Gilead Sciences has announced two-year results from two pivotal Phase 3 studies (Studies 102 and 103) evaluating the company’s single tablet HIV regimen, Stribild (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg), among treatment-naïve patients with HIV-1 infection.
Data show that Stribild was non-inferior after two years of treatment to two standard of care HIV regimens, Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) in Study 102 and a protease-based regimen of ritonavir-boosted atazanavir plus Truvada (emtricitabine and tenofovir disoproxil fumarate) in Study 103. These results were presented in an oral session at the 11th International Congress on Drug Therapy in HIV Infection (HIV11) in Glasgow, U.K.
“In these studies, Stribild demonstrated a robust clinical profile, including sustained efficacy, safety and resistance results over two years of treatment,” says Dr. Jürgen Rockstroh, professor of medicine at the University of Bonn, Germany and a lead investigator for Study 103. “Stribild was also associated with a lower incidence of certain central nervous system side effects compared to Atripla, and had a favorable triglycerides profile versus the atazanavir-based regimen.”
Stribild combines four compounds in one daily tablet: elvitegravir, an integrase inhibitor; cobicistat, a pharmacoenhancing agent; emtricitabine and tenofovir disoproxil fumarate. The regimen was approved by the U.S. Food and Drug Administration on Aug. 27, 2012 for use by treatment-naïve HIV-positive adults based on 48-week results from Studies 102 and 103. A marketing application for Stribild is currently under review in the European Union.
Study 102 found that at 96 weeks of treatment, 84 percent of Stribild patients (n=293/348) and 82 percent of Atripla patients (n=287/352) achieved HIV RNA (viral load) < 50 copies/mL, based on the FDA snapshot algorithm (95 percent CI for the difference: -2.9 to +8.3 percent for Stribild vs. Atripla; predefined criterion for non-inferiority was a lower bound of a two sided 95 percent CI of -12 percent).
Similarly, results from Study 103 show that 83 percent of Stribild patients (n=294/353) and 82 percent of patients receiving the atazanavir-based regimen (n=292/355) achieved HIV RNA < 50 copies/mL, based on the FDA snapshot algorithm (95 percent CI for the difference: -4.5 to +6.7 percent for Stribild vs. the atazanavir-based regimen; predefined criterion for non-inferiority was a lower bound of a two sided 95 percent CI of -12 percent).
In both Studies 102 and 103, rates of discontinuation due to adverse events were similar across all treatment groups (5 percent for Stribild in each study, 7 percent for Atripla and 6 percent for the atazanavir-based regimen). The most common adverse events occurring in at least 10 percent of Stribild patients in Study 102 were diarrhea, nausea, upper respiratory infection, headache, abnormal dreams, fatigue, depression and insomnia; in Study 103, they were diarrhea, nausea, upper respiratory infection, headache, nasopharyngitis, depression, back pain, and fatigue. In Study 102, there were consistently higher reports at each study visit through 96 weeks of abnormal dreams and dizziness in the Atripla arm, with 14 percent and 4 percent of patients experiencing abnormal dreams and dizziness, respectively, on the Atripla arm vs. 8 percent and 1 percent, respectively on the Stribild arm at 96 weeks. Similarly, in Study 103, reports of diarrhea were consistently higher through 96 weeks of treatment on the atazanavir-based arm compared to Stribild, with 4 percent of Stribild patients vs. 9 percent of patients on an atazanavir-based regimen experiencing this problem at 96 weeks.
The frequency of Grade 3-4 adverse events and laboratory abnormalities was also comparable between study regimens. However, in Study 102, patients taking Stribild experienced lower rates of neuropsychiatric side effects (Grades 1-4) through 96 weeks compared to Atripla patients, including abnormal dreams (15 percent for Stribild vs. 28 percent for Atripla), dizziness (8 percent vs. 25 percent) and insomnia (11 percent vs. 16 percent). Patients taking Stribild also experienced lower increases in total cholesterol and LDL (low-density lipoprotein or “bad” cholesterol) compared to Atripla, and in Study 103, experienced significantly smaller increases in triglycerides compared to those taking the atazanavir-based regimen. Additionally, through week 96, reports of Grade 3-4 hyperbilirubinemia were lower in the Stribild arm compared to the atazanavir-based arm (0.6 percent vs. 65 percent).
In September 2012, Stribild was added to U.S. Department of Health and Human Services guidelines as an “alternative” treatment regimen for patients new to HIV therapy. Atripla and ritonavir-boosted atazanavir plus Truvada are both listed as “preferred” first-line regimens in the guidelines. Stribild has a Boxed Warning of lactic acidosis/severe hepatomegaly with steatosis and post treatment acute exacerbation of hepatitis B; see below for important safety information.
Gilead has initiated WAVES, a Phase 3b study evaluating Stribild compared to ritonavir-boosted atazanavir plus Truvada among more than 500 HIV-positive treatment-naïve women. Additional studies examining the efficacy and safety of switching treatment-experienced virologically suppressed patients to Stribild are also underway.
Release Date: November 15, 2012
Filed Under: Drug Discovery