Merck steps up as ‘meaningful competitor’ to Gilead with HIV pill approval

FDA Approves Merck's Idvynso for Virologically Suppressed HIV-1

Merck's daily pill Idvynso (doravirine and islatravir) received FDA approval on April 22, 2026, for the treatment of virologically suppressed HIV-1 in adults. The drug, intended to replace current antiretroviral regimens, is set to launch in the U.S. after May 11. This approval positions Merck as a more significant competitor in the HIV market, aiming to establish Idvynso as a new anchor treatment, despite Gilead's longstanding dominance with products like Biktarvy. The decision is supported by clinical data demonstrating non-inferior maintenance of viral suppression compared to Biktarvy. This move also strategically diversifies Merck's revenue ahead of its blockbuster cancer drug Keytruda's patent expiration.

• The FDA has approved Merck’s Idvynso, a once-daily pill combining doravirine and islatravir, for adults with virologically suppressed HIV-1. Slated for U.S. market entry after May 11, Idvynso is designed as a complete regimen to replace existing antiretroviral therapies, specifically for patients without a history of treatment failure or known resistance to doravirine. This approval marks Merck's strategic push to become a more substantial player in the HIV treatment landscape.
• The approval of Idvynso is underpinned by data from two randomized, active-controlled studies. These trials demonstrated that switching to Idvynso resulted in non-inferior maintenance of viral suppression when compared to continuing Biktarvy treatment. Merck emphasizes that Idvynso expands therapeutic options, offering a new oral treatment choice beyond currently available regimens, thereby enhancing diversity in HIV-1 care.
• Idvynso's approval is a critical component of Merck's long-term strategy to diversify its revenue streams. With its top-selling cancer drug, Keytruda, facing key patent protections expiring in 2028, and a more significant erosion expected around 2033, Idvynso provides a new growth driver. This helps mitigate the financial impact of Keytruda's eventual loss of exclusivity, strengthening Merck's overall portfolio.

Idvynso's Pivotal Trial Design and Efficacy for Virologically Suppressed HIV-1

The key trials for virologically suppressed HIV-1 in adults demonstrate consistent study designs focused on switch strategies and maintenance of viral suppression. These pivotal studies primarily employed randomized, controlled designs with noninferiority endpoints and standardized viral load assessment methodologies.

Navigating the Evolving HIV-1 Treatment Landscape: Idvynso's Position

The HIV-1 treatment landscape for virologically suppressed adults has undergone significant evolution over the past five years, with the most notable advancement being the shift from three-drug regimens (3DR) to two-drug regimens (2DR). Multiple large randomized trials have demonstrated the virological non-inferiority of certain two-drug combinations versus three-drug comparators, with improved tolerability profiles and reduced risk of drug interactions and toxicity. The emergence of doravirine and islatravir represents the first non-INSTI-based two-drug regimen, achieving non-inferiority at week 48 with viral loads ≥50 copies/mL in only 1.4% of participants compared to 4.9% on baseline antiretroviral therapy. Dolutegravir-based dual therapies, including dolutegravir/lamivudine combinations, have shown comparable efficacy to triple therapy regimens while offering simplified dosing and potentially fewer adverse effects.

The most transformative development has been the introduction of long-acting injectable therapies, with cabotegravir plus rilpivirine representing the first complete long-acting injectable regimen approved for maintenance therapy. Phase III trials including FLAIR, ATLAS, and ATLAS-2M demonstrated non-inferiority of this combination versus oral therapy, with real-world studies confirming these findings. The JABS study showed 97.2% of injections administered within correct dosing windows with no virological failures, while the BEYOND study reported 97% of participants maintaining viral load <50 copies/mL at month 12. These long-acting therapies address critical adherence challenges, with 97% of participants preferring injectable treatment over oral therapy and significant reductions in treatment-related stigma and disclosure anxiety.

