Gilead Sciences has submitted its oral nucleotide analogue sofosbuvir for approval in the US as a treatment for chronic hepatitis C virus (HCV) infection.
The filing is a major step forward for Gilead as it tries to develop an all-oral regimen for HCV that does away with the need for injections of interferon alpha, which – while effective – is associated with significant side effects.
The data submitted in the application covers the use of sofosbuvir and ribavirin as an all-oral therapy for patients with genotype 2 and 3 HCV, as well as for sofosbuvir in combination with ribavirin and pegylated interferon alpha for treatment-naïve patients with genotype 1, 4, 5 and 6 HCV.
“Sofosbuvir’s antiviral potency, safety profile and once-daily administration have the potential to improve cure rates by simplifying and shortening therapy for patients with this disease,” commented Gilead’s chief executive John Martin.
The pharma company has completed four phase III trials of sofosbuvir in HCV, showing that the drug in various regimens achieved sustained virologic response (SVR) rates of 65 to 90 per cent, depending on the severity of the infection.
Filings elsewhere in the world, including Europe, will take place in the second quarter of this year, said Gilead in a statement.
If approved, sofosbuvir could become the first drug in the nucleotide polymerase inhibitor or ‘nuke’ category to reach the market, extending the range of oral HCV drugs on the market.
Other orally-active agents – namely the protease inhibitor class represented by Johnson & Johnson/Vertex/Mitsubishi Tanabe’s Incivek/Incivo (telaprevir) and Merck & Co’s Victrelis (boceprevir) – are increasingly being used alongside interferon and ribavirin to boost SVR rates, but new oral agents could be employed to replace the interferon component.
Gilead seems to have developed quite a lead in the race to bring the first nuke to market, particularly as Bristol-Myers Squibb’s own candidate BMS-986094 had to be dropped from development last year because of safety issues.
However, BMS has recently signed a deal with Vertex Pharmaceuticals to partner on a clinical investigating a combination of the BMS candidate daclatasvir and Vertex’ uridine nucleotide analogue VX-135.
Meanwhile, Gilead is also developing a fixed dose combination of sofosbuvir and the NS5A inhibitor ledipasvir, (GS-5885) as an all-oral regimen for genotype 1-infected HCV patients, as well as a combination of the drug with GS-5816 that could improve response rates in hard-to-treat genotype 3 patients.
Analysts have great expectations for sofosbuvir’s commercial prospects, with Barclays recently predicting peak sales of $3.8bn.