Clinical Trials

Date: 2018-10-03

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the IDWeek 2018 conference

Company: Gilead Sciences (USA - CA)

Product: Biktarvy® (BIC/FTC/TAF - bictegravir (50 mg) and emtricitabine/tenofovir alafenamide (200/25 mg) (FTC/TAF)

Action mechanism:

• integrase inhibitor. Bictegravir is a HIV-1 integrase strand transfer inhibitor (INSTI).
• Biktarvy® is indicated in the U.S. as a complete regimen for the treatment of HIV-1 infection in adults who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those adults who are virologically suppressed (HIV-1 RNA <50 c/mL) on a stable antiretroviral regimen for at least three months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Biktarvy. No dosage adjustment of Biktarvy is required in adult patients with estimated creatinine clearance greater than or equal to 30 mL per minute. Biktarvy carries a Boxed Warning in its U.S. product label regarding the risk of post-treatment acute exacerbation of hepatitis B. See below for Important Safety Information.

Disease: HIV-1 infection in adults

Therapeutic area: Infectious diseases

Country:

Trial details:

Latest news:

• • On October 3, 2018,  Gilead Sciences announced 96-week results from a Phase 3, randomized, double-blinded study (Study 1489) evaluating the safety and efficacy of Biktarvy® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets) for the treatment of HIV-1 infection in treatment-naïve adults. In the ongoing study, Biktarvy® was found to be statistically non-inferior to a regimen of abacavir/dolutegravir/lamivudine (600/50/300mg, ABC/DTG/3TC) through 96 weeks of therapy. The data will be presented during a late-breaking abstract session at the IDWeek 2018 conference in San Francisco.
• In Study 1489, treatment-naïve adults (n=629) were randomized 1:1 in a blinded fashion to receive Biktarvy® (BIC/FTC/TAF) or ABC/DTG/3TC. At Week 96, non-inferiority was maintained from the primary endpoint measurement at Week 48, with 87.9 percent (n=276/314) of patients taking Biktarvy and 89.8 percent (n=283/315) of patients taking ABC/DTG/3TC achieving HIV-1 RNA levels less than 50 copies/mL (difference: -1.9 percent, 95 percent CI: -6.9 percent to 3.1 percent, p=0.45). In the resistance analysis population, none of the study participants randomized to Biktarvy® developed treatment-emergent resistance.
• There were no renal discontinuations and no cases of proximal renal tubulopathy or Fanconi syndrome in the Biktarvy® treatment group. The median change in estimated glomerular filtration rate (eGFR) from baseline to Week 96 was significantly less with Biktarvy compared with ABC/DTG/3TC (-7.8 mL/min vs. -9.6 mL/min, p=0.01). Median changes in proteinuria were similar between both treatment groups. Additionally, the mean percent changes from baseline in spine and hip bone mineral density in the Biktarvy group were similar to ABC/DTG/3TC group (spine: -0.71 vs. -0.22, p=0.14; hip: -1.13 vs. -1.26, p=0.59).
• Biktarvy® was well tolerated through Week 96. Discontinuations due to adverse events were low in both groups (0.0 percent (n=0) for Biktarvy® vs. 2 percent (n=5) for ABC/DTG/3TC). The most commonly reported adverse events (all grades) were nausea (11 percent for Biktarvy® vs. 24 percent for ABC/DTG/3TC), diarrhea (15 percent vs. 16 percent) and headache (13 percent vs. 16 percent).
• Study 1489 is ongoing and will remain randomized and blinded through 144 weeks.
• • On July 24, 2017, Gilead Sciences announced detailed 48-week results from two Phase 3 studies (Studies 1489 and 1490) evaluating the efficacy and safety of a fixed-dose combination of bictegravir (50 mg) (BIC), a novel investigational integrase strand transfer inhibitor (INSTI), and emtricitabine/tenofovir alafenamide (200/25mg) (FTC/TAF), a dual-NRTI backbone, for the treatment of HIV-1 infection in treatment-naïve adults. In the ongoing studies, BIC/FTC/TAF was found to be statistically non-inferior to regimens containing dolutegravir (50mg) (DTG) in combination with a dual-NRTI backbone. The data were presented in two late-breaker sessions [MOAB01 and TUPDB02] at the 9th IAS Conference on HIV Science (IAS 2017) in Paris .
• In Study 1489, a total of 629 treatment-naïve adults with HIV were randomized 1:1 to receive BIC/FTC/TAF or abacavir/dolutegravir/lamivudine (600/50/300mg) ( ABC /DTG/3TC). At Week 48, 92.4 percent (n=290/314) of patients taking BIC/FTC/TAF and 93.0 percent (n=293/315) of patients taking ABC /DTG/3TC achieved the primary endpoint of HIV-1 RNA levels less than 50 copies/mL (difference: -0.6 percent, 95 percent CI: -4.8 percent to 3.6 percent, p=0.78).
