US clears Gilead's hepatitis C combination drug Harvoni

The FDA announced Friday the approval of Gilead Sciences' Harvoni (ledipasvir/sofosbuvir) to treat adults with chronic hepatitis C virus (HCV) genotype 1 infection. The agency noted that the fixed-dose combination of the NS5A inhibitor ledipasvir and the nucleotide analogue polymerase inhibitor sofosbuvir, which was approved as a single agent in the US last December under the name Sovaldi, is the first oral combination therapy approved for the disease, as well as the first regimen that does not need to be administered with interferon or ribavirin.

Edward Cox, director of the Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research, suggested new HCV therapies are "changing the treatment paradigm" for patients with the disease, noting that "until last year, the only available treatments for hepatitis C virus required administration with interferon and ribavirin." Harvoni is the third drug cleared by the regulator in the past year to treat chronic HCV, following the approval of Johnson & Johnson and Medivir's Olysio (simeprevir) in November 2013, and Sovaldi a month later.

According to Gilead, the FDA's decision was supported by data from the Phase III ION-1, ION-2 and ION-3 studies, which included about 2000 subjects. Patients were randomly assigned to receive Harvoni, administered with or without ribavirin, and tested to see whether they achieved a sustained virologic response at 12 weeks (SVR12) after completing therapy. The ION-1 study consisted of cirrhotic and non-cirrhotic treatment-naive patients, while ION-2 involved patients, with or without cirrhosis, who had failed prior therapy with an interferon-based regimen, and ION-3 enrolled non-cirrhotic treatment-naïve patients. According to Gilead, trial participants in the ribavirin-free arms achieved SVR12 rates ranging from 94 percent to 99 percent.

Principal investigator Nezam Afdhal remarked that "by providing very high cure rates in as little as eight weeks and completely eliminating the need for interferon and ribavirin…Harvoni significantly advances treatment for patients with the most common form of hepatitis C in the US." He added that "for the first time, the vast majority of patients can be cured with a once-daily pill in only eight or 12 weeks."

Harvoni will be priced at $94 500 for a standard 12-week course of treatment, more than the $84 000 cost for Sovaldi that some US lawmakers have already criticised as being too high. In September, Gilead reached licensing agreements with several generic drugmakers to manufacture Sovaldi for distribution in developing countries at a fraction of the US cost. Gregg Alton, executive vice president for corporate and medical affairs at Gilead, noted that Harvoni will cost about $63 000 for patients requiring eight weeks of treatment, with about 35 percent to 40 percent of hepatitis C patients expected to fall into this category. He said insurers could "look at using the eight-week regimen more proactively as a way to reduce cost" over the long term by potentially eliminating the need for more expensive drug treatments later or liver transplants.

Commenting on the Harvoni approval, analyst Michael Yee of RBC Capital Markets said "we expect [Gilead] to continue higher with this green light, as scripts should bounce-back in [the fourth quarter] and 2015 [hepatitis C] estimates are conservative, in our view." For related analysis, see Spotlight On: Four important talking points to watch now that Gilead's Harvoni is approved.

Meanwhile, AbbVie has said the FDA is scheduled to decide by the end of the year whether to approve the interferon-free combination HCV therapy it is co-developing with Enanta Pharmaceuticals, and for which the agency recently granted priority review. Sector & Sovereign analyst Richard Evans suggested AbbVie could offer a 15-percent discount on its three-drug regimen, if approved, to compete with Gilead. However, a spokesperson for AbbVie declined to comment on the drug's pricing, and CEO Richard Gonzalez indicated earlier this year that "we have a product profile that stands up quite nicely in the marketplace, and so [aggressive pricing is] not our strategy going forward." Meanwhile, Troyen Brennan, chief medical officer at CVS Health, said the pharmacy-benefits manager is waiting for the approval of other HCV treatments in order to "negotiate for better prices." For related analysis on pricing, see ViewPoints: Pharma showing a subtle shift in US drug pricing policy? and ViewPoints: CVS report on 'real world' Sovaldi use shows higher dropout rate among naïve patients.

Last month, the European Medicines Agency's Committee for Medicinal Products for Human Use issued a positive opinion regarding Gilead's filing for Harvoni to treat chronic HCV infection in adults. The company also recently applied to have the therapy approved in Japan. Meanwhile, Johnson & Johnson is seeking to market Olysio in combination with Sovaldi, with an FDA decision on the priority review filing expected next month.

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