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Gilead and AbbVie Seek FDA Approval of Pangenotypic Hepatitis C Treatments

Gilead Sciences and AbbVie both announced this month that they have applied for U.S. Food and Drug Administration approval of new all-oral ribavirin-free combination regimens to treat all genotypes of hepatitis C virus (HCV). Gilead's sofosbuvir/velpatasvir/ voxilaprevir and AbbVie's glecaprevir/pibrentasvir have demonstrated high cure rates in Phase 3 clinical trials.

The advent of direct-acting antiviral agents (DAAs) that can be used in interferon-free regimens has revolutionized treatment for chronic hepatitis C, but there is still room for better options for difficult-to-treat patients including those with HCV genotypes other than 1.

Pangenotypic regimens that work against all genotypes have the potential to be used anywhere in the world without the need for prior genotypic testing.

Gilead's new regimen combines the previously approved HCV nucleotide polymerase inhibitor sofosbuvir (sold alone as Sovaldi), the NS5A inhibitor velpatasvir (sold with sofosbuvir in the Epclusa coformulation), and the investigational HCV protease inhibitor voxilaprevir (formerly GS-9857) in a once-daily coformulation.

As reported at the recent AASLD Liver Meeting, the Phase 3 POLARIS trials showed that sofosbuvir/velpatasvir/voxilaprevir taken for 8 weeks produced an overall sustained virological response (SVR12) rate of 95% for previously untreated people with all HCV genotypes, while a 12-week regimen cured 96%-97% of patients previously treated with other direct-acting antivirals.  8-week regimen cured 96%-99% of the most difficult-to-treat genotype 3 patients with liver cirrhosis.

Gilead said it is requesting an FDA indication for a 12-week course of sofosbuvir/velpatasvir/voxilaprevir as salvage therapy for patients with HCV genotypes 1-6, with or without compensated cirrhosis, who have experienced failure of prior treatment with DAA regimens including NS5A inhibitors.

AbbVie's once-daily "G/P" coformulation contains the investigational pangenotypic HCV NS3/4A protease inhibitor glecaprevir (formerly ABT-493) and the NS5A inhibitor pibrentasvir (formerly ABT-530).

Studies presented at the Liver Meeting showed that glecaprevir/pibrentasvir taken for 8 or 12 weeks cured 98%-99% of non-cirrhotic treatment-naive and treatment-experienced people with HCV genotypes 1, 2, 4, 5, and 6 in the Phase 3 ENDURANCE trials. In the Phase 2 SURVEYOR-2 study the combo taken for 12 or 16 weeks cured at least 96% of treatment-naive and treatment-experienced people with HCV genotype 3 and cirrhosis. Glecaprevir/pibrentasvir also cured almost all hepatitis C patients with advanced kidney disease in the EXPEDITION-4 trial.

The application for glecaprevir/pibrentasvir is supported by data from 8 registrational studies that evaluated more than 2300 patients in 27 countries, according to AbbVie. The company said it plans to submit a marketing authorization application in the European Union in early 2017.

12/27/16

Sources

Gilead Sciences. Gilead Submits New Drug Application to U.S. Food and Drug Administration for the Investigational Single Tablet Regimen Sofosbuvir/Velpatasvir/Voxilaprevir. Press release. December 8, 2016.

AbbVie. AbbVie Submits New Drug Application to U.S. FDA for its Investigational Regimen of Glecaprevir/Pibrentasvir (G/P) for the Treatment of All Major Genotypes of Chronic Hepatitis C. Press release. December 19, 2016.