Doravirine/Islatravir

The US FDA approved Idvynso (doravirine/islatravir) for Merck, marking the first non-integrase strand transfer inhibitor (INSTI), tenofovir-free, once-daily complete two-drug regimen to reach approval for HIV-1 treatment in adults. The fixed-dose combination of 100 mg doravirine and 0.25 mg islatravir is indicated as a switch regimen for virologically suppressed adults with no history of virologic treatment failure and no known resistance substitutions associated with doravirine. The approval covers use in adults with HIV-1 RNA below 50 copies per mL on a stable antiretroviral regimen for at least three months. Idvynso is a complete regimen; co-administration with other antiretrovirals is not recommended. The drug is contraindicated with strong CYP3A enzyme inducers and with lamivudine or emtricitabine, as co-administration may reduce islatravir-triphosphate concentrations and compromise efficacy. Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported with doravirine-containing regimens, and one case of Drug Rash with Eosinophilia and Systemic Symptoms was observed during clinical trials. The approval is supported by Week 48 data from two randomized, active-controlled, non-inferiority Phase III trials. Trial 052 (NCT05630755) was a double-blind study in 513 virologically suppressed adults previously receiving bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), randomized 2:1 to switch to Idvynso or continue BIC/FTC/TAF. At Week 48, 1% of participants in each arm had HIV-1 RNA ≥50 copies/mL (treatment difference 0.9%, 95% CI: -1.9%, 2.9%), with 92% of Idvynso recipients maintaining viral suppression versus 94% on BIC/FTC/TAF. Trial 051 (NCT05631093) enrolled 551 participants switching from a range of antiretroviral regimens, including 64% on INSTI-based therapy. In this open-label study, 1% of Idvynso recipients versus 5% of those continuing baseline therapy had HIV-1 RNA ≥50 copies/mL at Week 48 (treatment difference -3.6%, 95% CI: -7.8%, -0.8%), with 96% versus 92% maintaining suppression. Safety profiles across both trials were comparable to comparator arms, with adverse events leading to discontinuation in 3% and 0.5% of Idvynso recipients in Trials 052 and 051, respectively. The approval adds a mechanistically distinct oral option to a treatment landscape that has been shaped predominantly by INSTI-based regimens. Gilead’s Biktarvy (BIC/FTC/TAF) and ViiV Healthcare’s Dovato (dolutegravir/lamivudine) have become the reference standards for virologically suppressed adults, while ViiV’s long-acting injectable Cabenuva (cabotegravir/rilpivirine) addresses the growing demand for less frequent dosing. Idvynso enters this field as the only approved oral two-drug regimen that avoids both INSTIs and tenofovir, a profile relevant to patients managing renal impairment, bone density concerns, or INSTI-associated metabolic effects including weight gain. Islatravir’s dual mechanism — translocation inhibition and delayed chain termination — distinguishes it from conventional NRTIs, and its activity at low doses underpins the two-drug strategy. The published Phase III data supporting the approval appeared in The Lancet HIV in 2024, including a head-to-head comparison against BIC/FTC/TAF by Mills et al. and a broader switch study by Molina et al. Islatravir’s broader role in Merck’s HIV pipeline extends beyond the approved daily formulation. The company is evaluating islatravir in combination with Gilead’s lenacapavir as a potential once-weekly oral regimen in the Phase III ISLEND-1 (NCT06630286) and ISLEND-2 (NCT06630299) trials, and in combination with the investigational NNRTI ulonivirine (MK-8507) in Phase IIb development. A separate once-monthly oral PrEP candidate, MK-8527, has entered Phase III evaluation in collaboration with the Gates Foundation, targeting HIV acquisition in women and adolescent girls in sub-Saharan Africa. These programs reflect a broader industry shift toward reducing dosing frequency while preserving or improving the tolerability profile that has defined the modern ART era. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

Idvynso is the first non-INSTI, tenofovir-free, two-drug regimen to get the FDA’s blessing. Credit: Tatyana Frolova / Shutterstock.com. MSD (Merck & Co) has secured a US approval for its two-drug human immunodeficiency virus (HIV) combination therapy, Idvynso (doravirine/islatravir), as the company looks to secure a slice of the lucrative market. Once-daily Idvynso was given the US regulatory greenlight based on the results of the Phase III MK-8591A-051 and MK-8591A-052 (NCT05631093; NCT05630755) trials, which found that patients switched from Gilead’s SoC therapy, Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide), maintained viral suppression at a non-inferior level when taking Idvynso daily. This means that American patients who are virologically suppressed and on a stable antiretroviral (ART) regimen can now be switched to Idvynso, provided they have not previously experienced virologic treatment failure or doravirine resistance. According to Anaelle Tannen, infectious disease analyst at GlobalData, Idvynso’s regulatory greenlight reflects a broader shift in the HIV treatment landscape away from traditional three-drug combinations toward simpler, potentially more tolerated options. Currently, the HIV market is dominated by Gilead’s three-drug regimen, Biktarvy, though GSK’s dual therapy, Dovato (dolutegravir/lamivudine), also holds a strong share. Unlike Biktarvy and Dovato, however, Idvynso does not contain an integrase strand transfer inhibitor (INSTI), which can be linked to tolerability issues. Because of its departure from reliance on INSTIs, Tannen says that Idvynso will likely see virologically suppressed patients switch, particularly those who need alternatives due to “tolerability or class-related issues”. However, Tannen does not foresee Idvynso displacing established first-line SoC therapies like Biktarvy, as they have better physician familiarity and established safety and efficacy in HIV. According to patient-based forecasts from GlobalData, parent company of Pharmaceutical Technology , Biktarvy’s sales will peak at $13.2bn in 2032, while Idvynso will pull in $1.6bn that same year. For Idvynso to differentiate itself in the long term, Tannen notes that the drug must demonstrate “clear advantages in weight neutrality or reduced metabolic impact”, which has been a side effect linked to INSTIs like dolutegravir and bictegravir. Idvynso’s combinatory potential While analysts do not predict that Idvynso will have a SoC-changing market impact as a monotherapy, MSD is taking another shot at glory on the HIV market through a late-stage combination programme, which will see the company gauge the potential of Idvynso plus Gilead’s HIV drug, Sunlenca (lenacapavir), as a once-weekly treatment option. The therapeutic duo has already shown promise in a Phase II trial , where it maintained viral suppression on a weekly dosing regimen for two years. If approved, Idvynso-Sunleca could become the first oral treatment option for HIV with this dosing pattern. A recent report from GlobalData projects the global HIV marketplace to experience modest growth during the forecast period, as the indication becomes increasingly competitive.