Merck (MSD) today announced that the U.S. FDA has approved Idvynso (doravirine/islatravir, DOR/ISL) dual-drug, single-tablet regimen for the treatment of HIV-1 infection in adults as an alternative to current antiretroviral therapy. The indication is for patients who have achieved virological suppression (HIV-1 RNA below 50 copies/mL) on a stable antiretroviral therapy regimen, have no history of virological treatment failure, and have no known substitutional mutations associated with DOR resistance.

This approval is primarily based on week 48 data from two pivotal Phase 3 clinical trials (MK-8591A-051 and MK-8591A-052). In the double-blind MK-8591A-052 trial, the primary endpoint (HIV-1 RNA ≥50 copies/mL) showed that at week 48, 1% (n=342) of participants who switched to Idvynso had a viral load ≥50 copies/mL, compared to 1% (n=171) of participants who continued with the active control drug BIC/FTC/TAF. The secondary endpoint at week 48 showed that 92% of participants who switched to Idvynso maintained virological suppression (HIV-1 RNA <50 copies/mL), compared to 94% of participants who continued with the active control drug.

In the open-label MK-8591A-051 trial, the primary endpoint (HIV-1 RNA ≥50 copies/mL) showed that at week 48, 1% (n=366) of participants who switched to Idvynso had a viral load ≥50 copies/mL, compared to 5% (n=185) of participants who continued basic antiretroviral therapy (bART) . The secondary endpoint at week 48 showed that 96% of participants who switched to Idvynso maintained virological suppression (HIV-1 RNA <50 copies/mL), compared to 92% of participants who continued bART .

In both trials, the overall safety profile of Idvynso was comparable to that of the respective active control drugs. In the MK-8591A-052 trial, by week 48, 3% of participants in the Idvynso group and 2% in the active control group discontinued the study drug due to adverse events. In the MK-8591A-051 trial, by week 48, 0.5% of participants in the Idvynso group and 2% in the bART group discontinued the study drug due to adverse events. Furthermore, in participants aged 65 years and older treated with Idvynso in both trials, no difference in overall safety or efficacy was observed compared to younger participants; however, the possibility of higher sensitivity in some older individuals cannot be ruled out.

As of week 48, the most common adverse events (all grades) in both trials were as follows:

•
The MK-8591A-052 trial (Idvynso group vs. active control drug group): diarrhea (1% vs 1%), dizziness (1% vs 0%), fatigue (1% vs 1%), abdominal distension (1% vs 0%), headache (1% vs 0%), and weight gain (less than 1% vs 0%).
•
•
MK-8591A-051 trial (Idvynso group vs bART group): diarrhea (3% vs 0%), dizziness (2% vs 1%), fatigue (2% vs 1%), bloating (2% vs 0%), headache (2% vs 1%), weight gain (2% vs 0%).
•

Doravirine is an oral non-nucleoside reverse transcriptase inhibitor. It works by binding to the reverse transcriptase of the HIV-1 virus, preventing the virus from converting RNA into DNA, thereby blocking HIV-1 replication. It is approved in the United States for the treatment of HIV-1-infected adults who have not received antiretroviral therapy. Islatravir, on the other hand, is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) with both transcriptase and translocation inhibition (preventing nucleotide binding and incorporation into the DNA chain, leading to immediate chain termination) and delayed chain termination (preventing nucleotide incorporation even in the event of translocation).

https://mp.weixin.qq.com/s/EmTOvKWEw1t3oNAITwXNTw