Bictegravir/Emtricitabine/Tenofovir Alafenamide Fumarate

FOSTER CITY, Calif.--( BUSINESS WIRE )--Gilead Sciences, Inc. (Nasdaq: GILD) today announced the presentation of new research data from its innovative HIV treatment portfolio and pipeline, including a broad range of data on investigational and marketed agents with varied dosing frequencies and administration methods. The key findings presented at the International Congress on Drug Therapy in HIV Infection (HIV Glasgow 2024) reflect a transformative portfolio and future-looking pipeline focused on person-centered drug development strategies to address unmet needs in HIV treatment and help end the global epidemic. “ We will not end the epidemic without bringing forward innovative options that help enable all people to achieve long-term success in HIV treatment. The complexities of HIV care require biomedical innovations that put people at the center of the drug development process, with research conducted to help maximize the impact of current treatment options and diligent work to develop more therapies for the future,” said Jared Baeten, MD, PhD, Senior Vice President, Virology Therapeutic Area Head. “ Our contributions to HIV Glasgow highlight our ongoing commitment to a people-first approach to scientific discovery that seeks to expand choices and enhance outcomes for those with HIV.” Long-Term, Observational Data from the BICSTaR Study New outcomes from two datasets derived from the Bictegravir Single Tablet Regimen (BICSTaR) study are consistent with the results observed from multiple Phase 3 clinical trials, which demonstrated the sustained efficacy, safety profile, and high barrier to resistance of Biktarvy. BICSTaR ( NCT03580668 ) is a multinational, prospective, observational, single-arm, non-comparative two-year cohort study, which aims to evaluate the effectiveness, safety, tolerability, and patient-reported outcomes of treatment with Biktarvy in treatment‐naïve (TN) and treatment‐experienced (TE) people with HIV in routine clinical practice. The study enrolled 2,379 people with HIV across 12 countries. Among the people with HIV enrolled in the BICSTaR study, there is a high baseline prevalence of comorbidities. The first presentation reported on four-year outcomes in BICSTaR participants from Canada, France, and Germany. Biktarvy continued to demonstrate high levels of effectiveness and tolerability in clinical practice, with some improvements in patient reported outcomes (PROs) observed in participants who were treatment-naïve (TN). At four years, overall symptoms improved in TN participants and remained stable in TE participants. Similarly, mental component summary scores showed improvements among TN participants and remained stable among TE participants. At 4 years, Biktarvy maintained high rates of virologic suppression (HIV-1 RNA <50 copies/mL), 98% TN and 97% TE, (missing=excluded analysis), respectively. No treatment-emergent resistance to Biktarvy was reported. Discontinuation due to drug-related adverse events occurred in 7% of participants overall, with weight change being the most commonly reported reason at 4% of participants only. Drug-related adverse events (DRAEs) and serious DRAEs were reported in 17%/0% (TN) and 14%/0.3% (TE), respectively. The second BICSTaR analysis focused on self-reported treatment adherence through 24 months in TE participants (n=1,496) who switched to Biktarvy. At both baseline and 24 months, mean adherence score was high, 95% and 97%, respectively. The mean number of reported missed doses over the last 30 days was low (<1). Trajectory analysis showed that most participants had ‘near-perfect’ to moderately high adherence, which was stable over time. In two smaller groups of participants, adherence was initially high but then declined, or was initially low but increased over time, following the switch to Biktarvy. The number of participants with dynamic adherence in the two smaller groups means that findings should be interpreted with caution. Regardless of adherence trajectory, all groups showed high and sustained virologic suppression (HIV-1 RNA <50 copies/mL) with Biktarvy through 24-months (96% overall, missing=excluded analysis), with no treatment-emergent resistance. Long-term success of antiretroviral therapy needs effective regimens that are the least intrusive on the lifestyle of people with HIV. Forgiveness, which is the ability of a given regimen to maintain complete viral suppression despite a documented imperfect adherence, may be considered as an additional feature that can further improve long-term outcomes. In the group of BICSTaR study participants with 4 years of real-world follow-up, Biktarvy continued to demonstrate high levels of effectiveness and tolerability, with some improvements in PROs observed in TN participants. The