FDA approves Merck’s Once-Daily IDVYNSO (doravirine/islatravir)

Merck announced the FDA approval of IDVYNSO (DOR/ISL), one week earlier than the designated FDA PDUFA of April 28^th. The regimen has been approved for the treatment of HIV-1 infection in adults to replace the current ART in those who are virologically suppressed (HIV-1 RNA < 50c/mL) on a stable ART with no history of virologic treatment failure and no known substitutions associated with resistance to doravirine (FDA label, FDA Website). 

it is expected Merck to purse a TN label expansion and use IDVYNSO to establish prescriber experience with ISL which is the anchor to the rest of Merck’s HIV Tx pipeline (ISL/LEN and ISL/ULO).

Key Details:

• IDVYNSO is described as “the first and only non-INSTI, tenofovir-free, once-daily, complete two-drug regimen to demonstrate non-inferior efficacy in a head-to-head Phase 3 trial versus three-drug regimen Biktarvy”.
  • In the press release, Merck reiterated 48-week IDVYNSO data that was presented at CROI 2025 (MK-8591A-051 and MK-8591A-052) highlighting across the 2 trials, a total of 708 participants received IDVYNSO; of these 81 (11%) participants were aged 65 years and older, including 10 (1%) aged 75 years and older
• The press release also states that IDVYNSO will be available in pharmacies after May 11, 2026.
• Merck also updated its product page with the IDVYNSO label and patient product information, which includes considerations for prescribers:
  • Contraindications:  IDVYNSO is contraindicated when co-administered with lamivudine (3TC), emtricitabine (FTC), and strong CYP3A inducers.
  • Drug Interactions:  Co-administration with moderate CYP3A inducers, deoxycytidine kinase (dCK) substrates, or adenosine deaminase (ADA) inhibitors is not recommended.
  • Use in Specific Populations: IDVYNSO does not have activity against hepatitis B virus (HBV).
  • Adverse Reactions:  most common AEs (≥2% all grades) were diarrhea, dizziness, fatigue, abdominal distension, headache, and increased weight.
  • Warnings and Precautions:  severe skin reactions including Stevens-Johnson Syndrome (SJS)/ Toxic Epidermal Necrolysis (TEN) and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)

CI Assessment:

• Despite demonstrating non-inferiority in Ph3 trials compared to B/F/TAF (MK-8591A-052) and SOC ART (MK-8591A-051), IDVYNSO shows a lack of clear clinical differentiation.  Given the available Ph3 data, there is no clear unmet need that this regimen aims to address.
• Merck is leveraging the ‘unique’ 2DR, non-INSTI, TAF-free profile demonstrating non-inferior efficacy vs INSTI-based 3DR Biktarvy of as IDVYNSO’s key differentiators. While Merck has been recycling this messaging in prior PRs and investor presentations, explicit ‘TAF-free’ messaging is now being highlighted.
  • This represents a more direct comparison to B/F/TAF, as previously seen with ViiV’s Dovato messaging.
• As IDVYNSO’s label also indicates CYP3A pathway involvement, its DDI profile remains undifferentiated against other approved daily orals.
  • Additionally, warnings against severe skin reactions (SJS/TEN and DRESS) may hinder messaging on DOR/ISL as an optimal regimen for OPWH “managing other health conditions”.
• While the current approval is for VS PWH, Merck is likely to use the positive DOR/ISL TN data (Ph3 MK-8591A-053) to pursue a label expansion in this population.  A potential TN label update could occur as early as Feb 2027.
• IDVYNSO represents the first approved ISLregimen, ISL anchors the rest of Merck’s HIV pipeline (ISL/LEN and ISL/ULO).  As such, Merck may use the upcoming approval to familiarize HCPs with ISL and as a launchpad for cross-ISL pipeline portfolio messaging.