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Gilead Presents New Data From the Company's HIV Clinical Development Program and Latest Findings on the Impact of HIV Pre-exposure Prophylaxis (PrEP) at IDWeek 2019
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Results from DISCOVER Trial Provide Bone and Renal Safety Profile Data from Participants who Switched from Truvada for PrEP® to Descovy for PrEP™
Analysis Illustrates the Significant and Independent Impact of High PrEP Use on HIV Diagnoses Rate in Major U.S. Cities -
FOSTER CITY, Calif.--(BUSINESS WIRE)--Oct. 4, 2019-- Gilead Sciences, Inc. (NASDAQ: GILD) today announced important findings from the DISCOVER trial evaluating Descovy®(emtricitabine 200 mg and tenofovir alafenamide 25 mg tablets; F/TAF) for HIV pre-exposure prophylaxis (PrEP), showing significant improvements in key measures of bone and renal safety parameters in a subset of study participants who switched from Truvada®(emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg tablets; F/TDF) for PrEP to Descovy for PrEP™. The company also released the latest data demonstrating that major metropolitan areas in the United States with the highest use of HIV PrEP experienced the greatest decreases in new diagnoses. The data will be presented at the IDWeek 2019 conference being held in Washington, D.C. from October 2-6.
"The results presented at IDWeek reflect Gilead's ongoing commitment to expanding awareness of HIV prevention efforts and the impact of PrEP use in the United States, and continuing to research and develop new prevention options for people at risk for HIV," said Diana Brainard, MD, Senior Vice President, HIV and Emerging Viruses, Gilead Sciences. "The data being shared at this year's meeting underscore the opportunity to reverse the HIV epidemic by supporting and accelerating the use of a broad range of prevention efforts."
Descovy is approved for HIV-1 pre-exposure prophylaxis in at-risk adults and adolescents weighing at least 35 kg who are HIV-negative, excluding individuals at risk from receptive vaginal sex. The indication does not include use of Descovy in individuals at risk of HIV-1 from receptive vaginal sex because effectiveness in this population has not been evaluated.
Descovy and Truvada have Boxed Warnings in their U.S. product labels regarding the risk of drug resistance with use of Descovy for PrEP and Truvada for PrEP® in undiagnosed early HIV infection and the risk of post-treatment acute exacerbation of hepatitis B. See below for Indications and Important Safety Information. Descovy and Truvada do not prevent other sexually transmitted infections or cure HIV or AIDS.
DISCOVER Trial: Renal and Bone Safety Profile Data Among Participants Switching from Truvada to Descovy for HIV Pre-exposure Prophylaxis
Two sub-analyses of data from the DISCOVER trial, a multi-year global Phase 3 clinical study of HIV prevention in 5,387 men and transgender women who have sex with men (MSM, TGW) will be presented. These findings provide new bone and renal safety profile data from a subgroup of 905 study participants (17 percent) who were using Truvada for PrEP at baseline and were randomized 1:1 to either continue Truvada or to switch to Descovy for PrEP.
The first study (oral abstract 1962) reports 48-week renal safety parameters among 465 participants who switched from Truvada for PrEP to Descovy for PrEP after enrolling in the DISCOVER trial, finding statistically significant improvements in key prespecified laboratory measures of kidney function, including urine protein:creatinine (CR) ratio (UPCR), estimated glomerular filtration rate (eGFRCG) and markers of proximal tubular function (β2-microglobulin:Cr ratio [β2M:Cr] and retinol binding protein:Cr ratio [RBP Cr]).
Improvements were statistically significant as early as Week 4 of the trial. At Week 48, eGFRCG increased by 3.9 mL/min from baseline for those randomized to F/TAF and decreased by 0.6 mL/min in those who continued to receive F/TDF (p<0.001). Greater declines in RBP:CR and β2M:Cr were observed among participants randomized to F/TAF compared with those who received F/TDF. Additional renal outcomes data from the 5,387 DISCOVER trial participants through 48 weeks will also be presented, including that study participants randomized to F/TAF for PrEP had fewer study drug-related renal adverse effects (AEs) and fewer discontinuations due to renal AEs compared with study participants randomized to F/TDF. Common adverse reactions (≥2 percent; all grades) in the DISCOVER trial included diarrhea, nausea, headache, fatigue, and abdominal pain.
