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Nov 11, 2013
 |  BioCentury  |  Product Development

Sorting out HCV

Which HCV patients will get Gilead's sofosbuvir or J&J's simeprevir - or both

With two new agents for HCV on the verge of approval, the question becomes which genotype 1 patients will get Gilead Sciences Inc.'s sofosbuvir, Johnson & Johnson's simeprevir - or both together - and which will be "warehoused" to wait for an all-oral, IFN-free solution.

It seems clear sofosbuvir is likely to become the backbone of the first interferon-free regimen in HCV, but only where it was tested in genotypes 2 and 3. In genotype 1 - which is most common in the U.S., Europe and Japan - the options are less straightforward.

On Oct. 24 and Oct. 25, FDA's Antiviral Drugs Advisory Committee voted unanimously to recommend approval of NDAs for both compounds.

Gilead is seeking approval of sofosbuvir, a nucleotide analog HCV NS5B polymerase inhibitor, to treat chronic HCV genotype 1 to 6 infection. The PDUFA date is Dec. 8.

J&J is seeking approval of simeprevir to treat chronic HCV genotype 1 infection in combination with IFN and ribavirin. The pharma's Janssen R&D Ireland unit has ex-Nordic rights to the second-generation HCV NS3/4A protease inhibitor from Medivir AB. The PDUFA date has not been disclosed.

Gilead tested sofosbuvir without IFN only in genotypes 2 and 3. Trials in genotypes 1, 4, 5 and 6 included 12 weeks of IFN and ribavirin. The trials in genotype 1 did not enroll treatment-experienced patients.

J&J tested simeprevir in both treatment-experienced and treatment-naïve patients with HCV genotype 1 infection in combination with 24 or 48 weeks of IFN and ribavirin.

Several doctors who spoke to BioCentury predicted that while sofosbuvir will be given to many patients, some healthier patients will continue to be warehoused for a year or two until an all-oral, IFN-free regimen is approved for genotype 1. These patients will be monitored without receiving any treatment.

For sicker genotype 1 patients, Gilead's sofosbuvir regimen - which uses half the IFN required in current standard of care - is likely to be the preferred choice, even in the untested treatment-experienced population.

FDA reviewers, members of the advisory panel and several doctors who spoke to BioCentury feel the evidence suggesting sofosbuvir will be effective in this population is strong enough to make this "leap of faith."

At this point, J&J's simeprevir likely will not be recommended for about a third of genotype 1a patients in the U.S. and EU with the Q80K polymorphism. In that subgroup, simeprevir appeared ineffective when used with IFN.

However, on Nov. 4, J&J and Gilead presented data from the Phase IIa COSMOS trial showing that an all-oral regimen combining simeprevir plus sofosbuvir can produce robust efficacy in genotype 1 regardless of Q80K mutation status (see "Cosmic Salvation," A11).

Whether and how often doctors will try using sofosbuvir plus simeprevir off label will depend on several factors, including the final label for each product and whether payers will reimburse for the combination.

IFN-free, for some

The U.S. Centers for Disease Control and Prevention estimates there are 3.2 million patients with chronic HCV in the U.S. About 12% are...

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