GILD Gilead Sciences Inc

– New 5-Year Clinical and Real-World Data Reinforce Biktarvy® as a Long-Term Treatment Option for a Diverse Range of People with HIV, Including Those with Comorbidities –

– Investigational, Once-Daily, Once-Weekly and Twice-Yearly Dosing Frequencies Across Administration Methods Aim to Expand Options, Advance Public Health and Help Address Unmet Needs in HIV Treatment –

Gilead Sciences, Inc. (Nasdaq: GILD) today announced the presentation of key data from its innovative HIV treatment portfolio and research pipeline, including a broad range of investigational and marketed agents with varied dosing frequencies and administration methods. The findings presented at the 25th International AIDS Conference (AIDS 2024) reflect a portfolio and future-looking pipeline focused on person-centered drug development strategies to help address unmet needs in HIV treatment.

"People are at the center of all we do in HIV treatment research at Gilead. We strive to support people with HIV throughout their lifetimes, with research to maximize the impact of current treatment options and diligent work to develop treatment options for the future,” said Jared Baeten, MD, PhD, Senior Vice President, Virology Therapeutic Area Head. “Durable viral suppression is the primary goal of HIV care and treatment, resulting in longer, healthier lives for people with HIV and, when undetectable, eliminating the risk of transmitting the virus to partners. Long-term success includes rigorous innovation so that each person can be on the right treatment for them that will support long-term treatment outcomes.”

Five-Year Data Shows Biktarvy Maintains High Rates of Virologic Suppression in Hispanic/Latine People with HIV

New research presented at AIDS 2024 demonstrated the durability and long-term safety profile of Biktarvy® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) in Hispanic/Latine people with HIV, who often experience disparities in health outcomes and are often under-represented in HIV clinical trials. Specifically, results of the subgroup analysis showed that at five years, Biktarvy treatment was generally well tolerated and maintained high virologic suppression. Based on a Missing=Excluded (M=E) analysis, 100% of the Hispanic/Latine participants and 98.1% of the non-Hispanic/Latine participants maintaining undetectable status and a viral load of less than 50 copies/mL at Week 240. No treatment-emergent resistance was detected. This analysis evaluating Biktarvy includes a pooled analysis of two Phase 3 randomized studies (Study 1489 and Study 1490) in Hispanic/Latine people with HIV who were initiating treatment with Biktarvy in the 144-week randomization phase and in the 96-week open-label extension phase.

“HIV affects some communities more significantly and deeply than others, and the Hispanic/Latine community specifically needs the results of long-term studies that examine differences in outcomes and treatment nuances," said Santiago Moreno Guillen, MD, Head of the Infectious Diseases Service at the Ramón y Cajal Hospital in Madrid. "These long-term findings will help us determine the best treatment approach and can make a very big difference in the lives of our community. The robust efficacy shown in Hispanic/Latine participants at five years provides remarkable long-term insight and reinforces the role of Biktarvy as an effective treatment option for Hispanic/Latine people living HIV."

Biktarvy was generally well tolerated in both groups, with similar metabolic and safety outcomes and few TEAEs leading to treatment discontinuation. The most common study drug-related TEAEs in Hispanic/Latine or non-Hispanic/Latine participants, respectively, were diarrhea (2%, 6%), headache (5%, 5%), and nausea (3%, 5%).

Switch Data From Real-World BICSTaR Study Shows Biktarvy Maintains High Levels of Virologic Suppression in Older Adults With Comorbidities

Additional new long-term data from the Bictegravir Single Tablet Regimen (BICSTaR) study evaluated the effectiveness and safety of Biktarvy in people aged 50 years and older with HIV who switched to the single-tablet regimen and currently have or have had at least one additional medical condition. Outcomes at two years included viral suppression rates, treatment-emergent resistance, drug-drug interactions and patient satisfaction (survey conducted 12 months after switching).

BICSTaR (NCT03580668) is an ongoing, multinational, observational single-arm, non-comparative real-world cohort study, which aims to evaluate the effectiveness, safety, tolerability, and patient-reported outcomes of treatment with Biktarvy in treatment‐naïve and treatment‐experienced people with HIV. Among the people with HIV enrolled in the BICSTaR study, there is a high baseline prevalence of comorbidities.

Results showed high rates of effectiveness two years after switching to Biktarvy, with 96% (315/328) of individuals maintaining an undetectable viral load of less than 50 copies/mL based on a Missing=Excluded (M=E) analysis. Viral suppression rates at 24 months were similar regardless of age, sex and race at the time of the switch, ranging from 93-100% across subgroups. Patient-reported treatment satisfaction based on the HIVSTQc score increased through one year. No treatment-emergent resistance to Biktarvy was observed throughout the 24 months after switching.

