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Gilead's Sofosbuvir + Velpatasvir Combo Shows Good Results in Phase 3 Trials

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A dual combination of Gilead Sciences' sofosbuvir (Sovaldi) and new pangenotypic HCV NS5A inhibitor velpatasvir (GS-5816) taken for 12 weeks produced cure rates of 95% to 100% for people with hepatitis C genotypes 1 through 6, including patients with compensated liver cirrhosis, in the ASTRAL trials, the company announced this week. People with decompensated cirrhosis, however, did better when they added ribavirin.

Direct-acting antiviral agents used in interferon-free regimens can cure most people with HCV genotype 1, but better options are still needed for other genotypes -- especially hard-to-treat genotype 3. A pangenotypic regimen could simplify treatment worldwide by eliminating the need for genotypic testing prior to therapy.

Below is an edited excerpt from a Gilead press release describing the ASTRAL findings in more detail.

Gilead Announces SVR12 Rates from Four Phase 3 Studies Evaluating a Once-Daily, Fixed-Dose Combination of Sofosbuvir (SOF) and Velpatasvir (VEL) (GS-5816) for the Treatment of All Six Hepatitis C Genotypes

-- If Approved, SOF/VEL Would be the First All-Oral Pan-Genotypic Single Tablet Regimen for Chronic HCV

-- U.S. NDA and European MAA Submissions Planned for Q4 2015

Foster City, Calif. -- September 21, 2015 -- Gilead Sciences, Inc. (Nasdaq:GILD) today announced topline results from four international Phase 3 clinical studies (ASTRAL-1, ASTRAL-2, ASTRAL-3, and ASTRAL-4) evaluating a once-daily, fixed-dose combination of the nucleotide analog polymerase inhibitor sofosbuvir (SOF) with velpatasvir (VEL), an investigational pangenotypic NS5A inhibitor, for the treatment of genotype 1-6 chronic hepatitis C virus (HCV) infection.

In the ASTRAL-1, ASTRAL-2, and ASTRAL-3 studies, 1,035 patients with genotype 1-6 HCV infection received 12 weeks of SOF/VEL. Among these patients, 21 percent had compensated cirrhosis and 28 percent had failed prior treatments. The ASTRAL-4 study randomized 267 patients with decompensated cirrhosis (Child-Pugh class B) to receive 12 weeks of SOF/VEL with or without ribavirin (RBV), or 24 weeks of SOF/VEL. The primary endpoint for all studies was SVR12.

The intent-to-treat SVR12 rates observed in the ASTRAL studies are summarized in the table below. Complete results from all four studies will be presented at future scientific conferences.

[See full press release for table]

Study

 

Population

 

N

 

Treatment

 

Duration

 

SVR12 Rates

ASTRAL-1

 

 

116 patients received placebo (SVR12=0%)

 

Genotypes 1,2,4,5,6

19 percent (121/624)
with cirrhosis

 

624

 

SOF/VEL

 

12 weeks

 

Overall: 99% (618/624)

GT1: 98% (323/328)

GT2: 100% (104/104)

GT4: 100% (116/116)

GT5: 97% (34/35)

GT6: 100% (41/41)

ASTRAL-2

 

Genotype 2

14 percent (38/266)
with cirrhosis

 

134

 

SOF/VEL

 

12 weeks

 

99% (133/134)

   

132

 

SOF+RBV

 

12 weeks

 

94% (124/132)

ASTRAL-3

 

Genotype 3

30 percent (163/552)
with cirrhosis

 

277

 

SOF/VEL

 

12 weeks

 

95% (264/277)

   

275

 

SOF+RBV

 

24 weeks

 

80% (221/275)

ASTRAL-4

 

Genotypes 1-6

All with Child-Pugh class B (decompensated) cirrhosis

 

90

 

SOF/VEL

 

12 weeks

 

83% (75/90)

   

87

 

SOF/VEL+RBV

 

12 weeks

 

94% (82/87)

   

90

 

SOF/VEL

 

24 weeks

 

86% (77/90)

                   

 

Of the 1,035 patients treated with SOF/VEL for 12 weeks in the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,015 (98 percent) achieved the primary efficacy endpoint of SVR12. Of the 20 patients who did not achieve SVR12, 13 patients (1.3 percent) experienced virologic failure and seven did not complete an SVR12 visit (e.g., lost to follow-up). Twelve of the 13 virologic failure patients relapsed (two genotype 1 HCV-infected patients and 10 genotype 3 HCV-infected patients). There was one patient with documented reinfection. No patients with genotype 2, 4, 5 or 6 HCV infection had virologic failure.