results underline the importance of patient-reported outcomes as a person-centered approach to HIV research and can help us to better understand the impact on health-related quality of life and specifically, mental health status of people with HIV. This could help inform treatment strategies for these groups. Patterns of Resistance Development with Integrase Strand Transfer Inhibitors The ROSETTA registry aims to collect information on individual cases of virologic failure with integrase strand transfer inhibitor (INSTI)-based regimens, with the goal to correctly inform policy and future use of INSTIs in the treatment of people with HIV. A planned interim analysis presented during a late-breaking oral session included 125 clinical datasets and 124 sequences. 111 cases experienced failure with Dolutegravir (DTG), 10 cases with Bictegravir (BIC), and 4 cases with Cabotegravir (CAB). 19.4% of participants had been previously exposed to earlier INSTIs. Major INSTI resistance mutations were selected in 33 cases (26.6%): 28 cases with DTG failure, 3 with BIC and 2 with CAB. Notably, two of the mutations seen, G118R and R263K, were not observed in cases with earlier INSTI exposure, suggesting different resistance pathways based on past exposure. Additionally, late-breaking data from an analysis of treatment-emergent resistance-associated mutations (TE-RAMs) through a literature review and network meta-analysis was presented comparing the rate of TE-RAMs among oral single-tablet regimens (STRs), including Biktarvy, and injectable cabotegravir+riplivirine (CAB+RPV) in people with HIV who are virologically supressed. No statistically significant differences were identified. However, at 48 weeks, risk of TE-RAMs with Biktarvy was an estimated 78% lower than CAB+RPV injected every two months [RR 0.22 (0.02-2.02 95% CI)] and was estimated to be 46% lower than CAB+RPV injected monthly [RR 0.54 (0.06-5.27 95% CI)]. CAB+RPV injected every two months showed a higher probability of RAMs than all INSTI- and PI-based STRs included in the analysis. In addition, the risk of discontinuing therapy due to AEs at 48 weeks was significantly lower with Biktarvy compared to CAB+RPV injected every month [RR 0.15 (0.03-0.75 95% CI)] and CAB+RPV injected every two months [RR 0.16 (0.04-0.67 95% CI)]. Overall, the analysis found Biktarvy had the highest probability of preventing TE-RAMs, whereas CAB+RPV injected every two months performed similarly to STRs with lower barriers to resistance in relation to the risk of TE-RAMs. Considering the widespread use of INSTI-containing regimens globally, these findings highlight the importance of understanding an individual's treatment history and prior resistance mutation status for treatment management. HIV/HBV Coinfection ALLIANCE ( NCT03547908 ) is an ongoing Phase III study evaluating Biktarvy versus dolutegravir 50 mg (DTG) + emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg, F/TDF, DTG+F/TDF, in adults with HIV-1/HBV co-infection initiating treatment. The ALLIANCE trial is the first randomized clinical trial of TAF- vs TDF-based regimens in treatment naïve adults with HIV/HBV coinfection. Its goal is to evaluate treatment regimens that may effectively suppress both HIV and HBV. Previously reported results demonstrated the efficacy of both antiretroviral regimens. Week 144 outcomes from the open-label extension phase presented at HIV Glasgow report on the longer-term efficacy and safety of the investigational use of Biktarvy in adults with HIV/HBV coinfection initiating treatment. The newly presented data shows that, after 3 years of treatment, Biktarvy maintained high rates of HIV-1 and HBV virologic suppression, defined as HIV RNA <50 copies/ mL and HBV RNA <29 IU/ mL, respectively. At Week 144 Biktarvy maintained high levels of HIV-1 RNA (99.0%) and HBV DNA (80.2%) suppression. Safety findings through three years were consistent with the established profile of Biktarvy. Study drug-related treatment-emergent adverse events(TEAEs) were reported in 32% of participants and most were mild to moderate, with only 1% (n=1) of discontinuations due to TEAEs. These data demonstrate the clinical benefits of Biktarvy for adults with both HIV-1 and HBV initiating antiviral therapy. The use of Biktarvy in individuals with HIV/HBV co-infection is investigational and the safety and efficacy of this use have not been established. Once-Daily Oral Combination of Bictegravir and Lenacapavir ARTISTRY-1 ( NCT05502341 ) is an ongoing, open-label, multicenter Phase 2/3 study being conducted to compare the investigational once-daily combination of bictegravir (BIC), an integrase strand transfer inhibitor, and lenacapavir (LEN), a first-in-class capsid inhibitor, versus current therapy in people with HIV who require a complex treatment regimen to maintain