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Press Release

Gilead Presents Results from Phase 3 Studies Evaluating Switching to Descovy® (FTC/TAF)-Based Regimens from Truvada® (FTC/TDF)-Based Regimens

Gilead Sciences
Posted on: 25 Oct 16

FOSTER CITY, Calif.--(BUSINESS WIRE)--Oct. 24, 2016-- Gilead Sciences, Inc. (Nasdaq:GILD) today announced two-year (96-week) data from a Phase 3 study and 48-week data from two Phase 3b studies evaluating the safety and efficacy of switching virologically suppressed HIV-1 infected patients from regimens containing Truvada® (emtricitabine and tenofovir disoproxil fumarate 200mg/300mg; FTC/TDF) to regimens containing Descovy® (emtricitabine and tenofovir alafenamide 200mg/25mg; FTC/TAF). Results demonstrated regimens containing Descovy to be statistically non-inferior to regimens containing Truvada, with improvements in certain renal and bone laboratory parameters among patients receiving Descovy (FTC/TAF)-based regimens. The data were presented in an oral session (Treatment Strategies) at the 2016 HIV Glasgow conference in Glasgow, Scotland, UK.

Descovy is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in patients 12 years of age and older. Descovy should not be used as pre-exposure prophylaxis (PrEP) to reduce the risk of acquiring HIV-1 infection. Descovy has a boxed warning in its product label regarding the risks of lactic acidosis/severe hepatomegaly with steatosis, and post treatment acute exacerbation of hepatitis B. See below for important safety information.

“As people are living longer with HIV, several studies show that patients who switch from regimens containing Truvada to regimens containing Descovy are able to maintain viral suppression while improving renal and bone laboratory markers, which may help address long-term health needs,” said Dr. Chloe Orkin, Consultant, Barts Health NHS Trust, London. “Along with its favorable safety profile, Descovy offers patients and physicians a versatile treatment backbone that can be paired with a range of third agents.”

In Study 1089, 663 virologically suppressed, HIV infected adults were randomized to switch to regimens containing Descovy or continue on regimens containing Truvada, while remaining on the same third agents. At Week 96, virologic suppression (HIV-1 RNA <50 c/mL) was maintained in 89 percent of participants in both groups (difference in percentages: -0.5 percent; 95 percent CI: -5.3 percent to 4.4 percent). Drug-related serious adverse events were rare (Descovy (FTC/TAF)-based regimens, 0 percent; Truvada (FTC/TDF)-based regimens, 0.3 percent) and drug discontinuation due to adverse events was low for both treatment groups (Descovy (FTC/TAF)-based regimens, 2.4 percent; Truvada (FTC/TDF)-based regimens, 1.2 percent). The most commonly reported adverse events included upper respiratory tract infection, diarrhea and nasopharyngitis.

In the same study, the effect of the two regimens on laboratory parameters of kidney and bone health was investigated. Statistically significant differences were observed in mean changes from baseline to Week 96 in bone mineral density (BMD) between patients receiving Descovy (FTC/TAF)-based regimens compared to patients receiving Truvada (FTC/TDF)-based regimens (spine: 2.15 percent vs. -0.17 percent; hip: 1.85 percent vs. -0.33 percent; p<0.05 for both). Additionally, more patients receiving Descovy (FTC/TAF)-based regimens experienced a greater than three percent improvement in BMD from baseline to Week 96, compared with those receiving Truvada (FTC/TDF)-based regimens (spine: 40 percent vs. 18 percent; hip: 29 percent vs. 11 percent; p<0.05 for both).

Differences favoring regimens containing Descovy were also observed in multiple tests of renal laboratory parameters which included median changes from baseline to Week 96 in estimated glomerular filtration rate (eGFR; +10.00 mL/min vs. +4.00 mL/min; p<0.05) and median percent changes in: urine protein-to-creatinine ratio (-26.0 percent vs. +2.7 percent; p<0.05); urine albumin-to-creatinine ratio (+3.4 percent vs. +27.0 percent; p<0.05); urine retinol binding protein-to-creatinine ratio; (-4.1 percent vs. +42.6 percent; p<0.05); and urine beta-2 microglobulin-to-creatinine ratio (-29.7 percent vs. +46.8 percent; p<0.05). There were no cases of Fanconi syndrome. Additionally, there were no cases of proximal renal tubulopathy in the Descovy (FTC/TAF)-based regimens group, and one case in the Truvada (FTC/TDF)-based regimens group through Week 96.

