval late last year, while Odefsey, a TAF/emtricitabine combo that adds rilpivirine, was approved by the FDA in March and Descovy, a combination of TAF and emtricitabine, got the nod in April. The three products generated total sales of $654 million for the third quarter, and the rapid market uptake has "reinvigorated HIV franchise growth" for Gilead, noted Cowen and Co. analyst Phil Nadeau. (See BioWorld Today, Nov. 6, 2015, and Nov. 3, 2016.)
Other regulatory filings for Vemlidy in HBV are under review in Europe and Japan. A consensus forecast drawn from four analyst predictions compiled by Cortellis Clinical Trials Intelligence suggests Gilead's sales of the drug could reach $751 million annually by 2018.
Gilead's president and CEO, John Milligan, noted that Vemlidy is the first medicine to treat HBV "in nearly a decade."
Potential competitors, however, are coming fast. Last month, Contravir Pharmaceuticals Inc. reported interim phase IIa data suggesting its candidate, CMX157 (tenofovir exalidex), a tenofovir prodrug, could prove a successful competitor to Viread as well as Vemlidy. The Edison, N.J.-based firm reported that 10 patients treated with its once-daily candidate saw viral load reductions comparable to those achieved with Viread, at a 25-mg dose. (See BioWorld Today, Oct. 14, 2016.)
Contravir also has earlier-stage plans looking at potentially combining CMX157 with its preclinical cyclophilin inhibitor, CRV431.
Another HBV player, meanwhile, has suffered a setback. The FDA put on clinical hold Arrowhead Pharmaceuticals Inc.'s chronic HBV candidate ARC-520, following a toxicology issue linked to nonhuman primate studies. The Pasadena, Calif.-based firm said it expects to hear specifics from the FDA within the next month. (See BioWorld Today, Nov. 10, 2016.)
Similar to Viread, Vemlidy carries a boxed warning on its label regarding the risks of lactic acidosis/severe hepatomegaly with steatosis and post-treatment severe acute exacerbation of hepatitis B.
Shares of Gilead (NASDAQ:GILD) closed Thursday at $77.84, down 63 cents.