An advisory committee to the US Food and Drug Administration (FDA) voted unanimously yesterday that Medivir/Johnson & Johnson’s hepatitis C virus protease inhibitor simeprevir should be approved for marketing.
J&J is trying seeking clearance of simeprevir alongside peginterferon alfa and ribavirin for patients with genotype 1 chronic hepatitis C infection and liver disease who have never received or cannot tolerate interferon-based therapy. The drug was approved in Japan – its first market – under the Sovriad brand name last month.
If the FDA follows the panel’s advice simeprevir will become the third hepatitis C protease inhibitor on the US market after Merck & Co’s Victrelis (boceprevir) and J&J/Vertex Pharma’s Incivek (telaprevir), which were approved in 2011.
Victrelis and Incivek have both had a dramatic impact on the hepatitis C sector, boosting the efficacy of interferon-based treatment regimens and making rapid inroads into the marketplace with sales of $502m and $1.2bn, respectively, in 2012.
Sales of both drugs have started to stall however as a host of new agents coming through development – particularly combinations of directly-acting, oral antivirals that remove the need for injectable interferon therapy – has encouraged patients to hold off starting treatment.
Incivek has also been affected by a boxed warning added to its label in December 2012 linking it to progressive and potentially fatal skin reactions, but Victrelis sales have also started to slip and were down 5 per cent in the first half of the year.
That trend makes it hard to predict the prospects for simeprevir, ahead of all-oral regimens that are due to become available in 2014. However, these are likely to include protease inhibitors alongside other oral agents – such as NS5A polymerase inhibitors and nucleotide polymerase inhibitors – and J&J claims that simeprevir is the most potent compound in its class. Analysts have suggested sales could reach $400m or more within two years.
Meanwhile, J&J bought its own NS5A drug called GSK2336805 from GlaxoSmithKline earlier this month and said it plans to start trials combining it with a non-nucleoside polymerase inhibitor (TMC647055) and simeprevir.
The FDA panel agreed that the data on the efficacy and safety of simeprevir were robust and there is a clear need for additional treatments for hepatitis C. They did point out however that a group of patients with a particular polymorphism (Q80K) did not fare so well on therapy, and the FDA has indicated it would recommend screening of patients for that marker before treatment with the drug.
Other drugs emerging in the protease inhibitor class include Boehringer Ingelheim’s faldaprevir, Merck’s vaniprevir, Bristol-Myers Squibb’s asunaprevir and AbbVie’s ABT 450, which also claim superior viral cure rates and milder side effects than the first-generation drugs.
The FDA panel’s endorsement of simeprevir came ahead of its review later today of Gilead Sciences’ NS5B polymerase inhibitor sofosbuvir, which could become the first all-oral treatment for two less common forms of hepatitis C (genotypes 2 and 3) in combination with ribavirin. Analysts have predicted that sofosbuvir could become a mega blockbuster with sales of $5bn a year or more at peak.