Odefsey® (rilpivirine 25mg/emtricitabine 200mg/tenofovir alafenamide 25mg tablets; RPV/FTC/TAF) is a FTC/TAF-based single tablet regimen indicated as a complete regimen for the treatment of HIV-1 infection in patients 12 years of age and older who have no antiretroviral treatment history and HIV-1 RNA levels ≤100,000 c/mL. Odefsey is also indicated to replace a stable antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 c/mL) for at least six months with no history of treatment failure and no known resistance to the individual components of Odefsey. Odefsey also has a boxed warning in its product label regarding the risks of lactic acidosis/severe hepatomegaly with steatosis, and post treatment acute exacerbation of hepatitis B. See below for important safety information.

In Study 1216, 630 virologically suppressed, HIV infected adults were randomized to switch to Odefsey or to continue on Complera® (rilpivirine 25mg/emtricitabine 200mg/tenofovir disoproxil fumarate 300mg tablets; RPV/FTC/TDF). At Week 48, similar rates of virologic suppression (HIV-1 RNA <50 c/mL) were maintained in both treatment groups (Odefsey, 94 percent; Complera, 94 percent; difference in percentages: −0.3 percent; 95 percent CI: −4.2 percent to +3.7 percent). Drug-related serious adverse events and drug discontinuation due to adverse events were low across both treatment groups (0.1 percent in both). The most commonly reported adverse events included upper respiratory tract infection, diarrhea and nasopharyngitis.

Statistically significant improvements favoring Odefsey were observed from baseline to Week 48 in mean BMD at the hip and spine compared to patients in the Complera group (spine: +1.61 percent vs. +0.08 percent; hip: +1.04 percent vs. -0.25 percent; p<0.001 for both). Additionally, improvements favoring Odefsey were observed in multiple tests of renal laboratory parameters, including median changes in eGFR from baseline to Week 48 (Odefsey, +4.5mL/min; Complera, +0.7 mL/min; p=0.002) and median percent changes in: urine protein-to-creatinine ratio (-18.0 percent vs. +21.5 percent; p<0.001); urine albumin-to-creatinine ratio (-7.8 percent vs. +16.8 percent; p<0.001); urine retinol binding protein-to-creatinine ratio; (-18.8 percent vs. +7.3 percent; p<0.001); and urine beta-2 microglobulin-to-creatinine ratio (-29.0 percent vs. +12.0 percent; p<0.001). No cases of Fanconi syndrome or proximal renal tubulopathy were reported through Week 48.

In Study 1160, 875 virologically suppressed, HIV infected adults were randomized to switch to Odefsey, or to continue on Atripla® (efavirenz 600mg/emtricitabine 200mg/tenofovir disoproxil fumarate 300mg tablets; EFV/FTC/TDF). At Week 48, high rates of virologic suppression (HIV-1 RNA <50 c/mL) were maintained in both treatment groups (Odefsey, 90 percent; Atripla, 92 percent; difference in percentages: -2.0 percent; 95 percent CI: -5.9% to +1.8%) and general safety was similar between the arms. The most commonly reported adverse events included upper respiratory tract infection, nasopharyngitis and cough.

