February 23, 2016
Gilead Announces Results From First Study to Evaluate Switching to F/TAF-Based Regimens from Truvada® (F/TDF)-Based Regimens
– Investigational F/TAF-based Regimens Demonstrate High Rates of Virologic Suppression and Improved Renal and Bone Laboratory Parameters Compared to Truvada-based Regimens –
“This study reinforces the benefits we’ve consistently seen in other
trials evaluating TAF-based regimens, including high rates of viral
suppression and improvements in renal and bone lab safety parameters,”
TAF is a novel targeted prodrug of tenofovir that has demonstrated high antiviral efficacy similar to and at a dose less than one-tenth that of Gilead’s Viread® (tenofovir disoproxil fumarate, TDF). TAF has also demonstrated improvement in surrogate laboratory markers of renal and bone safety as compared to TDF in clinical trials in combination with other antiretroviral agents. Data show that because TAF enters cells, including HIV-infected cells, more efficiently than TDF, it can be given at a much lower dose and there is 90 percent less tenofovir in the bloodstream.
In the study, 663 patients were randomized 1:1 in a blinded fashion either to switch to an F/TAF- or continue an F/TDF-based regimen (F/TAF, 333 patients; F/TDF, 330 patients) containing a third antiretroviral agent that was part of the participant's pre-existing treatment regimen. Dosing of F/TAF was dependent on the third agent: 200/10 mg with ritonavir-boosted protease inhibitors (darunvair, atazanavir and lopinavir) and 200/25 mg with unboosted third agents (raltegravir, dolutegravir, nevirapine, efavirenz, rilpivirine and maraviroc).
Through Week 48, similar high rates of virologic suppression (HIV-1 RNA <50 c/mL) were maintained in both treatment groups (F/TAF-based regimens, 94.3 percent; F/TDF-based regimens, 93.0 percent; difference in percentages: 1.3 percent, 95 percent CI: -2.5 percent to +5.1 percent). Drug-related serious adverse events were rare in both groups (F/TAF-based regimens, 0.0 percent; F/TDF-based regimens, 0.3 percent); drug discontinuation due to adverse events also was low across both groups (F/TAF-based regimens, 2.1 percent; F/TDF-based regimens, 0.9 percent). The most commonly reported adverse events in both arms included upper respiratory tract infection, diarrhea, nasopharyngitis, headache and bronchitis.
Statistically significant differences were observed in mean changes from baseline to Week 48 in bone mineral density (BMD) between patients receiving F/TAF-based regimens compared to patients receiving F/TDF-based regimens (hip: F/TAF-based regimens, +1.14 percent; F/TDF-based regimens, -0.15 percent; spine: F/TAF-based regimens, +1.53 percent; F/TDF-based regimens, -0.21 percent, p<0.001 for both). Additionally, more patients receiving F/TAF-based regimens experienced a greater than three percent improvement in BMD from baseline to Week 48, compared with those receiving F/TDF-based regimens (hip: F/TAF, 17 percent; F/TDF, 9 percent, p=0.003; spine: F/TAF, 30 percent; F/TDF, 14 percent, p< 0.001).
Statistically significant differences also were observed in multiple tests of renal function between patients receiving F/TAF-based regimens compared to patients receiving F/TDF-based regimens, which included median changes from baseline to Week 48 in estimated GFR (+8.4 mL/min vs. +2.8 mL/min, p<0.001) and median percent changes in: urine protein-to-creatinine ratio (UPCR) (-14.6 percent vs. +7.7 percent; p<0.001); urine albumin-to-creatinine ratio (UACR) (-7.7 percent vs. +12.3 percent; p<0.001); urine retinol binding protein-to-creatinine ratio (-16.3 percent vs. +18.2 percent; p<0.001) and urine beta-2 microglobulin-to-creatinine ratio (-39.6 percent vs. +22.0 percent; p<0.001). There were no cases of proximal renal tubulopathy in either arm.
“The data presented at CROI this week further support the efficacy,
safety and tolerability advantages of TAF for a range of patients who
face a lifetime of treatment,” said
F/TAF is an investigational product and has not been determined to be safe or efficacious.
About Study 1089
Study 1089 is a 96-week randomized, multi-center, double blind, active controlled study of 663 virologically suppressed HIV-1 infected adult patients receiving F/TDF-based regimens. The study was designed to evaluate the efficacy and safety of switching from F/TDF to F/TAF, versus continuing F/TDF while remaining on the same third agent. The primary endpoint was virologic success at Week 48.
The median age of participants was 49 years, and females comprised 15 percent of the study population. Inclusion criteria required an estimated glomerular filtration rate (eGFR) ≥ 50 mL/min, according to the Cockcroft-Gault formula for creatinine clearance. The median estimated eGFR at study initiation was 100 mL/min. Approximately 46 percent of patients enrolled were treated with a boosted protease inhibitor, 28 percent were treated with an integrase inhibitor and 25 percent were treated with a non-nucleoside reverse transcriptase inhibitor (NNRTI). Additional information about the study can be found at www.clinicaltrials.gov.
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 the
U.S. full prescribing information for Truvada and Viread, including BOXED WARNING, is available at www.gilead.com.
Truvada and Viread are registered trademarks of
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Gilead Sciences, Inc.
Patrick O’Brien, 650-522-1936 (Investors)
Ryan McKeel, 650-377-3548 (Media)