Merck richiede approvazione FDA per Doravirin/Islatravir (DOR/ISL), primo regime orale a duplice terapia senza inibitori dell’integrasi per il trattamento dell'HIV

Merck announced the FDA acceptance of the New Drug Application (NDA) for DOR/ISL (NNRTI/NRTTI) its investigational, once-daily, oral 2DR for VS PWH, with a PDUFA date of April 28, 2026.  

• The NDA was based on findings from two pivotal Ph3 DOR/ISL trials; MK-8591A-051 and MK-8591A-052, investigating DOR (100mg)/ISL (0.25mg) (oral, QD) switch from either baseline ART, or B/F/TAF respectively in VS PWH.
  • Week 48 data demonstrated that DOR/ISL was non-inferior to BL ART (MK-8591A-051) and B/F/TAF, however, did not meet superiority criteria (MK-8591-052).  
• The headline of the press release noted that if approved, DOR/ISL would be the “first FDA-approved 2DR without an INSTI that demonstrated non-inferior efficacy and a generally comparable safety profile to the 3DR InSTI-based regimen, BIC/FTC/TAF, in a Phase 3 pivotal trail”.

Assessment:

• The press release highlights the pivotal data presented at CROI 2025, where DOR/ISL demonstrated non-inferior efficacy and comparable safety vs baseline ART and B/F/TAF. However, the data showed no significant differentiation in other outcomes (e.g. weight), limiting clinical differentiation.
• In the absence of key differentiators, Merck is leaning on DOR/ISL being a “2DR regimen without an INSTI”, as spotlighted in the press release headline.
  • At IAS 2025, Merck will be presenting a medical symposium on the DOR/ISL resistance profile based on its Ph3 data, along with a poster on switching to DOR/ISL in PWH with archived M184I/V mutations.
  • Merck also seems to be mirroring ViiV’s 2DR messaging, targeting those “managing comorbidities” or “navigating complex medication regimens” (two of the “diverse needs” cited in the PR), which is largely associated with OPWH. With Dovato nearing LoE (US, 2029), Merck may attempt to position DOR/ISL as the gold standard 2DR in this population.
• DOR/ISL is also being assessed in TN PWH, with the Ph3 trial (NCT05705349) reaching PCD in October 2025. If successful, this could enable a subsequent label expansion and positioning of DOR/ISL as an option for ART-naïve individuals.