virologic suppression, primarily due to a history of resistance. It is estimated that up to 8% of people with HIV take a complex treatment regimen, defined as two or more pills each day, although single-tablet regimens have become standard of care for HIV treatment due to their simplified dosing. In ARTISTRY-1, 128 participants on a stable baseline regimen for six or more months prior to screening were randomly allocated in a 2:2:1 ratio to receive once-daily oral BIC 75 mg + LEN 25 mg, BIC 75 mg + LEN 50 mg or continue their current stable baseline regimen (n=25). The Week 48 outcomes for BIC + LEN in people with HIV who are virologically suppressed on a complex regimen have been previously presented and demonstrated that all three treatment groups had robust virologic suppression at six months, with consistently low viral loads throughout the study. Week 48 results presented at HIV Glasgow demonstrated parameters measuring lipids and glucose levels generally improved after switching from a baseline regimen to BIC+LEN. At Week 48, fasting lipid parameters generally improved from baseline in both BIC+LEN groups (BIC 75 mg +LEN 25 mg and BIC 75 mg +LEN 50 mg) versus the complex antiretroviral regimen group with a median change in total cholesterol, -12.3% and -8.1%, respectively, versus +1.8%. Fasting glucose levels were comparable, with the BIC+LEN groups at +3 and +2, and -6 in the complex antiretroviral regimen group. Results from a pharmacokinetic (PK) analysis support the use of BIC 75 mg +LEN 50 mg fixed-dose combination (FDC) for Phase 3, which will match the exposure experience of BIC 75mg + LEN 50mg in Phase 2. This dose combination was chosen based on efficacy, safety cumulative PK, and additional consideration of the exposure coverage for potential missed doses. These latest findings support the continued evaluation of a FDC of bictegravir and lenacapavir for use in people with HIV who are virologically suppressed on complex ART regimens. This investigational combination of BIC 75 mg + LEN 50 mg is now being further evaluated as a single-tablet regimen in the Phase 3 portion of the ARTISTRY-1 study as well as in ARTISTRY-2 ( NCT06333808 ), a Phase 3 study comparing the same combination of BIC 75 mg + LEN 50 mg versus Biktarvy in virologically suppressed people with HIV. Novel, Investigational, Weekly Oral Combination HIV Treatment Regimen GS-1720 is a selective integrase strand transfer inhibitor (INSTI) being evaluated as part of a novel, investigational once-weekly antiretroviral agent combination with the goal of providing people with HIV with new long-acting options. Previously presented data demonstrated proof of concept that GS-1720 has a pharmacokinetic profile suitable for weekly dosing. In new outcomes presented at HIV Glasgow, the pharmacokinetics and resistance data of GS-1720 were evaluated in a phase 1b study ( NCT05585307 ). In participants with GS-1720 concentrations at day 11 above 2-fold the inhibitory quotient, robust antiviral activity (≥1.5 log 10 copies/mL reduction in HIV-1 RNA from baseline) was observed. No participant had primary resistance-associated mutations in integrase at screening, and no resistance to the INSTI-class was detected at day 11, across a range of GS-1720 concentrations. These data support the ongoing clinical development of GS-1720 as a component of a novel, investigational, once-weekly oral INSTI/capsid-inhibitor combination regimen with GS-4182 aimed at providing new long-acting treatment options for people with HIV. Long-Acting, Twice-Yearly Regimen of Lenacapavir and Broadly Neutralizing Antibodies (bNAbs) Additional HIV treatment research findings include an oral presentation of a pooled analysis of efficacy and safety outcomes from a Phase 1b study ( NCT04811040 ) evaluating the treatment responses of participants receiving lenacapavir with bNAbs [teropavimab (GS-5423, TAB) + zinlirvimab (GS-2872, ZAB)]. The pooled analysis of Week 26 results is stratified by dose of ZAB (low dose, 10 mg/kg IV; or high dose, 30 mg/kg IV). At Week 26, 21% (n=3) of participants who received LEN + TAB and the low dose of ZAB and 0% (n=0) participants who received LEN +TAB and the high dose of ZAB had an HIV viral load ≥50 copies/mL (per FDA Snapshot). There were no serious adverse events (AEs) related to study drug; the most common AEs were injection site reactions related to subcutaneous LEN administration. Previously presented results showed that high rates of virologic suppression were maintained for six months after one dose of lenacapavir and bNAbs, according to the study screening criteria. These results reinforce the potential of this long-acting combination treatment regimen with twice-yearly dosing and of the continued development of lenacapavir as a foundational agent for potential future long-acting