Gilead Sciences has announced 96-week results from two Phase 3 studies (Studies 104 and 111) evaluating its investigational once-daily single tablet regimen (STR), Genvoya®(elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg and tenofovir alafenamide 10 mg or E/C/F/TAF), for the treatment of HIV-1 infection in treatment-naïve adults. Genvoya was found to be statistically non-inferior to Stribild® (elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg or E/C/F/TDF), based on percentages of patients with HIV-1 RNA levels less than 50 copies/mL. Patients receiving Genvoya also had improved renal and bone laboratory parameters compared to those treated with Stribild. The data were presented at the 15th European AIDS Conference (EACS) in Barcelona (session: BD 01).
TAF is a novel, investigational nucleotide reverse transcriptase inhibitor (NRTI) that has demonstrated high antiviral efficacy at a dose less than one-tenth that of Gilead’s Viread® (TDF), as well as improvement in surrogate laboratory markers of renal and bone safety as compared to TDF in clinical trials in combination with other antiretroviral agents.
“As people live longer with HIV and remain on antiretroviral treatments throughout their lives, there is a need for new regimen options for people with HIV- and treatment-related comorbidities,” said José R. Arribas, Associated Professor of Medicine, Hospital La Paz, IdiPAZ, Madrid, Spain. “The data presented this week show Genvoya has the potential to help preserve the health of a range of appropriate HIV patients.”
In the combined analysis of Studies 104 and 111, a total of 1,733 treatment-naïve adults with HIV were randomized to receive either Genvoya or Stribild. At 96 weeks, 86.6 percent (n=750/866) of patients taking Genvoya and 85.2 percent (n=739/867; CI -1.8 percent to +4.8 percent, p=0.36) of patients taking Stribild achieved HIV-1 RNA levels less than 50 copies/mL. The analysis found that the rate of virologic success between the two regimens was similar across patient subgroups (age, gender, race, baseline HIV-1 RNA level and baseline CD4 count). Discontinuations due to adverse events were low in both treatment arms (1.2 percent (n=10) for Genvoya vs. 2.3 percent (n=20) for Stribild). The most common side effects were headache, diarrhea and nausea.
The combined analysis investigated the effect of the two regimens on kidney, bone and lipid laboratory parameters over the 96-week period. To examine kidney function, multiple laboratory tests of renal and tubular function were conducted, all of which statistically favored Genvoya. This included a statistically significant difference in the median change in estimated glomerular filtration rate (eGFR) from baseline to week 96, favoring Genvoya (-2.0 mL/min for Genvoya vs. -7.5 mL/min for Stribild, p<0.001). Patients taking Genvoya had smaller declines in bone mineral density (BMD) compared to patients taking Stribild, as assessed by DXA (spine: -0.96 vs. -2.79, p<0.001; hip: -0.67 vs. -3.28, p<0.001). Patients on Genvoya had statistically higher increases in total, LDL and HDL cholesterol from baseline than patients on Stribild, while there was no significant difference between the arms in the total cholesterol to HDL ratio. Finally, there were no reports of proximal renal tubulopathy (including Fanconi Syndrome) in the Genvoya arm while there were two cases in the Stribild arm.
“The two-year data presented this week further support the long-term utility of Genvoya, given the sustained viral suppression and continued improvements in renal and bone safety markers,” said Norbert W. Bischofberger, PhD, Gilead’s Executive Vice President, Research and Development and Chief Scientific Officer. “Pending regulatory approvals in the U.S. and Europe, we look forward to bringing Genvoya and our other next-generation TAF-based therapies to patients as quickly as possible.”
Additional investigational Phase 3 study results for Genvoya that will be presented at EACS include a 48-week analysis of Study 109 in adult patients switching from boosted atazanavir (ATV) plus F/TDF to Genvoya (session: PS10), sub-analyses of Studies 104 and 111 examining Genvoya vs. Stribild among treatment-naïve adult women at 48 weeks (poster: PE7/13) and drug resistance through 48 weeks in treatment-naive subjects receiving Genvoya (poster: PE9/5).
On September 24, 2015, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion on the company’s Marketing Authorization Application for Genvoya. The CHMP’s recommendation will now be reviewed by the European Commission, which has the authority to approve medicines for use in the 28 countries of the European Union. Based on initial data from Studies 104 and 111, announced in September 2014, Gilead filed a New Drug Application for Genvoya with the U.S. Food and Drug Administration (FDA) on November 5, 2014. Under the Prescription Drug User Fee Act, the agency has set a target action date of November 5, 2015.
Genvoya is an investigational product and has not been determined to be safe or efficacious.