October 20, 2016
Gilead Announces SVR12 Rates From Four Phase 3 Studies of a Once-Daily, Fixed-Dose Combination of Sofosbuvir, Velpatasvir and Voxilaprevir in Treatment-Naïve and Treatment-Experienced Genotype 1-6 Chronic HCV-Infected Patients
- If Approved, SOF/VEL/VOX Would Be the First Once-Daily Single Tablet Regimen Available for Salvage for Patients Who Have Failed Prior HCV Therapy with Oral Direct-Acting Antiviral Agent Regimens -
- U.S. NDA Planned for Q4 2016 -
In the POLARIS-1 and POLARIS-4 studies, 445 patients with genotype 1-6 HCV infection who were previously treated with direct-acting antiviral agents (DAAs) received 12 weeks of SOF/VEL/VOX. The POLARIS-1 study enrolled patients who failed prior treatment with an NS5A inhibitor. The POLARIS-4 study enrolled patients who failed prior treatment with a DAA that was not an NS5A inhibitor, most with either an NS5B inhibitor alone (73 percent) or an NS5B inhibitor and an NS3/4A protease inhibitor (25 percent).
In the POLARIS-2 and POLARIS-3 studies, 611 patients who were not previously treated with a DAA received 8 weeks of SOF/VEL/VOX. The POLARIS-2 study enrolled patients with genotype 1-6 HCV infection with or without compensated cirrhosis. The POLARIS-3 study enrolled patients with genotype 3 HCV infection, all of whom had compensated cirrhosis.
The primary endpoint for all studies was SVR12. The intent-to-treat
SVR12 rates observed in the POLARIS studies are summarized in the
following table. Complete results from all four studies will be
presented at The Liver Meeting® 2016 in
41 percent (172/415) had cirrhosis
|1, 2, 3, 4, 5, 6||SOF/VEL/VOX||12 Weeks||
DAA-experienced (No NS5A inhibitor)
46 percent (153/333) had cirrhosis
|1, 2, 3, 4||SOF/VEL/VOX||12 Weeks||
18 percent (174/941) had cirrhosis
|1, 2, 3, 4, 5, 6||SOF/VEL/VOX||8 Weeks||
All had cirrhosis
Patients treated with SOF/VEL/VOX for 12 or eight weeks had similar overall incidence of adverse events compared to placebo-treated or SOF/VEL-treated patients. The most common adverse events among patients who received SOF/VEL/VOX were headache, fatigue, diarrhea and nausea. Among the 1,056 patients who received SOF/VEL/VOX in the four studies, one patient (less than one percent) receiving SOF/VEL/VOX for 12 weeks discontinued due to an adverse event.
“Despite recent advances that have provided high cure rates and
simplified treatment for most HCV patients, those who have failed
previous treatment with direct acting antivirals continue to represent
an unmet medical need. The POLARIS study results demonstrate that
combining three potent antivirals with different mechanisms of action
and high barriers to resistance can provide high cure rates for patients
who have failed other highly effective oral DAA regimens,” said
About the POLARIS Studies
The POLARIS-1 study was a double-blind, placebo-controlled study in 415 genotype 1-6 NS5A inhibitor-experienced patients. The most common prior NS5A inhibitors were ledipasvir (55 percent) and daclatasvir (23 percent).
The open-label POLARIS-4 study evaluated the use of SOF/VEL/VOX or SOF/VEL for 12 weeks in 333 genotype 1-4 HCV-infected patients with prior DAA experience that did not include an NS5A inhibitor. Most patients (85 percent) had prior DAA experience with sofosbuvir.
The open-label POLARIS-2 study evaluated the use of SOF/VEL/VOX for eight weeks or SOF/VEL for 12 weeks in 941 genotype 1-6 DAA-naïve HCV-infected patients, including 18 percent with cirrhosis and 23 percent who had previously failed treatment with an interferon-based regimen.
The open-label POLARIS-3 study randomized patients with genotype 3 HCV infection and cirrhosis to receive SOF/VEL/VOX daily for eight weeks or SOF/VEL for 12 weeks. Of the 219 patients treated, 31 percent had previously failed treatment with an interferon-based regimen.
The POLARIS-1, POLARIS-3 and POLARIS-4 studies met their respective pre-specified primary endpoints for the patients receiving SOF/VEL/VOX. The POLARIS-2 study did not meet its primary endpoint; with a pre-specified 5 percent margin, the SVR12 rate for patients receiving treatment with SOF/VEL/VOX for eight weeks was not statistically non-inferior to the SVR12 rate for patients receiving SOF/VEL for 12 weeks.
The SOF/VEL/VOX fixed-dose combination is an investigational product and
its safety and efficacy have not been established. It has been granted
Breakthrough Therapy designation by the
This press release includes forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995 that are
subject to risks, uncertainties and other factors, including the risk
that future trials involving the SOF/VEL/VOX fixed-dose combination may
have unfavorable results. In addition, Gilead may be unable to file for
U.S. regulatory approval of the SOF/VEL/VOX fixed-dose combination in
For more information on
Gilead Sciences, Inc.
Sung Lee, 650-524-7792
Mark Snyder, 650-522-6167