"These latest findings from the DISCOVER trial continue to support the clinical and public health potential of Descovy for PrEP," said Tony Mills, MD, Assistant Professor of Clinical Medicine, UCLA and Chief Medical Officer, SoCal Men's Medical Group and lead author of the DISCOVER study. "The improvements observed in these important markers of kidney health in the overall study population and in those who switched from Truvada to Descovy point to the potential for Descovy to be a preventive option for appropriate people at risk for HIV who may require longer-term PrEP use, including those who have previously taken Truvada for PrEP."
A second presentation (abstract 1288) reports 48-week data on bone mineral density (BMD) outcomes among a subgroup of DISCOVER trial participants who received additional bone strength evaluations. Of these individuals (n=383), 53 participants were on baseline F/TDF PrEP at enrollment, 26 of whom were randomized to F/TAF. Participants who were randomized to switch to F/TAF experienced statistically significant improvements in BMD of the hip and spine compared with those randomized to continue F/TDF. In addition, participants taking F/TAF for PrEP were significantly less likely to develop osteopenia of the spine. The prevalence of osteopenia among the 2,694 study participants who took F/TAF for PrEP was 0.4 percent. The prevalence of osteopenia among the 2,693 study participants who took F/TDF for PrEP was 0.6 percent. Rates of fracture incidence were similar across the F/TAF and F/TDF groups. Among the subset of participants who were taking F/TDF for PrEP prior to randomization to F/TAF, significant improvements in hip BMD compared with baseline were observed, while spine BMD was unchanged.
"Maintaining bone mineral density is important when considering the potential impact of longer-term PrEP for people at risk for HIV infection," David Alain Wohl, MD, Professor of Medicine, Division of Infectious Diseases, the University of North Carolina at Chapel Hill and lead author of the DISCOVER study. "These results provide valuable insight into the potential impact of Descovy for PrEP on important measures of bone strength in a diverse population over the course of nearly a year."
Increased PrEP Use Associated with Significant Reductions in New HIV Diagnoses in Major U.S. Metropolitan Areas
A new analysis (abstract 1963) demonstrates the significant impact of PrEP for reducing new HIV diagnoses since the approval of the biomedical intervention, finding that between 2012 and 2017 metropolitan statistical areas (MSAs) in the United States with the highest rates of PrEP use experienced the greatest decreases in HIV diagnoses. Importantly, this effect was independent of the impact of treatment as prevention (TasP).
The analysis evaluates U.S. Centers for Disease Control and Prevention (CDC) HIV surveillance data collected between 2012 and 2017 from 105 MSAs, national pharmacy and medical claims databases and proxy data for TasP from HIV-suppressed individuals in 38 states and Washington, D.C. Between 2012 and 2017, the rate of PrEP use among at-risk individuals increased by greater than nine-fold, at an average rate of 2.95 percent per year, and HIV viral suppression increased by 1.34 percent per year during the same period. Overall, from 2012 to 2017, there was a 15.2 percent decline in the total rate of new HIV diagnoses. In MSAs with the highest rates of PrEP use, HIV diagnoses decreased by as much as 4.24 percent per year, whereas in MSAs with the lowest rates of PrEP use, HIV diagnoses decreased by 0.23 percent per year; these declines were statistically significant and independent of TasP. Comparatively, TasP independent of PrEP contributed to a 2.87 percent decline in HIV diagnoses for each percent increase in the proportion of HIV-infected people achieving viral suppression.
Projecting out five years, the analysis suggests that if PrEP utilization among individuals at high risk of HIV could reach 50 percent by 2022 in the MSAs analyzed, a 40.7 percent decline in the rate of new HIV diagnoses is possible.
These data support a multi-prong approach to reducing the number of new HIV diagnoses, combining TasP and PrEP.
