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|Gilead’s Once-Daily Single Tablet Regimen Stribild Maintains High Viral Suppression Through Two Years of Therapy Among Treatment-Naïve HIV Patients|
-- Pivotal Data from Two Phase 3 Studies Highlight Stribild’s Sustained Efficacy, Safety and Tolerability Profile --
“In these studies, Stribild demonstrated a robust clinical profile, including sustained efficacy, safety and resistance results over two years of treatment,” said Jürgen Rockstroh, MD, Professor of Medicine,
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
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
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
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
Gilead recently 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.
Study 102 is a randomized (1:1), double-blind Phase 3 clinical trial comparing the efficacy, safety and tolerability of Stribild (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) (n=348) versus Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) (n=352) among HIV-infected treatment-naïve adults with HIV RNA levels greater than or equal to 5,000 copies/mL. The primary endpoint of the study is the proportion of patients achieving HIV RNA levels < 50 copies/mL at 48 weeks of treatment, per the
At baseline, patients in the Stribild arm had a median HIV RNA of 4.75 log10 copies/mL and mean CD4 cell count of 391 cells/mm3. Patients in the Atripla arm had a median HIV RNA of 4.78 log10 copies/mL and mean CD4 cell count of 382 cells/mm3. Across both arms, 33 percent of patients had HIV RNA > 100,000 copies/mL, and 13 percent of patients had CD4 counts ≤ 200 cells/mm3.
At 96 weeks, mean increases in CD4 cell counts were 295 cells/mm3 for Stribild patients and 273 cells/mm3 for Atripla patients (p=0.19). Virologic failure rates were 6 percent for Stribild compared to 8 percent for Atripla.
Five percent of Stribild patients and 7 percent of Atripla patients discontinued treatment due to adverse events. The most common adverse events leading to treatment discontinuation among patients taking Stribild were renal events, depression and fatigue. Between 48 and 96 weeks of treatment, two Stribild patients discontinued due to serum creatinine increase without features of proximal renal tubulopathy, and both patients improved after treatment discontinuation.
Median changes from baseline in total cholesterol, HDL (high-density lipoprotein or “good” cholesterol) and LDL at 96 weeks were, respectively, +9, +6 and +9 mg/dL for Stribild and +18, +8 and +16 mg/dL for Atripla (total cholesterol, p<0.001; HDL, p=0.008; LDL, p=0.011). The median change in triglycerides was +4 mg/dL for Stribild and +8 mg/dL for Atripla (p=0.41).
Study 103 is a randomized (1:1), double-blind Phase 3 clinical trial comparing the efficacy, safety and tolerability of Stribild (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) (n=353) versus atazanavir 300 mg boosted by ritonavir 100 mg plus Truvada (emtricitabine and tenofovir disoproxil fumarate) (n=355) among HIV-infected treatment-naïve adults with baseline HIV RNA levels > 5,000 copies/mL. The primary endpoint of the study is the proportion of patients achieving HIV RNA levels < 50 copies/mL at 48 weeks of treatment, per the
At baseline, patients in the Stribild arm had a median HIV RNA of 4.88 log10 copies/mL and mean CD4 cell count of 364 cells/mm3. Patients in the atazanavir-based arm had a median HIV RNA of 4.86 log10 copies/mL and mean CD4 cell count of 375 cells/mm3. Across both arms, 41 percent of patients had HIV RNA > 100,000 copies/mL and 13 percent had CD4 counts ≤ to 200 cells/mm3.
At 96 weeks, patients in both arms experienced similar increases in CD4 cell counts (mean increase of 256 cells/mm3 for Stribild and 261 cells/ mm3 for the atazanavir-based regimen). The virologic failure rate was 7 percent for both treatment regimens. Five percent of Stribild patients and 6 percent of patients on the atazanavir-based regimen discontinued treatment due to adverse events. The most common adverse events leading to treatment discontinuation among patients taking Stribild were renal events, diarrhea, pyrexia, nausea, vomiting and fatigue. Between 48 and 96 weeks of treatment, one Stribild patient and one patient in the atazanavir-based regimen discontinued due to serum creatinine increase without features of proximal renal tubulopathy, and both patients improved after treatment discontinuation.
Ocular icterus (associated with elevated bilirubin levels) was less common among Stribild patients (less than 1 percent) compared to patients taking the atazanavir-based regimen (14 percent).
Median changes from baseline in total cholesterol, HDL and LDL at 96 weeks, were, respectively, +14, +6 and +14 mg/dL for Stribild, and +8, +5 and +11 mg/dL for the atazanavir-based regimen (total cholesterol, p=0.046; HDL, p=0.24; LDL, p=0.32). The median change in triglycerides was +5 mg/dL for Stribild and +16 mg/dL for the atazanavir-based regimen (p=0.012).
Studies 102 and 103 are ongoing in a blinded fashion. After week 192, patients will continue to take their blinded study drug until treatment assignments have been unblinded, at which point all subjects will be given the option to participate in an open-label rollover extension and receive Stribild. Additional information about the study can be found at www.clinicaltrials.gov.
Stribild contains four Gilead compounds in a complete once-daily, single tablet regimen: elvitegravir 150 mg; cobicistat 150 mg; emtricitabine 200 mg; and tenofovir disoproxil fumarate 300 mg. Stribild is indicated in
Elvitegravir is a member of the integrase inhibitor class of antiretroviral compounds. Integrase inhibitors interfere with HIV replication by blocking the ability of the virus to integrate into the genetic material of human cells. Elvitegravir was licensed by Gilead from
Cobicistat is Gilead’s proprietary potent mechanism-based inhibitor of cytochrome P450 3A (CYP3A), an enzyme that metabolizes drugs in the body. Unlike ritonavir, cobicistat acts only as a pharmacoenhancing or “boosting” agent and has no antiviral activity. Gilead submitted an NDA to
Elvitegravir and cobicistat as standalone agents are investigational products and their safety and efficacy have not yet been established.
Important Safety Information about Stribild
BOXED WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B
Warnings and Precautions
Dosage and Administration
Pregnancy and Breastfeeding
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that healthcare providers may not recognize the benefits of starting patients new to therapy on Stribild. As Stribild is used over longer periods of time by many patients with underlying health problems taking numerous other medicines, Gilead may find new issues such as safety, resistance or drug interaction issues, which may require it to provide additional warnings or contraindications on the label or narrow Stribild’s approved indication, each of which could reduce the market acceptance of Stribild. In addition, regulatory authorities including the
U.S. full prescribing information for Stribild is available at www.Stribild.com.
Stribild is a trademark of
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Gilead Sciences, Inc.
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