combination HIV treatment options. LEN, TAB and ZAB are being evaluated for treatment compared to standard of care oral ART in an ongoing Phase 2 study ( NCT05729568 ). Bictegravir and lenacapavir in combination are investigational and not approved anywhere globally. Their safety and efficacy have not been established in combination. GS-5423, GS-2872, GS-1720, GS-4182 are investigational compounds, and alone or in combination with lenacapavir, are not approved by the U.S. Food and Drug Administration or any other regulatory authority for any use. Their safety and efficacy are unknown. Please see below for U.S. Indications and Important Safety Information for Biktarvy, including Boxed Warning . There is currently no cure for HIV or AIDS. A bout Lenacapavir Lenacapavir is approved in multiple countries for the treatment of adults with multi-drug resistant HIV in combination with other antiretrovirals. The use of lenacapavir for HIV prevention is investigational and the safety and efficacy of lenacapavir for this use have not been established. The multi-stage mechanism of action of lenacapavir is distinguishable from other currently approved classes of antiviral agents. While most antivirals act on just one stage of viral replication, lenacapavir is designed to inhibit HIV at multiple stages of its lifecycle and has no known cross resistance exhibited in vitro to other existing drug classes. Lenacapavir is being evaluated as a long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead’s HIV prevention and treatment research program. Lenacapavir is being developed as a foundation for potential future HIV therapies with the goal of offering both long-acting oral and injectable options with several dosing frequencies, in combination or as a mono agent, that help address individual needs and preferences of people and communities affected by HIV. About Biktarvy Biktarvy is a complete HIV treatment that combines three powerful medicines to form the smallest 3-drug, integrase strand transfer inhibitor (INSTI)-based single-tablet regimen (STR) available, offering simple once-daily dosing with or without food, with a limited drug interaction potential and a high barrier to resistance. Biktarvy combines the novel, unboosted INSTI bictegravir, F/TAF backbone. Biktarvy is a complete STR and should not be taken with other HIV medicines. U.S. Indication for Biktarvy Biktarvy (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg) is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 14 kg who have no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically-suppressed (HIV-1 RNA <50 copies per mL) on a stable ARV regimen with no known or suspected substitutions associated with resistance to bictegravir or tenofovir. U.S. Important Safety Information for Biktarvy BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF) and may occur with discontinuation of BIKTARVY. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue BIKTARVY. If appropriate, anti-hepatitis B therapy may be warranted. Contraindications Coadministration : Do not use BIKTARVY with dofetilide or rifampin. Warnings and precautions Drug interactions : See Contraindications and Drug Interactions sections. Consider the potential for drug interactions prior to and during BIKTARVY therapy and monitor for adverse reactions. Immune reconstitution syndrome , including the occurrence of autoimmune disorders with variable time to onset, has been reported. New onset or worsening renal impairment : Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with tenofovir alafenamide (TAF)–containing products. Do not initiate BIKTARVY in patients with estimated creatinine clearance (CrCl) <30 mL/min except in virologically suppressed adults <15 mL/min who are receiving chronic hemodialysis. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue BIKTARVY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Renal monitoring: Prior to or when initiating BIKTARVY and during therapy, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients as clinically appropriate. In patients with chronic kidney disease, assess serum phosphorus. Lactic acidosis and severe hepatomegaly with steatosis : Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue BIKTARVY 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 (incidence ≥5%; all grades) in clinical studies through week 144 were diarrhea (6%), nausea (6%), and headache (5%). Drug interactions Prescribing information : Consult the full prescribing information for BIKTARVY for more information on Contraindications, Warnings, and potentially significant drug interactions, including clinical comments. Enzymes/transporters : Drugs that induce P-gp or induce both CYP3A and UGT1A1 can substantially decrease the concentration of components of BIKTARVY. Drugs that inhibit P-gp, BCRP, or inhibit