In those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of virologic treatment failure and no known substitutions associated with resistance to doravirine. IDVYNSO is contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers and lamivudine (3TC) or emtricitabine (FTC). Co-administration with these drugs may decrease the effectiveness of IDVYNSO. See additional selected safety information on the following pages. IDVYNSO (pronounced ihd-VIHN-soh) will be available in pharmacies after May 11.
“Advances in HIV treatment mean more people living with HIV are living longer — a remarkable achievement,” said Carl Baloney, Jr., president and chief executive officer of AIDS United. “People aging with HIV face additional health challenges, including managing multiple chronic conditions and medications at the same time. It is essential that management of HIV considers these factors in addition to virologic suppression when choosing an HIV treatment regimen.”
“IDVYNSO combines islatravir, a next-generation NRTI with multiple mechanisms of action, including translocation inhibition, with doravirine, an NNRTI with an established efficacy and safety profile. As the only two-drug, non-INSTI, tenofovir-free regimen, IDVYNSO expands therapeutic diversity beyond the currently available oral treatment options,” said Dr. Eliav Barr, senior vice president and chief medical officer, Merck Research Laboratories. “As the health needs of adults living with HIV change over time, IDVYNSO gives clinicians a new choice for HIV treatment. This approval marks an important new chapter in Merck’s long-standing commitment to research and discovery for people living with HIV.”
IDVYNSO is a complete regimen; co-administration with other antiretroviral medications for treatment of HIV-1 infection is not recommended. Severe skin reactions, including Stevens-Johnson syndrome/toxic epidermal necrolysis, have been reported with doravirine-containing regimens. Drug Rash with Eosinophilia and Systemic Symptoms was reported with IDVYNSO. Concomitant use of IDVYNSO and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect of IDVYNSO and possible development of resistance, or possible clinically significant adverse reactions from greater exposures of a component of IDVYNSO. See additional selected safety information on the following pages.
“IDVYNSO is the first non-INSTI, tenofovir-free, two-drug regimen to demonstrate non-inferior efficacy to standard oral antiretroviral regimens, including BIKTARVY. This makes IDVYNSO a potential alternative for people with virologically suppressed HIV who may need to switch their treatment,” said Dr. Amy Colson, director of research at Community Resource Initiative, Boston, Massachusetts.
Phase 3 studies supporting approval of IDVYNSO
The efficacy and safety of IDVYNSO is supported by Week 48 data from two randomized, active-controlled, non-inferiority trials [Trial 052 (NCT05630755) and Trial 051 (NCT05631093)] in virologically-suppressed (HIV-1 RNA less than 50 copies per mL) adults living with HIV. Participants must have been stably suppressed on their baseline regimen for at least 3 months prior to trial entry and had no history of treatment failure. Across the two trials, a total of 708 participants received once-daily IDVYNSO; of these, 81 (11%) participants were aged 65 years and older, including 10 (1%) aged 75 years and older.
In the double-blind Trial 052, participants were switched from BIKTARVY [bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF)] to IDVYNSO. A total of 513 participants were randomized (2:1) and were switched to once-daily IDVYNSO (n=342) or remained on BIC/FTC/TAF (n=171). At baseline, participants had a mean age of 48 years (range: 19 to 77), 21% of participants were female, 61% were White, 31% were Black/African American, and 6% were Asian. A total of 23% identified as Hispanic/Latino.
In the open-label Trial 051, participants were switched from an oral ART (antiretroviral therapy) regimen to IDVYNSO. A total of 551 participants were randomized (2:1) and were switched to once-daily IDVYNSO (n=366) or remained on their baseline ART (bART) (n=185). Randomization was stratified by bART. At baseline, participants had a mean age of 50 years (range: 18 to 83), 40% of participants were female, 39% were White, 45% were Black/African American, and 5% were Asian. A total of 15% identified as Hispanic/Latino. At enrollment, 64% of the participants were receiving integrase strand transfer inhibitor (INSTI)-based regimens, 5% protease inhibitor (PI)-based regimens (including combinations with INSTI), and 30% were receiving other regimens.
Efficacy profile of IDVYNSO
IDVYNSO was non-inferior to BIC/FTC/TAF (in Trial 052) and bART (in Trial 051) as assessed by the proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48.
In the double-blind Trial 052, results for the primary endpoint (HIV-1 RNA ≥50 copies/mL) showed that 1% of participants who were switched to IDVYNSO (n=342) had a viral load of ≥50 copies/mL at Week 48, compared to 1% who continued on BIC/FTC/TAF (n=171; treatment difference 0.9%, 95% CI, -1.9%, 2.9%). At Week 48, results from the secondary endpoint showed that 92% of participants who switched to IDVYNSO maintained viral suppression (HIV-1 RNA <50 copies/mL) compared to 94% of participants who continued receiving BIC/FTC/TAF.