Statistically significant improvements favoring Odefsey were observed from baseline to Week 48 in mean BMD at the hip and spine compared to patients in the Atripla group (spine: +1.65 percent vs. +0.05 percent; hip: +1.28 percent vs. -0.13 percent; p<0.001 for both). A larger percentage of patients receiving Odefsey showed improvements in their osteopenia or osteoporosis at either hip (p=0.004) or spine (p<0.001). Additionally, improvements favoring Odefsey were observed in multiple tests of renal laboratory parameters, demonstrated by changes in total and tubular proteinuria (p<0.001) and percent changes in: urine protein-to-creatinine ratio (-30.0 percent vs. -2.0 percent; p<0.001); urine albumin-to-creatinine ratio (-13.5 percent vs. +12.2 percent; p<0.001); urine retinol binding protein creatinine ratio (-27.6 percent vs. +29.1 percent; p<0.001); urine beta-2-microglobulin creatinine ratio (-41.0 percent vs. +17.1 percent; p<0.001). No cases of Fanconi syndrome or proximal renal tubulopathy were reported through Week 48.

“Results from the studies presented at HIV Glasgow further support the efficacy, as well as the renal and bone safety profile, of regimens containing Descovy as treatment options for appropriate virologically suppressed patients,” said Norbert W. Bischofberger, PhD, Gilead’s Executive Vice President, Research and Development and Chief Scientific Officer. “These data also demonstrate Gilead’s ongoing commitment to developing treatments that may improve health as people grow older with HIV while we continue to search for a cure for the virus.”

Odefsey combines Gilead’s emtricitabine and tenofovir alafenamide with rilpivirine, marketed by Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson. Gilead is responsible for the manufacturing, registration, distribution and commercialization of Odefsey in most countries, while Janssen will distribute it in approximately 18 markets and have co-detailing rights in several key markets, including the United States. The original agreement was established for the development and commercialization of Complera®, marketed as Eviplera® in the EU, and was expanded in 2014 to include Odefsey.

Additional Study Information

Study 1089 is a Phase 3, 96-week randomized, multi-center, double blind, active controlled study of 663 virologically suppressed HIV-1 infected adult patients receiving Truvada (FTC/TDF)-based regimens. The study was designed to evaluate the efficacy and safety of switching from Truvada to Descovy, versus continuing Truvada while remaining on the same third agent. The primary endpoint was virologic success (HIV-1 RNA <50 c/mL) 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. Dosing of Descovy was dependent on the third agent: 200/10mg with ritonavir-boosted protease inhibitors (darunvair, atazanavir and lopinavir) and 200/25mg with unboosted third agents (raltegravir, dolutegravir, nevirapine, efavirenz, rilpivirine and maraviroc). In the United States, only one dose of Descovy (200/25mg) is approved for use with any third agent. 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.

Study 1216 is a Phase 3b, 96-week randomized, double blind, multicenter study among 630 virologically suppressed adults (HIV-1 RNA levels ˂50 copies/mL) on a stable regimen of Complera for ≥ six months. The study was designed to evaluate the efficacy and safety of switching from Complera to Odefsey versus remaining on Complera. The primary endpoint was virologic success (HIV-1 RNA <50 c/mL) at Week 48. The median age of participants was 45 years, with 10 percent female and 19 percent black participants. Inclusion criteria required an eGFR ≥ 50 mL/min, according to the Cockcroft-Gault formula for creatinine clearance.

Study 1160 is a Phase 3b, 96-week randomized, double blind, multicenter study of 875 virologically suppressed adults (HIV-1 RNA levels ˂50 copies/mL) on a stable regimen of Atripla for ≥ six months. The study was designed to evaluate the efficacy and safety of switching from Atripla to Odefsey versus remaining on Atripla. The primary endpoint was virologic success (HIV-1 RNA <50 c/mL) at Week 48. The median age of participants was 49 years, and females comprised 13 percent of the study population. Inclusion criteria required an eGFR ≥ 50 mL/min, according to the Cockcroft-Gault formula for creatinine clearance.

For more information:
www.gilead.com/news/press-releases/2016/10/gilead-presents-results-from-phase-3-studies-evaluating-switching-to-descovy-ftctafbased-regimens-from-truvada-ftctdfbased-regimens

Editor's Details

Mike Wood
PharmiWeb.com
www.pharmiweb.com
editor@pharmiweb.com

Last updated on: 25/10/2016

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