Gilead Sciences announced 144-week data from two phase III studies (Studies 104 and 111) evaluating the safety and efficacy of Genvoya (elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg and tenofovir alafenamide 10mg) for the treatment of HIV-1 infection in treatment-naïve adults. Through week 144, Genvoya demonstrated significantly higher rates of virologic suppression compared to Gilead’s Stribild (elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg and tenofovir disoproxil fumarate 300mg), based on the%age of patients with HIV-1 RNA levels less than 50 copies/mL. Patients receiving Genvoya also demonstrated favorable renal and bone laboratory parameters compared to those treated with Stribild.
Genvoya is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA levels less than 50 copies/mL) on a stable antiretroviral regimen for at least six months with no history of treatment failure and no known resistance to the components of Genvoya. Genvoya has a boxed warning in its product label regarding the risks of lactic acidosis/severe hepatomegaly with steatosis, and post treatment acute exacerbation of hepatitis B.
“As people grow older with HIV, physicians are increasingly looking for highly effective medications that may help address the evolving needs of their patients who face a lifetime of antiretroviral therapy,” said Jose Arribas, M.D., associated professor of Medicine, Hospital La Paz, IdiPAZ, Madrid, Spain and the lead study investigator. “These study results further demonstrate that Genvoya provides durable viral suppression and has a demonstrated safety profile for long-term use by 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 week 144, 84.2% (n=729/866) of patients taking Genvoya and 80% (n=694/867; 95% CI: 0.6% to 7.8%, p=.021) of patients taking Stribild achieved HIV-1 RNA levels less than 50 copies/mL. Additionally, at week 144, 81.1% (n=702/866) of patients taking Genvoya and 75.8% (n=657/867; 95% CI: 1.5 to 9.2%, p=.006) of patients taking Stribild achieved HIV-1 RNA levels less than 20 copies/mL, a secondary endpoint. At week 144, virologic failure was similar between groups (Genvoya, 4.6%; Stribild, 3.9%); the difference in overall results was driven by fewer discontinuations on Genvoya due to adverse events or other reasons not related to efficacy (Genvoya, 11.2%; Stribild, 16.0%). There were statistically significant fewer adverse events leading to discontinuation in the Genvoya arm compared to the Stribild arm (Genvoya, 1.3%; Stribild, 3.3%, p=0.01). The most common drug-related adverse events in both groups were nausea, diarrhea and headache.
A separate analysis investigated the effect of the two regimens on laboratory parameters of kidney, bone and plasma lipid levels. To examine kidney function, specific protein markers of glomerular and tubular function were examined, all of which favored Genvoya. This included a statistically significant difference in the median change in estimated glomerular filtration rate (eGFR) from baseline to week 144 (Genvoya, -1.6 mL/min; Stribild, -7.7 mL/min, p<0.001). There were no cases of renal tubulopathy in the Genvoya arm and four cases in the Stribild arm. No participants on Genvoya had renal-related discontinuations compared to 12 participants in the Stribild arm (p?0.001).
The analysis also found that decreases in bone mineral density (BMD) were significantly less in the Genvoya group versus the Stribild group for both lumbar spine and total hip (spine: Genvoya, -0.92%; Stribild, -2.95%, p<0.001; hip: Genvoya, -0.75%; Stribild, -3.36%, p<0.001). The long-term clinical significance of changes in eGFR and BMD is not known. Finally, patients on Genvoya had statistically higher increases in total, LDL and HDL cholesterol from baseline to week 144 compared to patients on Stribild. There was no significant difference in the total cholesterol-to-HDL ratio at week 144, nor any difference in the rate of initiation of lipid-modifying agents.
Studies 104 and 111, originally planned for 96 weeks and extended to 144 weeks, were randomized, double-blind, controlled phase III trials conducted among 1,733 treatment-naïve adults living with HIV. The primary endpoint of the study was at week 48, in which Genvoya was non-inferior to Stribild. Genvoya was also non-inferior at the secondary endpoint of efficacy at week 96. At study enrollment, 15% of subjects were women, 25% identified themselves as Black or of African descent and 23% had viral loads =100,000 copies/mL. Patients were randomized 1:1 to receive a single tablet regimen of Genvoya or Stribild; randomization included stratification for CD4 count (< 50 cells/µL, 50 to 199 cells/µL, or = 200 cells/µL) and region (U.S. or ex-U.S.) at screening.