February 27, 2015
Gilead Announces Phase 3 Results for Investigational Once-Daily Single Tablet HIV Regimen Containing Tenofovir Alafenamide (TAF)
– First TAF-Based Regimen Found to Be Non-Inferior with Improved Renal and Bone Parameters Compared to Stribild® –
TAF is a novel nucleotide reverse transcriptase inhibitor (NRTI) that has demonstrated high antiviral efficacy at a dose 10 times lower than Gilead’s Viread® (tenofovir disoproxil fumarate, TDF), as well as improved renal and bone laboratory parameters in clinical trials.
“Long-term renal and bone health have been ongoing concerns, especially
as people with HIV live longer and remain on antiretroviral treatment
for greater periods of time,” said
In the combined analyses of Studies 104 and 111, a total of 1,733 treatment-naïve adults with HIV were randomized to receive E/C/F/TAF or Stribild. At 48 weeks, 92.4 percent (n=800/866) of patients taking E/C/F/TAF and 90.4 percent (n=784/867; CI -0.7 percent to +4.7 percent, p=0.13) of patients taking Stribild achieved HIV RNA levels less than 50 copies/mL (Abstract 113LB/Wohl). These analyses 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 (0.9 percent (n=8) for E/C/F/TAF vs. 1.5 percent (n=13) for Stribild), with the most common side effects being diarrhea, nausea, headache and upper respiratory tract infection.
“TAF delivers high levels of tenofovir directly to HIV-infected cells,”
A separate, in-depth analysis investigated the effect of the two regimens on laboratory parameters of kidney, bone and plasma lipid levels (Abstract 143LB/Sax). To examine kidney function, multiple tests of glomerular and tubular function were conducted, all of which statistically favored the E/C/F/TAF regimen. This included a statistically significant difference in the median change in estimated glomerular filtration rate (eGFR) from baseline to week 48, favoring the TAF-based regimen (-6.6 mL/min for E/C/F/TAF vs. -11.2 mL/min for Stribild, p<0.001). The analysis also found that bone mineral density (BMD) was reduced significantly more among patients taking Stribild compared to patients taking E/C/F/TAF (spine: -2.86 vs. -1.30, p<0.001; hip: -2.95 vs. -0.66, p<0.001). Finally, patients on E/C/F/TAF had higher plasma lipid values than patients on Stribild, which appeared to be consistent with the changes seen with other non-TDF based regimens.
“Given its high efficacy and favorable renal and bone safety profile,
Gilead believes E/C/F/TAF represents an important evolution in the
treatment of HIV,” said
Based on initial data from Studies 104 and 111 announced in September
2014, Gilead filed a New Drug Application for E/C/F/TAF with the
In addition to Studies 104 and 111, several other E/C/F/TAF study results were presented this week at CROI. Notably, these include an open-label 48-week study (Study 112) supporting the efficacy and safety of E/C/F/TAF for use among HIV-infected patients with mild-to-moderate renal impairment (CrCL ≥ 30mL/min) (Abstract 795/Pozniak). The study included 242 virologically suppressed patients whose treatment regimens were switched from both TDF- and non-TDF-containing regimens to E/C/F/TAF. The study found that 92 percent of study participants remained virologically suppressed at week 48. There was no significant change in eGFR compared to baseline, and significant improvements were observed in other markers of renal function, including proximal renal tubular laboratory parameters and decreased proteinuria (UPCR >200 mg/g) and albuminuria (UACR≥ 30mg/g). Improvements in BMD (hip and spine) were also observed from baseline to week 48 (median percent change of 0.9 percent and 1.9 percent, respectively). Finally, lipid values among patients taking non-TDF-containing regimens prior to the study decreased, while fasting lipids increased among those who were taking TDF-containing regimens prior to study enrollment.
Twenty-four-week data from another Phase 3 study (Study 106) of
E/C/F/TAF in treatment-naïve adolescents also were presented (Abstract
953/Bennett). Two other studies on emergent resistance in
treatment-naïve adult and adolescent patients taking E/C/F/TAF
(Abstracts 6/Margot and 952/Porter) were presented February 21–22 at the
E/C/F/TAF 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, 43 percent were non-white and 23 percent had viral loads ≥100,000 copies/mL. Patients were randomized 1:1 to receive a single tablet regimen of E/C/F/TAF or Stribild. Baseline median CD4 counts were 404 cells/μL for patients in the E/C/F/TAF arm and 406 cells/μL for those in the Stribild arm. The primary endpoint was Week 48 virologic response by FDA Snapshot Algorithm in a pre-specified analysis of the combined studies.
The primary endpoint was met, as E/C/F/TAF was non-inferior to Stribild, with respect to the proportion of patients having HIV RNA less than 50 copies/mL at Week 48. Median change in CD4 count at Week 48 was 211 cells/µL in the E/C/F/TAF arm vs. 181 cells/µL in the Stribild arm (p=0.024). Virologic failure with resistance occurred in 0.8 percent in the E/C/F/TAF arm and 0.6 percent in the Stribild arm.
There were no reports of proximal renal tubulopathy (including Fanconi Syndrome) in either arm. No single adverse event led to discontinuation of more than one subject on E/C/F/TAF. The most commonly reported adverse events (any grade) were: diarrhea (17 percent vs. 19 percent), nausea (15 percent vs. 17 percent), headache (14 percent vs. 13 percent) and upper respiratory infection (11 percent vs. 13 percent) in the E/C/F/TAF and Stribild arms, respectively.
The studies are ongoing in a blinded fashion. After week 96, 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 E/C/F/TAF. 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,
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
possibility that regulatory authorities may not approve E/C/F/TAF in the
currently anticipated timelines or at all, and marketing approvals, if
granted, may have significant limitations on their use. As a result,
E/C/F/TAF may never be successfully commercialized. 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 Annual Report
on Form 10-K for the year ended
U.S. full Prescribing Information, including BOXED WARNING, for Stribild and Viread is available at www.gilead.com.
Stribild and Viread are registered trademarks of
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.
Gilead Sciences, Inc.
Patrick O’Brien, Investors, 650-522-1936
Ryan McKeel, Media, 650-377-3548