In the open-label Trial 051, results for the primary endpoint (HIV-1 RNA ≥50 copies/mL) showed that 1% of participants who were switched to IDVYNSO (n=366) had a viral load of ≥50 copies/mL at Week 48, compared to 5% who continued on bART (n=185; treatment difference -3.6%, 95% CI, -7.8%, -0.8%). At Week 48, results from the secondary endpoint showed that 96% of participants who switched to IDVYNSO maintained viral suppression (HIV-1 RNA <50 copies/mL) compared to 92% of participants who continued on bART.
In both trials, treatment outcomes between treatment groups were similar across subgroups by age, sex and race, and in Trial 051, also by bART regimens. In participants aged 65 years and older who received IDVYNSO in both trials, no overall differences in safety or effectiveness were observed between these participants and younger participants, but greater sensitivity of some older individuals cannot be ruled out.
Safety and tolerability profile of IDVYNSO
The safety profile of IDVYNSO was generally comparable to BIC/FTC/TAF in Trial 052 and to oral bART regimens in Trial 051. In Trial 052, by Week 48, 3% in the IDVYNSO group and 2% in the BIC/FTC/TAF group had adverse events leading to discontinuation of study medication. In Trial 051, by Week 48, 0.5% in the IDVYNSO group and 2% in the bART group had adverse events leading to discontinuation of study medication.
The most common adverse reactions (all grades) reported in greater than or equal to 2% of participants in any treatment group in Trials 052 and 051 through Week 48 were as follows:
- In Trial 052 (IDVYNSO vs BIC/FTC/TAF, respectively): diarrhea (1% vs 1%), dizziness (1% vs 0%), fatigue (1% vs 1%), abdominal distention (1% vs 0%), headache (1% vs 0%), weight increase (less than 1% vs 0%).
- In Trial 051 (IDVYNSO vs bART, respectively): diarrhea (3% vs 0%), dizziness (2% vs 1%), fatigue (2% vs 1%), abdominal distention (2% vs 0%), headache (2% vs 1%), weight increase (2% vs 0%).
Trial participants taking IDVYNSO had minimal change in weight from baseline. The mean change in weight from baseline at Week 48 was -0.03 kg in the IDVYNSO group vs. 0.28 kg in the BIC/FTC/TAF group in Trial 052 and 0.94 kg in the IDVYNSO group vs. -0.15 kg in the bART group in Trial 051. Four of the six participants with adverse reactions of weight increased switched from a bART regimen containing efavirenz and/or tenofovir disoproxil fumarate in Trial 051.
The Merck Access Program for IDVYNSO
Merck offers support to individuals who are prescribed IDVYNSO, including information about individual insurance coverage and out-of-pocket costs, co-pay assistance for eligible, commercially insured individuals, and how individuals may access IDVYNSO through The Merck Access Program.
About IDVYNSO
IDVYNSO is a fixed-dose combination of two medicines, doravirine with islatravir. Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase. Islatravir is a potent, next-generation nucleoside analog reverse transcriptase inhibitor (NRTI) that blocks HIV-1 replication by multiple mechanisms including:
inhibition of reverse transcriptase translocation, resulting in immediate chain termination, and
induction of structural changes in the viral DNA (delayed chain termination).
Merck’s Commitment to HIV
For 40 years, Merck has been committed to scientific research and discovery in HIV leading to scientific breakthroughs that have helped change HIV treatment. Our work has helped pioneer the development of new options across multiple drug classes to help those impacted by HIV. Today, we are developing a series of antiviral options designed to help people manage HIV and protect people from HIV. We are researching for real life and want to ensure people are not defined by HIV. Our work focuses on transformational innovations, collaborations with others in the global HIV community and access initiatives aimed at helping to end the HIV epidemic for everyone.
About Merck’s HIV research
Islatravir is under evaluation in multiple ongoing early and late-stage clinical trials in combination with other antiretrovirals for potential once-weekly treatments for HIV-1, with islatravir serving as the anchor medicine in these two-drug regimens. Islatravir in combination with Gilead’s lenacapavir is in Phase 3 development as a novel oral once-weekly treatment for HIV-1 [ISLEND-1 (NCT06630286) and ISLEND-2 (NCT06630299)], and islatravir in combination with our company’s investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) ulonivirine (MK-8507) is in Phase 2b development [MK-8591B-060 (NCT06891066) and MK-8591B-062 (NCT07266831)] as an oral once-weekly treatment.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities.
For more information, please visit www.merck.com