• A separate analysis investigated the effect of the two regimens on changes in bone mineral density (BMD) and measures of renal function. Mean percentage changes in BMD from baseline to Week 48 were -0.83 percent for BIC/FTC/TAF vs. -0.60 percent for ABC /DTG/3TC (p=0.39) in lumbar spine, and -0.78 percent for BIC/FTC/TAF vs. -1.02 percent for ABC /DTG/3TC (p=0.23) in total hip. No differences were noted between the treatments in changes from baseline to Week 48 for estimated glomerular filtration rate (eGFR) or proteinuria. Lipid changes were not significantly different between the two arms. No patients randomized to either arm developed treatment-emergent resistance and discontinuations due to adverse events were low in both groups (0.0 percent (n=0) for BIC/FTC/TAF vs. 1.3 percent (n=4) for ABC /DTG/3TC). The most commonly reported adverse events (all grades) were nausea (10 percent for BIC/FTC/TAF vs. 23 percent for ABC /DTG/3TC), diarrhea (13 percent vs. 13 percent) and headache (11 percent vs. 14 percent).
• In Study 1490, a total of 645 treatment-naïve adults with HIV were randomized 1:1 to receive BIC/FTC/TAF or DTG+FTC/TAF. At Week 48, 89.4 percent (n=286/320) of patients taking BIC/FTC/TAF and 92.9 percent (n=302/325) of patients taking DTG+FTC/TAF achieved the primary endpoint of HIV-1 RNA levels less than 50 copies/mL (difference: -3.5 percent, 95 percent CI: -7.9 percent to 1.0 percent, p=0.12). No patients in either treatment arm developed resistance to any of the study drugs. Lipid changes were not significantly different between the two arms, and there were no renal discontinuations or cases of proximal renal tubulopathy. Discontinuations due to adverse events were low in both treatment arms (1.6 percent (n=5) for BIC/FTC/TAF vs. <1.0 percent (n=1) for DTG+FTC/TAF). The most commonly reported adverse events (all grades) were headache (13 percent for BIC/FTC/TAF vs. 12 percent for DTG+FTC/TAF) and diarrhea (12 percent vs. 12 percent).
• In addition to Studies 1489 and 1490, 48-week data from two other ongoing studies evaluating BIC/FTC/TAF among virologically suppressed adult patients (Studies 1844 and 1878) are also part of the regulatory submissions in the U.S. and EU.
• • On May 30, 2017, Gilead Sciences announced that four Phase 3 studies evaluating a fixed-dose combination of bictegravir (50mg), and emtricitabine/tenofovir alafenamide (200/25mg) for the treatment of HIV-1 infection met their primary objectives of non-inferiority. Three of the ongoing studies are designed to explore the efficacy and safety of the combination compared to regimens containing dolutegravir (50mg)  among treatment-naïve patients (Studies 1489 and 1490), and among virologically suppressed patients switching from an existing antiretroviral regimen (Study 1844). A fourth ongoing study in virologically suppressed patients compares switching to BIC/FTC/TAF versus remaining on a suppressive regimen of two nucleoside/nucleotide reverse transcriptase inhibitors and a boosted protease inhibitor (Study 1878).
• Studies 1489 and 1490 are double-blind studies in which treatment-naïve patients (n=600 in each study) were randomized 1:1 to receive BIC/FTC/TAF and abacavir/dolutegravir/lamivudine (600/50/300mg) ( ABC /DTG/3TC) (Study 1489) or DTG+FTC/TAF (Study 1490). The primary endpoint is proportion of patients with HIV-1 RNA levels <50 copies/mL at Week 48, and the lower bound of the 95 percent CI for non-inferiority is 12 percent. The studies remain blinded through 144 weeks.
• In study 1844, patients (n=520) who were virologically suppressed (HIV-1 RNA levels <50 copies/mL) on a regimen of ABC /DTG/3TC or DTG+ABC/3TC were randomized 1:1 to stay on their existing regimen or switch to BIC/FTC/TAF in a blinded manner.
• Study 1878 is an open-label study in which patients (n=520) who were virologically suppressed on a boosted protease inhibitor of darunavir (800mg) or atazanavir (300mg) plus a nucleoside/nucleotide backbone of ABC /3TC or emtricitabine/tenofovir disoproxil fumarate (200/300mg) were randomized 1:1 to either maintain their current regimen or switch to BIC/FTC/TAF.
• The primary endpoint in these studies is the proportion of patients with HIV RNA =50 copies/mL at Week 48, and the lower bound of the 95 percent CI for non-inferiority is 4 percent. Both studies were randomized through 48 weeks, after which point patients continuing in the studies enter an open-label extension receiving BIC/FTC/TAF.
• BIC/FTC/TAF met the definition of non-inferiority in all four studies, with comparable proportions of patients having HIV-1 RNA <50 copies/mL (Studies 1489 and 1490) and HIV-1 RNA =50 copies/mL (Studies 1844 and 1878). In all studies BIC/FTC/TAF was well tolerated and no patients discontinued study medication due to renal events. No patients randomized to the bictegravir or dolutegravir arms developed treatment-emergent resistance. One patient randomized to the protease inhibitor arm in Study 1878 developed an abacavir resistance mutation (L74V). Gilead plans to submit data from these Phase 3 studies for presentations at scientific conferences in 2017.

Is general: Yes