The BICSTaR population included 401 people with a median age of 56 years, with 86% male, 81% White and 18% aged 65 years or older. Most common baseline comorbidities were cardiovascular (48%), metabolism and nutrition disorders (48%), infections (34%), and psychiatric disorders (34%), and 22% were taking five or more comedications. Switching to Biktarvy was generally well tolerated. Treatment-related adverse events (TRAEs) occurred in 13% (54/401) of patients, with serious TRAEs occurring in 0.2% (1/401). Discontinuation due to TRAEs occurred in 7% (27/401) of patients. Those who switched to Biktarvy remained clinically stable, with no significant worsening in lipid, kidney or liver measures.

The data presented at AIDS 2024 complement those observed in multiple Phase 3 clinical trials, which demonstrated the sustained efficacy, safety profile, and high barrier to resistance of Biktarvy.

Once-Daily Oral Combination of Bictegravir and Lenacapavir Demonstrates Sustained Viral Suppression

ARTISTRY-1 (NCT05502341) is an ongoing, open-label, multicenter Phase 2/3 study being conducted to compare the investigational once-daily combination of bictegravir, an integrase strand transfer inhibitor, and lenacapavir, 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 and potential benefits for adherence.

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 bictegravir 75 mg + lenacapavir 25 mg, bictegravir 75 mg + lenacapavir 50 mg or continue their current stable baseline regimen (n=25). The 24-week primary efficacy and safety outcomes for bictegravir + lenacapavir 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 outcomes presented at AIDS 2024 show that 90% of participants (n=52) treated with once-daily oral bictegravir 75 mg + lenacapavir 50 mg and 92% of participants (n=51) treated with once-daily oral bictegravir 75mg + lenacapavir 25 mg were virologically suppressed (HIV viral load <50 copies/mL per FDA Snapshot). Changes in CD4 counts were comparable among groups. In the higher lenacapavir dose group, only one participant had a viral load above the threshold, which was later suppressed after changing the regimen. In the lower lenacapavir dose group, two participants had a viral load above the threshold, with both individuals later suppressed without regimen change.

Bictegravir + lenacapavir was generally well tolerated, with few treatment-emergent adverse events (TEAEs) leading to premature treatment discontinuation. Up to Week 48, the most common TEAEs in the higher dose bictegravir + lenacapavir group were COVID (10%), upper respiratory tract infection (8%) and diarrhea (4%). Drug-related TEAEs leading to discontinuation were reported in 2% of participants in the higher dose lenacapavir group, 2% in the lower dose lenacapavir group and none in the stable baseline regimen group.

These latest findings support the continued evaluation of the combination of bictegravir and lenacapavir for use in people with HIV who are virologically suppressed on complex ART regimens. This investigational combination of bictegravir 75 mg + lenacapavir 50 mg is 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 bictegravir 75 mg + lenacapavir 50 mg versus Biktarvy in virologically suppressed people with HIV.

New Data Support Ongoing Clinical Development of an Investigational, First-in-Class, Once-Weekly Oral Combination HIV Treatment Regimen

GS-4182 is a novel, oral prodrug of lenacapavir that is under development for the treatment of HIV. Results from a nonclinical pharmacology study showed GS-4182 was generally well tolerated with a favorable safety profile. Additionally, a first-in-human Phase 1a study assessed the safety and pharmacokinetics (PK) of GS-4182 in participants without HIV. This randomized, blinded, placebo-controlled study included single ascending doses and multiple ascending doses, and demonstrated that GS-4182 reached mean LEN concentrations rapidly, achieving target efficacy levels. No Grade ≥3 TEAEs, serious TEAEs or discontinuations due to TEAEs occurred. Nine Grade ≥3 treatment-emergent laboratory abnormalities were reported. Both datasets support the future development of GS-4182 as a component of a once-weekly oral combination HIV treatment regimen.

GS-1720 is a selective integrase strand transfer inhibitor (INSTI) being evaluated as a novel, investigational once-weekly antiretroviral agent in combination with long-acting agents with the goal of providing people with HIV with new long-acting options. Previously presented data demonstrated the first proof of concept that GS-1720 has a pharmacokinetic profile suitable for evaluation as a weekly dosing interval. In new nonclinical data presented at AIDS 2024, the safety pharmacology and toxicology profiles of GS-1720 were evaluated in vitro and in animals following oral administration of the agent. Results showed significantly improved antiviral potency compared to bictegravir in vitro and a similar nonclinical virology, pharmacology, and safety profile. Additionally, in a first-in-human study, the safety and PK of single-ascending doses of GS-1720 were evaluated in participants without HIV. Results showed that GS-1720 was generally well tolerated across the doses tested and exhibited a half-life that may be supportive of once-weekly oral dosing.

These data support the ongoing clinical development of GS-1720 and GS-4182 as the components of an investigational, first-in-class, once-weekly oral capsid-inhibitor/INSTI combination regimen for HIV treatment.

Long-Acting, Twice-Yearly Regimen of Lenacapavir and Broadly Neutralizing Antibodies (bNAbs)

Results of a resistance analysis from a previously presented study evaluating the investigational combination of lenacapavir with bNAbs [teropavimab (GS-5423, TAB) + zinlirvimab (GS-2872, ZAB)] showed that high rates of virologic suppression were maintained for six months with twice-yearly dosing during treatment with lenacapavir and bNAbs, including among participants highly susceptible to only one bNAb (n=30), according to the study screening criteria. Three participants experienced virologic rebound, with emergent lenacapavir resistance detected for one participant, who had no resistance to bNAbs and resuppressed with resumption of oral ART. 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 future long-acting combination HIV treatment options.

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.

Lenacapavir is being studied in multiple ongoing early and late-stage development programs and has the potential to offer a diverse set of person-centric options for treatment that could uniquely fit into the lives of people with HIV.

Please see below for the U.S. Indication and Important Safety Information for Sunlenca. 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.

U.S. Indication for Sunlenca

Sunlenca, a human immunodeficiency virus type 1 (HIV-1) capsid inhibitor, in combination with other antiretroviral(s), is indicated for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations.

U.S. Important Safety Information for Sunlenca

Contraindications

• Coadministration: Concomitant administration of Sunlenca is contraindicated with strong CYP3A inducers.

Warnings and precautions

• Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported in patients treated with combination antiretroviral (ARV) therapy.
• Long-acting properties and potential associated risks with Sunlenca: Residual concentrations of Sunlenca may remain in the systemic circulation of patients for up to 12 months or longer. Sunlenca may increase exposure, and potential risk of adverse reactions, to drugs primarily metabolized by CYP3A initiated within 9 months after last injection. Counsel patients regarding the dosing schedule because nonadherence could lead to loss of virologic response and development of resistance. If virologic failure occurs, switch to an alternative regimen if possible. If discontinuing Sunlenca, begin alternate suppressive ARV regimen within 28 weeks from last injection.
• Injection site reactions may occur, and nodules and indurations may be persistent.

Adverse reactions

• Most common adverse reactions (incidence ≥3%, all grades) are injection site reactions (65%) and nausea (4%).

Drug interactions

• Prescribing information: Consult the full prescribing information for Sunlenca for more information on Contraindications, Warnings, and potentially significant drug interactions, including clinical comments.
• Enzymes/transporters: Drugs that are strong or moderate inducers of CYP3A may significantly decrease the concentration of Sunlenca. Drugs that strongly inhibit CYP3A, P-gp, and UGT1A1 together may significantly increase the concentration of Sunlenca. Sunlenca may increase the exposure of drugs primarily metabolized by CYP3A, when initiated within 9 months after the last injection of Sunlenca, which may increase the potential risk of adverse reactions.

Dosage and administration

• Dosage: Initiation with 1 of 2 options, followed by maintenance dosing once every 6 months. Tablets may be taken with or without food.
  • Initiation Option 1: Day 1: 927 mg by subcutaneous injection and 600 mg orally (2 x 300-mg tablets). Day 2: 600 mg orally (2 x 300-mg tablets).
  • Initiation Option 2: Day 1: 600 mg orally (2 x 300-mg tablets). Day 2: 600 mg orally (2 x 300-mg tablets). Day 8: 300 mg orally (1 x 300-mg tablet). Day 15: 927 mg by subcutaneous injection.
  • Maintenance: 927 mg by subcutaneous injection every 26 weeks +/- 2 weeks from date of last injection.
• Missed Dose: During the maintenance period, if more than 28 weeks have elapsed since the last injection and if clinically appropriate to continue Sunlenca treatment, restart the initiation dosage regimen from Day 1, Option 1 or Option 2.

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.

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 or studies within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing and additional clinical trials or studies, including those involving Biktarvy, lenacapavir, teropavimab, zinlirvimab, GS-1720 and GS-4182; uncertainties relating to regulatory applications and related filing and approval timelines, including potential applications for indications currently under evaluation; the possibility that Gilead may make a strategic decision to discontinue development of these programs and, as a result, these programs may never be successfully commercialized for the indications currently under evaluation; 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 March 31, 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 Sunlenca is available at www.gilead.com. U.S. full Prescribing Information for Biktarvy, including BOXED WARNING, is available at www.gilead.com.

Sunlenca, Biktarvy, Gilead and the Gilead logo are 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 (@Gilead Sciences) and LinkedIn, or contact Gilead Public Affairs at public_affairs@gilead.com, 1-800-GILEAD-5 or 1-650-574-3000.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240725176931/en/

Jacquie Ross, Investors investor_relations@gilead.com

Meaghan Smith, Media public_affairs@gilead.com