Gilead seeks FDA's OK for 'breakthrough' ledipasvir/sofosbuvir combo
This article was originally published in Scrip
After gaining the FDA's blessing this past December to market Sovaldi (sofosbuvir), a once-daily oral nucleotide analog polymerase inhibitor, for chronic hepatitis C virus (HCV), Gilead Sciences is seeking to win approval of that medicine as part of a fixed-dose combination with ledipasvir, a NS5A inhibitor.
Sovaldi is specifically approved in the US as part of a combination antiviral regimen to treat patients with HCV genotypes 1, 2, 3 or 4 infection (scripintelligence.com, 7 December 2013).
If the FDA grants its nod to the fixed-dose combination of sofosbuvir and ledipasvir, it would be the first oral treatment regimen for patients with HCV genotype 1 infection in which the need for both interferon and ribavirin is eliminated, Gilead declared.
The sofosbuvir/ledipasvir combo has shown in Phase III testing it may have the potential to cure HCV in genotype 1 patients in as little as eight weeks, said Dr Norbert Bischofberger, the company's executive vice president of R&D and chief scientific officer.
The drug will be used to treat patients either eight or 12 weeks, depending on prior treatment history and whether the patient has cirrhosis.
The FDA has granted its breakthrough therapy designation to the sofosbuvir/ledipasvir combination in the HCV genotype 1 indication.
To obtain the breakthrough therapy designation, which is intended to expedite the regulatory process of a medicine, preliminary clinical evidence must indicate the experimental drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical request (scripintelligence.com, 26 June 2013).
As of 31 January, the FDA's Center for Drug Evaluation and Research has granted 39 of the 127 requests for breakthrough therapy status it has received since July 2012, with regulators denying 64, according to documents posted on the agency's website. The Center for Biologics Evaluation and Research has granted only one of the 22 requests it has received, denying 16 of them so far, with five still pending.
The new drug application (NDA) for the sofosbuvir/ledipasvir combination pill was based on Gilead's Phase III ION-1, ION-2 and ION-3 studies, in which nearly 2,000 genotype 1 HCV patients were randomized to receive the fixed-dose combination, with or without ribavirin, for treatment durations of eight, 12 or 24 weeks.
Trial participants included patients who were treatment-naïve or who had failed previous treatment, including protease inhibitor-based regimens, and also included patients with compensated cirrhosis, Gilead said.
The fact the company was able to submit its NDA ahead of rival AbbVie backs RW Baird analyst Brian Skorney’s thesis Gilead could command 80% of the genotype 1 market.
Gilead said it plans to file in the first quarter of 2014 for regulatory approval of the sofosbuvir/ledipasvir combination in other geographies, including the European Union.
Gilead has submitted an application to the European Medicines Agency (EMA) for accelerated assessment of sofosbuvir/ledipasvir, a designation that is granted to new therapies and medicines of major public health interest.
If accepted, accelerated assessment could shorten the EMA's review time of sofosbuvir/ledipasvir by two months, although it does not guarantee a positive opinion from the Committee for Medicinal Products for Human Use or approval by the European Commission.