both CYP3A and UGT1A1 may significantly increase the concentrations of components of BIKTARVY. BIKTARVY can increase the concentration of drugs that are substrates of OCT2 or MATE1. Drugs affecting renal function : Coadministration of BIKTARVY 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. Dosage and administration Dosage : Adult and pediatric patients weighing ≥25 kg: 1 tablet containing 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), and 25 mg tenofovir alafenamide (TAF) taken once daily with or without food. Pediatric patients weighing ≥14 kg to <25 kg: 1 tablet containing 30 mg BIC, 120 mg FTC, and 15 mg TAF taken once daily with or without food. For children unable to swallow a whole tablet, the tablet can be split and each part taken separately as long as all parts are ingested within approximately 10 minutes. Renal impairment : For patients weighing ≥25 kg, not recommended in patients with CrCl 15 to <30 mL/min, or <15 mL/min who are not receiving chronic hemodialysis, or <15 mL/min who are receiving chronic hemodialysis and have no antiretroviral treatment history. For patients weighing ≥14 kg to <25 kg, not recommended in patients with CrCl <30 mL/min. Hepatic impairment : Not recommended in patients with severe hepatic impairment. Prior to or when initiating : Test patients for HBV infection. Prior to or when initiating, and during treatment : As clinically appropriate, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, assess serum phosphorus. Pregnancy and lactation Pregnancy : BIKTARVY is recommended in pregnant individuals who are virologically suppressed on a stable ARV regimen with no known substitutions associated with resistance to any of the individual components of BIKTARVY. Lower plasma exposures of BIKTARVY were observed during pregnancy; therefore, viral load should be monitored closely during pregnancy. An Antiretroviral Pregnancy Registry (APR) has been established. Available data from the APR for BIC, FTC, or TAF show no difference in the rates of birth defects compared with a US reference population. Lactation : Individuals infected with HIV-1 should be informed of the potential risks of breastfeeding. About Gilead HIV Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. For more than 35 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention and cure research. Gilead researchers have developed 12 HIV medications , including the first single-tablet regimen to treat HIV, the first antiretroviral for pre-exposure prophylaxis (PrEP) to help reduce new HIV infections, and the first long-acting injectable HIV treatment medication administered twice-yearly. Our advances in medical research have helped to transform HIV into a treatable, preventable, chronic condition for millions of people. Gilead is committed to continued scientific innovation to provide solutions for the evolving needs of people affected by HIV around the world. Through partnerships , collaborations and charitable giving, the company also aims to improve education, expand access and address barriers to care, with the goal of ending the HIV epidemic for everyone, everywhere. Gilead is recognized as one of the leading funders of HIV-related programs in a report released by Funders Concerned About AIDS. Forward Looking Statements 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 Gilead’s ability to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials, including those involving Biktarvy, bictegravir, lenacapavir, teropavimab, zinlirvimab and GS-1720 (such as the ALLIANCE, ARTISTRY, BICSTaR, NCT04811040 and NCT05585307 studies); uncertainties relating to regulatory applications and related filing and approval timelines, including potential applications for indications currently under evaluation, and the risk that any regulatory approvals, if granted, may be subject to significant limitations on use or subject to withdrawal or other adverse actions by the applicable regulatory authority; the possibility that Gilead may make a strategic decision to discontinue development of programs for indications that are currently under evaluation, including bictegravir, lenacapavir, teropavimab, zinlirvimab and GS-1720, and, as a result, these programs may never be successfully commercialized for such indications; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements. U.S. full Prescribing Information for Biktarvy, including Boxed Warning, and U.S. full Prescribing Information for lenacapavir is available at www.gilead.com . Gilead, Biktarvy and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies. For more information about Gilead, please visit the company’s website at www.gilead.com , follow Gilead on X/Twitter ( @Gilead Sciences ) and LinkedIn , or contact Gilead Public Affairs at public_affairs@gilead.com , 1-800-GILEAD-5 or 1-650-574-3000.