Important U.S. Safety Information and Indication for Descovy for PrEP
BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF DESCOVY FOR PrEP IN UNDIAGNOSED EARLY HIV-1 INFECTION and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B
• DESCOVY FOR PrEP must be prescribed only to patients confirmed to be HIV negative immediately prior to initiation and at least every 3 months during use. Drug-resistant HIV-1 variants have been identified with use of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) for HIV-1 PrEP following undetected acute HIV-1 infection. Do not initiate if signs or symptoms of acute HIV-1 infection are present unless HIV-negative status is confirmed
• Severe acute exacerbations of hepatitis B have been reported in patients infected with hepatitis B virus (HBV) who discontinued products containing FTC and/or TDF and may occur with discontinuation of DESCOVY. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients with HBV who discontinue DESCOVY. If appropriate, anti-hepatitis B therapy may be warranted
Contraindication
• DESCOVY FOR PrEP is contraindicated in patients with unknown or positive HIV status
Warnings and precautions
• Comprehensive management to reduce risks:
Use DESCOVY FOR PrEP to reduce the risk of HIV-1 infection as part of a comprehensive strategy that includes adherence to daily dosing and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs)
HIV-1 risk factors: Behavioral, biological, or epidemiologic HIV-1 risk factors may include, but are not limited to: condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high-prevalence area or network
Reduce STI risk: Counsel on the use of STI prevention measures (e.g., consistent and correct condom use, knowledge of partner's HIV-1 viremic status, regular testing for STIs)
Reduce potential for drug resistance:Only prescribe DESCOVY FOR PrEP to patients confirmed to be HIV negative immediately prior to initiation, at least every 3 months while taking DESCOVY, and upon an STI diagnosis. HIV-1 resistance substitutions may emerge in patients with undetected HIV-1 infection who are taking only DESCOVY because DESCOVY alone is not a complete regimen for treating HIV-1
Some HIV tests may not detect acute HIV infection. Prior to initiating DESCOVY FOR PrEP, ask patients about potential recent exposure events. If recent (<1 month) exposures are reported or suspected, or symptoms of acute HIV infection (e.g., fever, fatigue, myalgia, skin rash) are present, confirm HIV-negative status with a test approved by the FDA for use in the diagnosis of acute HIV infection
If HIV-1 infection is suspected or if symptoms of acute infection are present while taking DESCOVY FOR PrEP, convert the DESCOVY FOR PrEP regimen to a complete HIV treatment regimen until HIV-negative status is confirmed by a test approved by the FDA for use in the diagnosis of acute HIV infection
Counsel on adherence: Counsel patients to strictly adhere to daily dosing, as efficacy is strongly correlated with adherence. Some patients, such as adolescents, may benefit from more frequent visits and counseling
• New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. Do not initiate DESCOVY in patients with estimated creatinine clearance (CrCl) <30 mL/min. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue DESCOVY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Monitor renal function in all patients (see Dosage and Administration section)
• Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue use if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations
Adverse reactions
• Most common adverse reactions (≥2%) in the DESCOVY FOR PrEP clinical trial were diarrhea, nausea, headache, fatigue, and abdominal pain
Drug interactions
• Prescribing information: Consult the full Prescribing Information for DESCOVY for more information, warnings, and potentially significant drug interactions, including clinical comments
• Metabolism: Drugs that inhibit P-gp can increase the concentrations of tenofovir alafenamide (TAF), a component of DESCOVY. Drugs that induce P-gp can decrease the concentrations of TAF, which may lead to loss of efficacy
• Drugs affecting renal function: Coadministration of DESCOVY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC and tenofovir and the risk of adverse reactions
Full press release
https://www.gilead.com/news-and-press/press-room/press-releases/2019/10/gilead-presents-new-data-from-the-companys-hiv-clinical-development-program-and-latest-findings-on-the-impact-of-hiv-preexposure-prophylaxis-prep
INDICATION
DESCOVY for PrEP is indicated in at-risk adults and adolescents (≥35 kg) to reduce the risk of sexually acquired HIV-1 infection, excluding individuals at risk from receptive vaginal sex. HIV-1-negative status must be confirmed immediately prior to initiation.
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