Regulatory Decision Summary for STRIBILD

Two pivotal Phase 3b randomized, controlled, open-label studies (Studies GS-US-236-0115 and GS-US-236-0121) were conducted in support of the proposed indication.

Study GS-US-236-0115 was conducted to evaluate the efficacy, safety, and tolerability of switching to Stribild from a regimen consisting of a protease inhibitor + ritonavir + emtricitabine and tenofovir (PI + RTV + FTC/TDF) in virologically suppressed, human immunodeficiency virus-1 (HIV-1) infected subjects. High rates of virologic suppression were maintained through Week 48 both in subjects who switched to Stribild and in subjects who stayed on their baseline regimen (SBR). Results of the primary efficacy analysis using the United States Food and Drug Administration (FDA)-defined snapshot algorithm demonstrated that switching to Stribild was non-inferior to SBR after 48 weeks of treatment (93.8% in the Stribild group and 87.1% in the SBR group had HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48). The rates of virologic failure were low and similar in the two groups. There was no treatment-emergent HIV-1 drug resistance in either group. Continued immunologic benefits of treatment with Stribild and Single Tablet Regimen (STR) were demonstrated by slight increases in CD4 cell counts through Week 48.

Study GS-US-236-0121 was conducted to evaluate the efficacy, safety, and tolerability of switching to Stribild from a regimen consisting of a Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) + FTC/TDF in virologically suppressed, HIV-1 infected subjects. Similar to study GS-US-236-0115, high rates of virologic suppression were maintained through Week 48 both in subjects who switched to Stribild and in subjects who stayed on their baseline NNRTI + FTC/TDF regimen (SBR). Results of the primary efficacy analysis using the FDA-defined snapshot algorithm demonstrated that switching to Stribild was non-inferior to SBR after 48 weeks of treatment (93.4% in the Stribild group and 88.1% in the SBR group had HIV-1 RNA <50 copies/mL at Week 48), with the difference in virologic success rate between groups being 5.9% [95% confidence interval (CI): 0.5% to 12.0%]. The rates of virologic failure were low and similar in the two groups. There was no treatment-emergent HIV-1 drug resistance in either group. Continued immunologic benefits of treatment with Stribild and STR were demonstrated by slight increases in CD4 cell counts through Week 48.

In terms of safety for both studies, Stribild was well tolerated in subjects who switched from their prior regimen, as evidenced by infrequent discontinuations due to adverse events (AEs) and a low incidence of study drug-related serious AEs. One subject in the Stribild group had an AE of acquired Fanconi syndrome, however, this subject had renal laboratory abnormalities suggestive of proximal renal tubulopathy at baseline/screening. As expected in a switch study, the percentages of subjects who had AEs and study drug-related AEs were higher in subjects switching to Stribild compared with subjects staying on their baseline regimen; however, there were no new safety issues identified and the percentages of subjects experiencing any AE in the Stribild group was lower than that seen through Week 48 in treatment-naive subjects in the pivotal Phase 3 studies.

Overall, the benefits of authorizing an indication for the treatment of adults aged 18 years and older infected with HIV-1 with no known mutations to the integrase inhibitor class, tenofovir or emtricitabine outweigh the risks.