FDA approves Merck’s IDVYNSO (doravirine/islatravir)

Approval and indication

The FDA approved IDVYNSO, a once-daily single-tablet regimen (100 mg doravirine/0.25 mg islatravir) to replace current antiretroviral therapy in adults virologically suppressed (HIV-1 RNA <50 copies/mL) with no prior virologic failure and no doravirine resistance substitutions; available in pharmacies after May 11.

Mechanism

Doravirine is an NNRTI; islatravir is a next-generation NRTI that inhibits reverse transcriptase translocation causing immediate chain termination and induces delayed chain termination.

Phase 3 trials and efficacy

Two randomized non-inferiority trials (Trials 052 and 051) evaluated switch to IDVYNSO; 708 participants received IDVYNSO overall. Trial 052 (n=513 randomized; 342 vs 171 from BIC/FTC/TAF) showed 1% with HIV-1 RNA ≥50 copies/mL in both arms and Week-48 suppression 92% vs 94%; Trial 051 (n=551 randomized; 366 vs 185) showed 1% vs 5% (treatment difference -3.6%, 95% CI -7.8 to -0.8) and Week-48 suppression 96% vs 92%.

Safety and tolerability

Safety was generally comparable to three-drug regimens; discontinuations due to adverse events were 3% vs 2% (Trial 052) and 0.5% vs 2% (Trial 051). Reported adverse reactions ≥2% included diarrhea, dizziness, fatigue, abdominal distention, headache and weight increase; severe skin reactions (SJS/TEN) and DRESS were reported and one case of severe immune thrombocytopenia occurred.

Drug interactions and special populations

IDVYNSO is a complete regimen and should not be coadministered with strong CYP3A inducers or with lamivudine or emtricitabine; rifabutin requires dose timing adjustment, and coadministration with dCK substrates or ADA inhibitors is not recommended; 81 participants were ≥65 years with no overall differences identified but increased sensitivity in some older individuals cannot be ruled out; IDVYNSO has no activity against HBV and HBV coinfected patients should be monitored.