Lenacapavir Sodium

– Novel Investigational Combination Regimen is Advancing to Phase 3 and has the Potential to Become the First Weekly Oral HIV Treatment – FOSTER CITY, CA, & RAHWAY, NJ, USA I October 19, 2024 I Gilead Sciences, Inc. (Nasdaq: GILD) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced new results from a Phase 2 clinical study evaluating the investigational combination of islatravir, an investigational nucleoside reverse transcriptase translocation inhibitor, and lenacapavir, a first-in-class HIV-1 capsid inhibitor. These late-breaking data were presented during an oral session at ID Week 2024 , taking place in Los Angeles, and virtually, from October 16-19. At 48 weeks, the novel investigational combination maintained a high rate (n=49; 94.2%) of viral suppression (HIV-1 RNA <50 copies/mL) in virologically suppressed adults, a secondary endpoint of the study. Zero participants had a viral load of ≥50 copies/mL at Week 48. Week 24 results, including the study’s primary endpoint, were previously presented at the 31st Conference on Retroviruses and Opportunistic Infections (CROI). “The future of HIV treatment is person-centered, with long-acting options tailored to help meet the needs and preferences of people affected by HIV,” said Jared Baeten, MD, PhD, Senior Vice President, Virology Therapeutic Area Head, Gilead Sciences. “There is no ‘one size fits all’ approach. The complexities of HIV care require putting people first in the development of biomedical innovations as we keep striving to offer options for all those living with HIV. These data presented at IDWeek demonstrate our commitment to continuous scientific discovery aimed at further transforming 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 (20-76). Eighteen percent of participants were assigned female at birth, 50% were non-white, and 29% were Latine. The proportion of individuals with HIV-1 RNA <50 c/mL at Week 48 by FDA snapshot algorithm (a secondary endpoint), showed that participants who switched to treatment with once-weekly islatravir and lenacapavir (ISL + LEN) or continued Biktarvy maintained comparable high rates of HIV suppression at Week 48 (94.2% v. 92.3%, respectively). No participants treated with either ISL + LEN or Biktarvy had a viral load of ≥ 50 copies/mL at Week 48 (another secondary endpoint). Treatment-related-adverse events (TRAEs), as attributed by study investigator, were experienced by 19.2% of participants (n=10/52) in the ISL + LEN group and the most common were dry mouth (n=2/52; 3.8%) and nausea (n=2/52; 3.8%). TRAEs were reported by 5.8% of participants in the Biktarvy group (n=3/52). No grade 3 or 4 TRAEs related to the study drug were reported in either treatment group. Two participants (n=2/52; 3.8%) discontinued ISL + LEN due to adverse events unrelated to the drug. At Week 48 no significant differences were seen between treatment groups in mean change from baseline in CD4+ T-cell counts or absolute lymphocyte counts. No participants discontinued due to a decrease in CD4+ T-cell or lymphocyte counts. “Daily single-tablet regimens have helped to transform HIV care but can be challenging for some people to maintain. Novel HIV treatment options that allow for less frequent oral dosing have the potential to help support adherence, and address stigma faced by some individuals taking daily oral therapy,” said Dr. Elizabeth Rhee, Vice President, Global Clinical Development, Merck Research Laboratories. “We are pleased to see these encouraging 48-week data for this once-weekly oral combination regimen and advance to phase 3 clinical trials in collaboration with Gilead.” Along with these most recent study results, the potent antiviral activities, and pharmacokinetic profiles of islatravir and lenacapavir support their continued development as an investigational once-weekly oral combination regimen for use in people with HIV who are virologically suppressed. This investigational combination of weekly oral ISL 2 mg + LEN 300 mg is being further evaluated as a fixed-dose combination regimen in two Phase 3 studies ( NCT06630286 and NCT06630299 ) in virologically suppressed people with HIV. Islatravir 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 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. The use of lenacapavir for HIV treatment in virologically suppressed individuals is investigational and not approved anywhere globally. Please see below for the 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) and Merck’s HIV Research Islatravir (MK-8591) is Merck’s investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI) under evaluation in multiple ongoing early and late-stage clinical studies in combination with other antiretrovirals for the treatment of HIV-1. Studies with islatravir are designed to offer different dosing options as potential daily and once-weekly treatments. For an overview of Merck’s HIV treatment and prevention clinical development program, please click here . About Lenacapavir 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. 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. 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. 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 leading to scientific breakthroughs that have helped change HIV treatment. Our work has been pioneering in the development of new options across multiple drug classes to help those impacted by 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 want to ensure people are not defined by HIV and our work focuses on transformational innovations, collaborations with others in the global HIV community, and access initiatives aimed at the goal of helping to end the HIV epidemic for everyone. 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, COVID-19, cancer, and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif. About Gilead Sciences in HIV For 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. U.S. full Prescribing Information for Biktarvy, including BOXED WARNING , is available at www.gilead.com . SOURCE: Gilead Sciences

Gilead and Merck said their once-weekly pill to treat HIV resulted in a comparable level of viral suppression compared to a daily regimen in a 48-week study. In a rare partnership between large pharmas, the companies are now starting two Phase 3 studies for the weekly pill, which is a combination of Merck’s islatravir and Gilead’s lenacapavir, which is marketed as Sunlenca for certain patients with HIV. The currently available pills have to be taken every day, but Gilead and Merck hope their experimental drug can provide a long-acting oral option for people with HIV. There is one complete long-acting option on the US market in ViiV’s Cabenuva, which is a once-monthly or every-other-month shot. “The treatment options that exist — for some people — are not completely workable in people’s lives,” Jared Baeten, Gilead’s virology therapeutic area head, said in an interview with Endpoints News before the data were released. “And that is, in spite of, for the rest of individuals, the once-a-day therapy is particularly well-tolerated.” In the Phase 2 open-label study, 104 adults on Gilead’s Biktarvy were randomized to receive either Merck and Gilead’s experimental treatment regimen or continue Biktarvy, which is a daily pill combining three HIV medications. At 48 weeks, those who received the experimental combo saw 94.2% HIV suppression, while those who continued on Biktarvy saw 92.3% HIV suppression. No participants at week 48 had a viral load of 50 copies/mL or more, which is often used as a threshold for viral load on HIV tests. The drugs provide two different mechanisms to stop the virus from making more copies of itself. Lenacapavir tackles the virus’ protective shell, while islatravir inhibits the reverse transcriptase, which is needed for the virus to replicate. The data build on primary 24-week results that were presented earlier this year and set up the companies to move the combo into pivotal trials. One of the Phase 3 studies, like the Phase 2 trial, will be open-label, while the other will be blinded. “We’ve talked to patients, providers and prescribers, government — people tell us that some people would want a longer-acting pill, so a pill you take less often,” Baeten said, “and some people would want an injection. And actually, when we really break down our market research, it’s about 50/50.” A key data point from the Phase 2 study showed that there were no differences in immune cell count changes between the Biktarvy and experimental groups. In 2021, Merck paused development of islatravir after it led to a drop in counts of lymphocytes and CD4+ T cells in a different mid-stage study. Then, in 2022, the pharma company restarted development using a lower dose of islatravir in its combination studies, including this Phase 2 trial, though it stopped work on a once-monthly oral version for HIV prevention. Lenacapavir is approved as Sunlenca for use in combination with other antiretroviral drugs to treat people with multi-drug resistant HIV infection. Gilead is also planning to seek approval for a six-month injection of lenacapavir for HIV prevention after presenting compelling results from two Phase 3 studies. They plan to begin regulatory filings at the end of this year.