Patients treated with SOF/VEL for 12 weeks in these three studies had similar adverse events compared with placebo-treated patients in ASTRAL-1. Two patients (0.2 percent) treated with SOF/VEL for 12 weeks, one each in ASTRAL-1 and ASTRAL-2, discontinued treatment due to adverse events. The most common adverse events were headache, fatigue and nausea.

In ASTRAL-4, patients with Child-Pugh class B cirrhosis receiving SOF/VEL+RBV achieved higher SVR12 rates than patients receiving SOF/VEL for 12 or 24 weeks. Among genotype 1 and 3 patients treated with SOF/VEL+RBV for 12 weeks, the SVR12 rates were 96 percent and 85 percent, respectively.

The most common adverse events across all arms of ASTRAL-4 were fatigue, nausea and headache. Anemia, a common side effect associated with RBV, was reported in 31 percent of patients in the SOF/VEL+RBV arm and in 4 percent and 3 percent of patients treated with SOF/VEL for 12 or 24 weeks, respectively. Treatment emergent serious adverse events occurred in 18 percent of patients and nine patients died. The majority of serious adverse events and deaths were associated with advanced liver disease.

"The ASTRAL study results demonstrate that a 12-week course of therapy with the first fixed-dose combination of two pan-genotypic compounds can provide high cure rates for patients with all HCV genotypes," said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. "We are pleased to have now brought forward our second single tablet regimen for HCV infection that complements Harvoni, our first single tablet regimen approved specifically for patients with genotype 1 infection and which could eliminate the need for HCV genotype testing. We look forward to advancing the regulatory submissions for the SOF/VEL fixed-dose combination."

The U.S. Food and Drug Administration has assigned the SOF/VEL fixed-dose combination a Breakthrough Therapy designation, which is granted to investigational medicines that may offer major advances in treatment over existing options.

The SOF/VEL fixed-dose combination is an investigational product and its safety and efficacy have not yet been established.

About the ASTRAL Studies

The double-blind, placebo-controlled ASTRAL-1 trial enrolled 740 patients with chronic genotype 1, 2, 4, 5 or 6 HCV infection randomized to SOF/VEL or placebo for 12 weeks.

The open-label ASTRAL-2 study evaluated the use of SOF/VEL or SOF+RBV for 12 weeks in 266 genotype 2 HCV-infected patients.

The open-label ASTRAL-3 study evaluated the use of SOF/VEL for 12 weeks or SOF+RBV for 24 weeks in 552 genotype 3 HCV-infected patients.

The ASTRAL-1 study met its primary endpoint of statistical superiority to the pre-specified SVR12 goal of 85 percent (p<0.001). ASTRAL-2 and ASTRAL-3 also met their respective endpoints. In ASTRAL-2, the SVR12 rate among genotype 2 HCV-infected patients receiving SOF/VEL for 12 weeks was statistically superior to the SVR12 rate for patients receiving SOF+RBV for 12 weeks (p=0.018). In ASTRAL-3, the SVR12 rate among genotype 3 HCV-infected patients receiving SOF/VEL for 12 weeks was statistically superior to that of patients treated with SOF+RBV for 24 weeks (p<0.001).

The open-label ASTRAL-4 study evaluated the use of SOF/VEL with or without RBV for 12 weeks and SOF/VEL for 24 weeks in 267 HCV-infected patients with Child-Pugh class B cirrhosis, regardless of genotype.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

U.S. full Prescribing Information for Sovaldi and Harvoni are available at www.gilead.com.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

9/25/15

Source

Gilead Sciences. Gilead Announces SVR12 Rates from Four Phase 3 Studies Evaluating a Once-Daily, Fixed-Dose Combination of Sofosbuvir (SOF) and Velpatasvir (VEL) (GS-5816) for the Treatment of All Six Hepatitis C Genotypes. Press release. September 21, 2015.