Gilead Applies for FDA Approval —By Alan Franciscus

On September 21, 2015 Gilead submitted their Phase 3 data of a once-daily combination of sofosbuvir (polymerase inhibitor) and velpatasvir (NS5A inhibitor) with and without ribavirin to treat genotype 1 through 6 patients to the Food and Drug Administration (FDA) for marketing approval. Patients with decompensated cirrhosis were treated with sofosbuvir plus velpatasvir and ribavirin. The treatment duration was 12 or 24 weeks. The FDA has designated the combination as Breakthrough Therapy. The designation will speed up the drug approval process. This combination will be approved in 2016.

The Phase 3 clinical trials—ASTRAL-1, ASTRAL-2, and ASTRAL-3. There were 1,035 of whom 116 patients received placebo (sugar pills). There were 267 people in the ASTRAL-4 trial—this trial included the patients with genotypes 1 through 6 with decompensated cirrhosis. There was not a breakdown by genotype. The breakdown is listed below.

ASTRAL-1 Trial included 121 (19%) patients – with cirrhosis: The overall cure rates were 99% (618 of 624 pts) – all patients received sofosbuvir plus velpatasvir
Genotype 1
Genotype 2
Genotype 4
Genotype 5
Genotype 6
98% cured
(323 of 328 pts)
100% cured
(104 of 104 pts)
100% cured
(116 of 116 pts)
97% cured
(34 of 35 pts)
100% cured
(41 of 41pts)

ASTRAL-2 Trial included 266 genotype 2 patients – (14%) with cirrhosis: 
Sofosbuvir plus velpatasvir – 12 weeks
99% cured (133 of 134 pts)
Sofosbuvir plus ribavirin – 12 weeks
94% cured (124 of 132 pts)

ASTRAL-3 Trial included 552 genotype 3 patients – 30% with cirrhosis:
Sofosbuvir plus velpatasvir – 12 weeks
95% cured (264 of 277 pts)
Sofosbuvir plus ribavirin – 24 weeks
80% cured (221 of 275 pts)

Astral – 4 Trial included 267 genotype 1 through 6 patients with decompensated cirrhotic patients (Child-Pugh class B) patients. 
Sofosbuvir plus velpatasvir – 12 weeks
83% (75 of 90 pts)
Sofosbuvir/velpatasvir plus ribavirin – 12 weeks
94% (82 of 87 pts)
Sofosbuvir plus velpatasvir – 24 weeks
86% (77 of 90 pts)

The most common side effects were headache, fatigue and nausea. Thirty-one percent of patients in the arms that contained ribavirin experienced anemia. Anemia was also reported in 3% of the patients in the arms that contained sofosbuvir and velpatasvir, but not ribavirin. According to the press release, the majority of the serious side effects (18%) and deaths (9) were associated in people with advanced liver disease.

Note: There was no information given about prior treatment experience in the genotype 3 patients with cirrhosis—people with hepatitis that are in need of better treatment options. This information will be given at The Liver Conference.

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