Clinical Trials

Date: 2015-04-23

Type of information: Presentation of results at a congress

phase: 1,2

Announcement: presentation of results at the 50th Annual Meeting of the European Association for the Study of the Liver (The International Liver CongressTM 2015) in Vienna, Austria

Company: Gilead Sciences (USA - CA)

Product: sofosbuvir, velpatasvir (GS-5816) and GS-9857 (voxilaprevir)

Action mechanism: direct-acting antiviral agent/RNA polymerase (NS5B) inhibitor/ nonstructural protein 5A (NS5A) inhibitor/ NS3/4A protease inhibitor.Sofosbuvir is an oral nucleotide analog inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. This direct-acting agent interferes directly with the HCV life cycle by suppressing viral replication. This nucleotide NS5B polymerase inhibitor is developed by Gilead Sciences. GS-5816 is a NS5A inhibitor. GS-9857 is an investigational NS3/4A protease inhibitor.  

Disease: hepatitis C

Therapeutic area: Infectious diseases

Country:

Trial details:

Latest news:

• • On April 23, 2015, Gilead Sciences announced pre-clinical data and results from Phase 1 and Phase 2 studies supporting the development of an investigational all-oral, pan-genotypic regimen of Sovaldi® (sofosbuvir 400 mg/SOF), the investigational NS5A inhibitor GS-5816 and GS-9857, an investigational NS3/4A protease inhibitor. These data will be presented at the 50th Annual Meeting of the European Association for the Study of the Liver (The International Liver CongressTM 2015) in Vienna, Austria .
• In pre-clinical studies, GS-9857 demonstrated similarly potent antiviral activity against HCV replicons of all tested genotypes (1-6), as well as an improved resistance profile compared to other HCV protease inhibitors (ePoster #P0899). In a healthy volunteer study, GS-9857 demonstrated a favorable pharmacokinetic profile (ePoster #P0861). Data from a three-day monotherapy study also demonstrated that GS-9857 was well-tolerated and achieved median HCV RNA reductions of more than 3 log10 IU/mL for HCV patients with genotypes 1, 2, 3 and 4 at the 100 mg dose (ePoster #P0901). Presented as a late-breaker ePoster (ePoster #LP03), a Phase 2 study of triple-combination therapy with a fixed-dose combination of SOF/GS-5816 plus GS-9857 among genotype 1 patients demonstrated sustained virologic response (SVR12) rates following six weeks of treatment of 93 percent (n=14/15) among treatment-naïve, non-cirrhotic patients, 87 percent (n=13/15) among treatment-naïve, cirrhotic patients, and 67 percent (n=20/30) among those who had failed therapy with two or more direct-acting antiviral agents (DAAs). The four-week regimen resulted in a sub-optimal SVR12 rate of 27 percent (n=4/15).
• SOF/GS-5816 plus GS-9857 was generally well tolerated. There were no Grade 3 or 4 adverse events nor serious adverse events. The most frequent adverse events were nausea (25 percent), headache (24 percent) and fatigue (16 percent). Transient, asymptomatic, elevated lipase (Grade 3 or 4) occurred in four patients (5 percent). Gilead Sciences has recently initiated additional Phase 2 studies to further evaluate the appropriate treatment duration of this regimen for all patients.

 

Is general: Yes