Switching strategies have also evolved considerably, with recent data demonstrating high efficacy when transitioning from NNRTI-based regimens to integrase inhibitor-based combinations. Switching to bictegravir/emtricitabine/tenofovir alafenamide from rilpivirine-based regimens achieved 95.7% viral suppression at 12 months with virological failure rates of only 0.93% and no resistance mutations detected. Treatment discontinuations remained rare at 2.8%, and beneficial metabolic effects including decreased LDL cholesterol were observed. These developments collectively represent a paradigm shift toward simplified, more tolerable treatment options that maintain robust virological efficacy while addressing patient-centered outcomes including quality of life, treatment satisfaction, and adherence challenges.

Addressing Unmet Needs and Diversifying HIV-1 Treatment Options

Despite significant advances in HIV-1 treatment, current therapeutic approaches for virologically suppressed patients face substantial challenges that limit optimal care delivery. These limitations encompass drug-related toxicities, resistance development, adherence barriers, and emerging complications from polypharmacy as patients age with HIV.

• Drug resistance and treatment failure: Drug resistance remains a major factor contributing to antiretroviral therapy failure, with many patients unable to achieve or maintain viral suppression due to existing or developing resistance, poor adherence, and pharmacokinetic problems

• Significant toxicity burden: High rates of adverse events occur with current HAART regimens, with 95% of patients experiencing adverse events during 52-week treatment periods and 18.7% withdrawing due to treatment-related toxicities including hepatotoxicity, gastrointestinal disorders, bone marrow suppression, and rash

• Adherence and pill burden challenges: High pill burdens and serious side effects create substantial adherence problems, while the need for lifelong therapy raises concerns about long-term toxicity, cost, and patient tolerance

• Limited treatment options for resistant virus: Broadly-neutralizing monoclonal antibodies show substantial baseline resistance and rapid resistance development when used as monotherapy, while heavily treatment-experienced patients with multidrug-resistant HIV-1 have few remaining therapeutic options

• Drug interaction and polypharmacy concerns: Rising prevalence of non-communicable diseases among people living with HIV creates additional challenges through increased polypharmacy and potential drug interactions with antiretroviral regimens

• Geographic disparities in access to newer therapies: Long-acting injectable formulations and simplified regimens like dolutegravir/lamivudine, while available in high-resource settings, remain largely inaccessible in sub-Saharan Africa where they are restricted to clinical trials

• Management of long-acting formulation discontinuation: Strategies to manage toxicity and falling drug concentrations after missed doses or treatment discontinuation are critical considerations for newer long-acting antiretroviral approaches to prevent resistance development

Merck's Two-Drug HIV Regimen: A New Anchor

The recent FDA approval of Idvynso, Merck's fixed-dose combination of doravirine and islatravir, marks a pivotal moment for both the company and the HIV treatment paradigm. For Merck, this represents a strategic entry into the highly competitive HIV market, aiming to challenge the dominance of established players with a novel, once-daily oral therapy. The drug's approval for virologically suppressed adults, supported by data demonstrating non-inferiority to leading three-drug regimens like bictegravir/emtricitabine/tenofovir alafenamide, positions it as a compelling alternative.

Idvynso's appeal lies in its two-drug composition, offering a potential reduction in pill burden and a distinct mechanism of action without an integrase strand transfer inhibitor. Doravirine, an NNRTI, is known for its favorable safety profile, including reduced central nervous system adverse events and a lower propensity for drug-drug interactions compared to older NNRTIs. Islatravir, a nucleoside reverse transcriptase translocation inhibitor, brings potent antiviral activity and a high barrier to resistance. This combination could be particularly attractive for patients seeking to switch from more complex regimens or those experiencing side effects from current therapies.

However, the journey for islatravir has not been without its complexities. Earlier clinical investigations of a higher islatravir dose (0.75 mg) in combination with doravirine revealed decreases in CD4 cell and total lymphocyte counts, leading to the discontinuation of that specific dose for further development. This underscores the importance of the carefully selected 0.25 mg islatravir dose in the approved Idvynso formulation, which has demonstrated a more favorable safety profile in recent trials. While the combination generally exhibits minimal drug-drug interaction potential, clinicians must remain mindful of contraindications with strong CYP3A inducers, a known limitation for doravirine. As Idvynso enters the market, its real-world uptake will depend on its ability to consistently deliver on its promise of efficacy, safety, and convenience, offering a valuable new option for long-term HIV management.