Merck Spotlights Weekly HIV Treatment, Monthly PrEP as $5B Growth Opportunity

Key Points

• Merck reported positive Phase III results for its once-weekly oral islatravir/lenacapavir HIV regimen, showing non-inferior viral suppression versus daily therapies, no treatment-emergent resistance, and lower reported treatment burden. The company plans global regulatory submissions, with Gilead leading U.S. commercialization.
• Merck is advancing additional long-acting options, including its wholly owned weekly islatravir/ulonivirine treatment toward Phase III and once-monthly oral alimatravir PrEP, with pivotal PrEP trial results expected in 2027. The monthly PrEP candidate is designed to offer rapid protection, discreet use, and a one-week missed-dose window.
• Merck estimates its HIV portfolio could represent more than $5 billion in non-risk-adjusted opportunity by the mid-2030s, supported by growth in the treatment and PrEP markets and increasing adoption of long-acting regimens.

Merck & Co., Inc. NYSE: MRK outlined its HIV treatment and prevention strategy at an investor event following the International AIDS Conference, highlighting Phase III results for a once-weekly oral HIV regimen and its plans for a monthly oral pre-exposure prophylaxis, or PrEP, candidate.

Company executives said Merck’s pipeline is focused on reducing treatment burden for people living with HIV and expanding prevention options for people at risk of infection. The company cited the continuing need for alternatives to daily pills and injectable regimens, particularly as patients age and manage comorbidities and multiple medications.

Weekly Treatment Data

Dr. Liz Rhee, Merck’s vice president of clinical research for infectious diseases, presented results from the Phase III ISLEND-1 and ISLEND-2 trials of once-weekly oral islatravir plus lenacapavir, a regimen being developed with Gilead Sciences.

ISLEND-1 was a double-blinded global study involving 607 virologically suppressed adults. The weekly two-drug regimen was compared with daily bictegravir/emtricitabine/tenofovir alafenamide, or B/F/TAF. Rhee said islatravir plus lenacapavir achieved non-inferior efficacy at 48 weeks, with viral suppression rates above 90% and no treatment-emergent resistance to either drug.

In the open-label ISLEND-2 study, 626 participants were randomized to receive the weekly regimen or a range of daily standard-of-care therapies. The weekly regimen also demonstrated non-inferior efficacy, while viral suppression remained approximately 95%, according to Rhee. Participants reported greater satisfaction and less treatment burden with the weekly regimen than with their prior daily therapies.

Across both studies, Rhee said the regimen was generally well tolerated, with safety comparable to the control regimens. Merck reported no clinically meaningful changes in lymphocyte counts, CD4 counts, or body weight, and said no participants discontinued treatment because of declining CD4 or absolute lymphocyte counts.

Chief Medical Officer Eliav Barr addressed a question regarding a small statistical difference in CD4-count changes in ISLEND-2. Barr said Merck did not consider the finding clinically meaningful, citing a baseline imbalance and the absence of a similar pattern in ISLEND-1 or the company’s Phase II islatravir/ulonivirine study. He said the company viewed the result as likely reflecting regression to the mean.

Merck said it plans to submit islatravir plus lenacapavir to global regulatory authorities. Under the collaboration, Gilead will lead U.S. commercialization of the long-acting oral program, while Merck will lead commercialization outside the United States. The companies will share global development and commercialization costs on a 60/40 basis, respectively, and will split global product revenue equally up to approximately $2 billion, after which Gilead will receive 65% and Merck 35%.

Second Weekly Program Moving Toward Phase III

Merck also discussed islatravir plus ulonivirine, its wholly owned investigational weekly oral regimen. The company reported that a Phase IIb trial showed the regimen maintained viral suppression through week 24, with no participants in the treatment group recording HIV RNA of 50 copies per milliliter or greater. More than 94% of participants remained virally suppressed, and Merck reported no treatment-emergent resistance cases.

Rhee said the regimen was generally well tolerated and had an adverse-event profile comparable to daily B/F/TAF. Merck plans to advance the program into the SYMPHORIA Phase III program, including trials in virologically suppressed adults switching from daily treatment and in treatment-naive adults. SYMPHORIA 1 and 2 are expected to begin in the first half of 2027, while results from the Phase II component of SYMPHORIA 3 are anticipated in the first half of 2027.

The company said both weekly regimens were designed with approximately a seven-day “forgiveness” window for missed doses.

Monthly Oral PrEP Program

Merck also highlighted alimatravir, its investigational once-monthly oral PrEP candidate. The company said the 11-milligram dose is expected to provide protective drug levels within one hour, without a loading dose. Merck said Phase III EXPrESSIVE 10 and 11 trials are expected to report results in 2027.

Executives positioned the monthly oral approach as a potentially discreet alternative that does not require healthcare-provider administration. Rhee said the dose also provides approximately one week of forgiveness if a monthly dose is missed.

Merck recently announced plans, contingent on approval, to support access to alimatravir in low- and middle-income countries through voluntary licensing agreements covering more than 129 countries, regional manufacturing support, and investments intended to facilitate access following approval.

Commercial Outlook

Brian Foard, executive vice president and president of Merck’s Specialty, Pharma and Infectious Diseases Business Unit, said the company sees a non-risk-adjusted HIV opportunity exceeding $5 billion by the mid-2030s across its marketed and investigational portfolio. That portfolio includes IDVYNSO, Merck’s newly approved daily oral treatment, the two weekly treatment programs, and alimatravir.

Foard said Merck estimates the HIV treatment market was about $26 billion in 2025 and could grow to roughly $32 billion by the mid-2030s. He said the PrEP market, estimated at about $4 billion currently, could more than double over time. Gregg Szabo, head of Merck’s global HIV franchise, said the company expects long-acting regimens to represent a substantial share of the treatment market over time and sees weekly oral options potentially reaching about one-third of the overall treatment market.

About Merck & Co., Inc. (NYSE:MRK)

Merck & Co, Inc is a global biopharmaceutical company engaged in the discovery, development, manufacture and marketing of prescription medicines, vaccines, biologic therapies and animal health products. Its portfolio spans multiple therapeutic areas with a particular emphasis on oncology, vaccines and infectious disease, as well as therapies for metabolic and chronic conditions. Among its well-known products are the cancer immunotherapy Keytruda (pembrolizumab) and the human papillomavirus vaccine Gardasil; the company also markets a range of medicines and vaccines for veterinary use through Merck Animal Health.

Founded in the late 19th century as the U.S.

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