FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD) today announced a pooled analysis of a 48-week open-label extension of two Phase 3 studies (Study 1489 and Study 1490) shows 99% of participants who initiated treatment with Biktarvy® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) maintained an undetectable viral load (HIV-1 RNA <50 copies/mL) through four years of follow-up (Week 192, n=476/480, missing=excluded). In the 48-week open-label extension, there were zero cases of treatment-emergent resistance to any components of Biktarvy in participants treated with Biktarvy. These findings, along with long-term data from Phase 3 studies in virologically suppressed Black Americans and virologically suppressed people living with HIV aged 65 and older, demonstrated Biktarvy sustains efficacy with a high barrier to resistance across a range of people living with HIV, inclusive of their treatment history, gender, race or age. These data were presented at the 11th International AIDS Society (IAS) Conference on HIV Science.
“Four decades after the virus was first reported, it is imperative to commit to driving scientific innovation to meet the needs of people living in today’s world. Globally, the number of older adults with HIV is increasing and communities of color, especially Black adults, continue to be disproportionately affected by HIV while underrepresented in HIV clinical trials,” said Professor Chloe Orkin, MBBCH, FRCP, Lead for HIV Research at Queen Mary University of London. “To help end the global HIV epidemic, effective treatment needs to be acceptable and accessible to everyone. The long-term data reinforce the durability of Biktarvy and highlight its potential role in helping to meet the treatment needs of a diverse group of people living with HIV.”
Gilead presented additional Biktarvy data at IAS 2021, including findings from the BRAAVE 2020 Study, a Phase 3 clinical trial designed with community input to evaluate the specific treatment responses of virologically suppressed adults living with HIV who self-identified as Black or African American following a switch to Biktarvy from a variety of regimens. A total of 495 study participants were randomly allocated and treated in a 2:1 ratio to either switch to open-label Biktarvy for up to 72 weeks (n=330) or to stay on a standard regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a third agent for 24 weeks with a delayed switch to Biktarvy for up to 48 weeks (n=165).
At 72 weeks, 99% of participants (n=246/248, missing=excluded) who switched to Biktarvy at the start of the study maintained an undetectable viral load regardless of age or sex at birth. These results provide further evidence that Biktarvy is an effective and durable treatment option for Black adults who are virologically suppressed, including those with a history of treatment failure or pre-existing resistance.
Gilead also presented long-term data from a Phase 3b open-label trial enrolling people living with HIV aged 65 and older who switched to Biktarvy (n=86) from either Genvoya® (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg, E/C/F/TAF) or a tenofovir disoproxil fumarate (TDF)-based regimen. The analysis showed that 100% of participants (n=68/68, missing=excluded) and 74% of participants (n=64/86) in the snapshot analysis of the Intention to Treat-Exposed (ITT-E) population having HIV-1 RNA <50 copies/mL maintained high rates of virologic suppression at Week 96 with no virologic failures or emergent resistance through 96 weeks. The COVID-19 pandemic impacted in-person visits during the study, with 11 participants unable to be assessed after 84 weeks due to restrictions. There were two participants (2.3%) with Grade 3-4 study drug-related AEs, 11 participants (13%) with Grade 3-4 laboratory abnormalities and three participants (3.5%) with drug-related adverse events (AEs) leading to study drug discontinuation. These results reinforce Biktarvy as an effective and generally well-tolerated treatment option with a high barrier to resistance in the growing population of older people living with HIV.
Results from a Phase 3 study (Study 1844) demonstrated the safety and non-inferior efficacy of switching to Biktarvy in those replacing their existing treatment regimen. In Study 1844, participants (n=563) who were virologically suppressed (HIV-1 RNA <50 copies/mL) on a regimen containing abacavir, dolutegravir, and lamivudine (600/50/300mg) (ABC/DTG/3TC) were randomly allocated and treated in a 1:1 ratio to stay on their existing regimen of ABC/DTG/3TC (n=281) or switch to Biktarvy (n=282) in a blinded manner. The primary endpoint was the proportion of patients with HIV RNA ≥50 copies/mL at Week 48. Study participants were randomly allocated through 48 weeks, after which point participants electing to continue in the study enter an open-label extension receiving Biktarvy. At the point of the last study visit, 98% (n=535/545) of those who switched to Biktarvy maintained virologic suppression for a median duration of two years, including those with pre-existing resistance or who experienced viral “blips.” In participants treated with Biktarvy, there were no cases of treatment failure with resistance to any component of Biktarvy.
“A clinical research program that aims to address the differentiated unmet needs of people living with HIV can help inform long-term treatment strategies and is central to Gilead’s mission to help end the HIV epidemic,” said Frank Duff, Senior Vice President, Virology Therapeutic Area Head, Gilead Sciences. “The four-year data presented at IAS demonstrate the robust and durable efficacy and safety profile of Biktarvy as a treatment option for a diverse range of people living with HIV.”
The use of Biktarvy in individuals with known resistance to the components of Biktarvy is investigational; this use is not approved by the U.S. Food and Drug Administration (FDA), and the safety and efficacy of Biktarvy for this use has not been established. Please see below for the U.S. Indication and Important Safety Information for Biktarvy.
Biktarvy does not cure HIV or AIDS.
About Studies 1489 and 1490
Study 1489 and Study 1490 are Phase 3, double-blind, active-controlled studies. For 144 weeks, treatment-naïve participants were blinded to receive either Biktarvy (n=634) or a dolutegravir-containing triple therapy (n=640). Treatment outcomes were assessed at Week 144 and showed participants in both groups achieved an undetectable viral load with no treatment-emergent resistance. Beyond Week 144, participants were able to receive Biktarvy in an active OLE Phase for up to 96 weeks. Study 1489 and Study 1490 are ongoing.
U.S. Indication for Biktarvy
Biktarvy is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 25 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 /mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of Biktarvy.
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.
- 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.
- Most common adverse reactions (incidence ≥5%; all grades) in clinical studies through Week 144 were diarrhea (6%), nausea (6%), and headache (5%).
- 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: Patients weighing ≥25 kg: 1 tablet taken once daily with or without food.
- Renal impairment: 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.
- 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: There is insufficient human data on the use of Biktarvy during pregnancy. Dolutegravir, another integrase inhibitor, has been associated with neural tube defects. Discuss the benefit-risk of using Biktarvy during pregnancy and conception. An Antiretroviral Pregnancy Registry (APR) has been established. Available data from the APR for FTC shows no difference in the rates of birth defects compared with a U.S. reference population.
- Lactation: Women infected with HIV-1 should be instructed not to breastfeed, due to the potential for HIV-1 transmission.
About Gilead Sciences
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 and cancer.
For more than 30 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention and cure research. Gilead researchers have developed 11 HIV medications, including the first single tablet regimen to treat HIV and the first once-daily oral antiretroviral tablet for pre-exposure prophylaxis (PrEP) to reduce the risk of acquiring HIV infection. These advances in medical research have helped to transform HIV into a 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 and collaborations, 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 operates in more than 35 countries worldwide, with headquarters in Foster City, California.
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 of unfavorable results from ongoing and additional clinical trials involving Biktarvy; and Gilead’s ability to receive FDA and other regulatory approvals for additional indications for Biktarvy, and the risk that any such approvals, if granted, may have significant limitations on its use. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2021, 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 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. Prescribing Information for Biktarvy and Genvoya, including BOXED WARNINGS, are available at www.gilead.com.
Biktarvy, Genvoya, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies.