– Week 24 Results Support Continued Development as a Potential Long-Acting Oral Combination Treatment Option in Virologically Suppressed People with HIV –

– Novel Investigational Combination Regimen has the Potential to be the First Oral Weekly HIV Treatment, Helping to Address Unmet Needs –

FOSTER CITY, Calif., & RAHWAY, N.J.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from the Phase 2 clinical study evaluating the investigational combination of islatravir, an investigational nucleoside reverse transcriptase translocation inhibitor, and lenacapavir, a first-in-class capsid inhibitor. These late-breaking data were presented during an oral session at the 31st Conference on Retroviruses and Opportunistic Infections (CROI). Prior to the late-breaker oral presentation, the key findings were featured in a CROI press conference.

At 24 weeks, the novel investigational combination maintained a high rate (94.2%) of viral suppression (HIV-1 RNA 50 copies/mL at Week 24; the participant later suppressed on islatravir and lenacapavir at Week 30.

The potent antiviral activities, along with pharmacokinetic profiles of islatravir and lenacapavir, support their development as an investigational once-weekly oral combination regimen. Single-tablet daily oral therapies have helped to transform HIV care, but options that allow for less frequent dosing have the potential to address adherence, stigma and other challenges faced by some individuals taking daily oral antiretroviral therapy.

“HIV treatment is not one size fits all – developing once-weekly treatment options could help meet the needs of each individual, aiming toward maximizing long-term outcomes for people with HIV,” said Jared Baeten, Vice President, MD, PhD, HIV Clinical Development, Gilead Sciences. “These promising data presented at CROI help bring us one step closer to our goal of providing a wide range of options that may help transform the HIV treatment landscape.”

In this open-label, active-controlled study (NCT05052996), virologically suppressed adults (n=104) on Biktarvy® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) were randomly allocated in a 1:1 ratio to receive either oral islatravir 2 mg and lenacapavir 300 mg once a week (n=52) or to continue daily oral Biktarvy (n=52). The median age of participants was 40 years. Eighteen percent of participants were assigned female at birth, 50% were non-white, and 29% were Hispanic or Latinx.

Results of the primary endpoint, measured as HIV-1 RNA ≥50 copies/mL (c/mL) at Week 24 per FDA Snapshot algorithm, showed that one participant (1.9%) treated with islatravir and lenacapavir had a viral load of more than 50 copies/mL at Week 24; the participant later suppressed on islatravir and lenacapavir at Week 30. No participants in the Biktarvy group had a viral load of more than 50 copies/mL at Week 24. Results of the secondary endpoint, as measured by the proportion of individuals with HIV-1 RNA <50 c ml at week 24, showed that participants who switched to treatment with once-weekly islatravir and lenacapavir or continued biktarvy both maintained comparable high rates of hiv suppression 24 (94.2% v. 94.2%). < p>

Grade 1 and 2 treatment-related-adverse events (TRAEs) reported in the islatravir and lenacapavir group included dry mouth and nausea (each 3.8%). No grade 1 and 2 TRAEs were reported in the Biktarvy group. No grade 3 or 4 TRAEs related to study drug in either treatment group were reported. Two participants discontinued islatravir and lenacapavir due to adverse events unrelated to the drug. In addition, no differences were seen between treatment groups for changes in CD4+ T cell counts or absolute lymphocyte counts.

“Our strategies for managing and treating HIV must evolve with the needs of the HIV community and we are excited to have these promising first data from the Phase 2 study for islatravir and lenacapavir presented at CROI,” said Dr. Elizabeth Rhee, vice president, global clinical development, Merck Research Laboratories. “Gilead and Merck remain committed to this collaboration and to the development of a potential once-weekly oral therapy for people living with HIV who may need additional options to help maintain viral suppression.”

The Phase 2 study will continue in an open-label fashion through Week 48. Longer-term data will be presented at a future scientific conference.

Islatravir, alone or in combination with lenacapavir, is investigational and not approved anywhere globally. The safety and efficacy of the combination of islatravir and lenacapavir have not been established.

Lenacapavir, marketed as Sunlenca®, is approved in Australia, Canada, the European Union, Israel, Japan, Switzerland, the United Arab Emirates, the United Kingdom and the United States for the treatment of people with multi-drug resistant HIV in combination with other antiretroviral(s).

Please see below for the U.S. Indication and Important Safety Information for Sunlenca. Please also see below for U.S. Indication and Important Safety Information, including Boxed Warning, for Biktarvy.

There is currently no cure for HIV or AIDS.

About islatravir (MK-8591)

Islatravir (MK-8591) is Merck’s investigational nucleoside reverse transcriptase translocation inhibitor under evaluation for the treatment of HIV-1 in combination with other antiretrovirals. For an overview of Merck’s HIV treatment and prevention clinical development program, please click here.

About Sunlenca®

Sunlenca (300 mg tablet and 463.5 mg/1.5 mL injection) [(lenacapavir)] is a first-in-class, long-acting HIV capsid inhibitor indicated for the treatment of HIV infection, in combination with other antiretroviral(s), in adults with multi-drug resistant HIV who are heavily treatment-experienced. Sunlenca is the only HIV treatment option administered twice-yearly. Sunlenca tablets are approved for oral loading during initiation of Sunlenca treatment, prior to or at the time of the first long-acting lenacapavir injection depending on initiation option.

The multi-stage mechanism of action of Sunlenca’s active pharmaceutical agent, lenacapavir, is distinguishable from other currently approved classes of antiviral agents. While most antivirals act on just one stage of viral replication, Sunlenca 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 developed as a foundation for future HIV therapies developed by Gilead. The goal is to offer both long-acting oral and injectable options with various dosing frequencies in combination with other antiretroviral agents for treatment or as a single agent for prevention. This approach aims to help address the individual needs and preferences of people with HIV and people who could benefit from pre-exposure prophylaxis (PrEP). The use of lenacapavir for HIV prevention is investigational and the safety and efficacy of lenacapavir for this use has not been established. Lenacapavir is being evaluated as a potential long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead’s HIV prevention and treatment research program.

About Merck

At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.

Merck’s Commitment to HIV

For more than 35 years, Merck has been committed to scientific research and discovery in HIV. Today, we are developing a series of antiviral options designed to help people manage HIV and protect people from HIV, with the goal of reducing the growing burden of infection worldwide. We remain committed to collaborating with others in the global HIV community to address the complex challenges that impede progress toward ending the epidemic.

About Gilead Sciences in HIV

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 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 was recognized as the number one philanthropic funder of HIV-related programs in a report released by Funders Concerned About AIDS.

Learn more about Gilead’s unique collaborations worldwide and the work to help end the global HIV epidemic.

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: There is insufficient human data on the use of SUNLENCA during pregnancy. An Antiretroviral Pregnancy Registry (APR) has been established.
• Lactation: Individuals infected with HIV-1 should be instructed not to breastfeed, due to the potential for HIV-1 transmission.

U.S. Indication for Biktarvy

Biktarvy is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and pediatric patients weighing at least 14 kg who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and 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)