Gilead Announces Phase 3 Results for Genvoya® (Elvitegravir, Cobicistat, Emtricitabine and Tenofovir Alafenamide), an Investigational Once-Daily Single Tablet Regimen for HIV
Gilead Sciences, Inc. (NASDAQ: GILD) today 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.
About Studies 104 and 111
Studies 104 and 111, originally planned for 96 weeks but recently extended to 144 weeks, are randomized, double-blind, controlled Phase 3 trials conducted among 1,733 treatment-naïve adults living with HIV. At study enrollment, 15 percent of subjects were women, 25 percent identified themselves as Black or of African descent and 23 percent had viral loads ≥100,000 copies/mL. Patients were randomized 1:1 to receive an STR of Genvoya or Stribild; randomization included stratification for CD4 count (< 50 cells/µL, 50 to 199 cells/µL, or ≥ 200 cells/µL) and region (United States or ex-United States) at screening. After 48 weeks, high rates of viral suppression were observed in both study arms (Genvoya 92 percent and Stribild 90 percent) and Genvoya met the primary objective of non-inferior efficacy compared to Stribild, defined as the proportion of participants who had HIV-1 RNA < 50 copies/mL using the FDA Snapshot Algorithm.
The studies are ongoing in a blinded fashion. After week 144, patients will continue to take their blinded study drug until treatment assignments have been unblinded, at which point all will be given the option to participate in an open-label rollover extension and receive Genvoya until it is approved for use in the relevant country. Additional information about the studies can be found at www.clinicaltrials.gov.
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.
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 the marketing authorizations for Genvoya and other TAF-based regiments may not be approved by the EMA, FDA or other regulatory authorities, and any marketing approvals, if granted, may have significant limitations on their use. In addition, data from additional TAF studies may be unfavorable. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended June 30, 2015, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
The European SmPCs for Stribild and Viread are available from the EMA website at www.ema.europa.eu.
Genvoya, Stribild and Viread are registered trademarks of Gilead Sciences, Inc., or its related companies.
For more information on Gilead Sciences, please visit the company's website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000
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