doravirine/islatravir (MK-8591A) / Merck (MSD) - LARVOL DELTA

U.S. FDA Accepts New Drug Application for Merck’s Doravirine/Islatravir, an Investigational, Once-Daily, Oral, Two-Drug Regimen for Treatment of Adults with Virologically Suppressed HIV-1 Infection (Businesswire) - "Merck...announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for doravirine/islatravir (DOR/ISL), an investigational, once-daily, oral, two-drug regimen for adults with HIV-1 infection that is virologically suppressed on antiretroviral therapy. The FDA has set a target action date of April 28, 2026, for the application under the Prescription Drug User Fee Act (PDUFA)...The NDA is based on findings at Week 48 of two pivotal Phase 3 clinical trials (MK-8591A-051 and MK-8591A-052)..."

FDA filing • PDUFA • Human Immunodeficiency Virus • Infectious Disease

Evaluation of Fasting Lipids and Insulin Resistance After Switch to Doravirine/Islatravir (100 mg/0.25 mg) Once Daily: Week 48 Results From Two Randomized Phase 3 Studies in Adults Living With HIV-1 (EACS 2025) - No abstract available

Clinical • P3 data • Human Immunodeficiency Virus • Infectious Disease

Switching to Doravirine/Islatravir (100 mg/0.25 mg) once daily maintained viral suppression in the presence of archived M184I/V resistance-associated mutations in proviral DNA (IAS-HIV 2025) - P3 | "BACKGROUND: In three Phase 3 studies (P051: NCT05631093; P052: NCT05630755; P054: NCT05766501) virologic suppression was maintained in people living with HIV who switched to doravirine/islatravir (DOR/ISL 100 mg/0.25 mg); 2 studies (P051 and P052) were comparative and demonstrated noninferiority to baseline antiretroviral therapy (bART) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Switching to DOR/ISL 100 mg/0.25 mg in Phase 3 clinical studies maintained viral suppression for at least 48 weeks in the presence of preexisting M184I/V in proviral DNA."

Human Immunodeficiency Virus • Infectious Disease

A Study of Doravirine/Islatravir in Healthy Lactating Females (MK-8591A-061) (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1 trial

Open-label, Follow-up of Doravirine/Islatravir (DOR/ISL 100 mg/0.75mg) for Participants With Human Immunodeficiency Virus-1 (HIV-1) Infection (MK-8591A-033) (clinicaltrials.gov) - P3 | N=2000 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2027 ➔ May 2028 | Trial primary completion date: Oct 2027 ➔ May 2028

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Weight and Body Composition After Switch to Doravirine/Islatravir (100 mg/0.25 mg) Once Daily from BIC/FTC/TAF in Adults Living With HIV-1: Week 48 Results From a Randomized, Double-Blind Phase 3 Study (EACS 2025) - No abstract available

Clinical • P3 data • Human Immunodeficiency Virus • Infectious Disease

Combined doravirine and islatravir cooperate to inhibit NRTI and NNRTI resistant HIV-1 in vitro. (PubMed, Antiviral Res) - "MuSyC scores showed a negative correlation with doravirine FC values, number of NRTI mutations and presence of M184V/I, but not with islatravir FC values. Doravirine and islatravir may cooperatively inhibit NRTI and NNRTI resistant viruses despite complex mutational profiles, however the accumulation of resistance mutations may reduce the combinatorial activity."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease

Switch to Doravirine/Islatravir (DOR/ISL) in Human Immunodeficiency Virus 1 (HIV-1) Participants Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-018) (clinicaltrials.gov) - P3 | N=643 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

Switch to DOR/ISL (100/0.25 mg) QD From Oral ART: An Open-Label Phase III Study in Adults With HIV-1 (CROI 2025) - P3 | "MK-8591A-051 is a phase 3 study evaluating the efficacy and safety of switching from oral ART to DOR/ISL (100/0.25 mg), a once-daily single-tablet regimen...Conclusions Switching to DOR/ISL (100/0.25 mg) maintained viral suppression and was non-inferior to continuing bART at week 48. DOR/ISL was well tolerated with a similar safety profile to bART and did not adversely affect lymphocytes."

Clinical • Late-breaking abstract • P3 data • Human Immunodeficiency Virus • Infectious Disease • CD4

Switch to DOR/ISL (100/0.25 mg) QD From BIC/FTC/TAF: A Blinded Phase III Study in Adults With HIV-1 (CROI 2025) - P3 | "MK-8591A-052 is an ongoing phase 3 study evaluating the efficacy and safety of switching from bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) to DOR/ISL (100/0.25 mg), a once-daily single-tablet regimen. Conclusions DOR/ISL (100/0.25 mg) maintained viral suppression and was non-inferior to BIC/FTC/TAF at week 48. DOR/ISL was well tolerated with a similar safety profile to BIC/FTC/TAF and did not adversely affect lymphocytes."

Clinical • Late-breaking abstract • P3 data • Human Immunodeficiency Virus • Infectious Disease • CD4

Doravirine/islatravir (100/0.75 mg) once-daily compared to bictegravir/emtricitabine/tenofovir alafenamide as initial HIV-1 treatment: 48-week results from a phase 3, randomized, controlled, double-blind, non-inferiority trial. (PubMed, Clin Infect Dis) - P3 | "Doravirine/islatravir (100/0.75 mg) once-daily was non-inferior to bictegravir/emtricitabine/tenofovir alafenamide through week 48 for initial HIV-1 treatment. Due to decreases in CD4 and lymphocyte counts, development of this dose of doravirine/islatravir was stopped."

Head-to-Head • Journal • P3 data • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease • CD4

Study of Doravirine/Islatravir (DOR/ISL 100 mg/0.75 mg) to Evaluate the Antiretroviral Activity, Safety, and Tolerability in Treatment-Naïve Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-020) (clinicaltrials.gov) - P3 | N=599 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

Doravirine/Islatravir for the treatment of HIV. (PubMed, Expert Opin Pharmacother) - "ISL doses as low as 0.25 mg proved non-inferior to current treatments. Therefore, evaluation of the long-term efficacy and safety of DOR/ISL should focus on reduced doses of ISL and minimizing CD4 reduction."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • CD4

A Study of Doravirine and Islatravir as a Single Entity or Combination Therapy and the Effect of Food in Healthy Adult Participants (MK-8591A-055) (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Merck Sharp & Dohme LLC

Combination therapy • New P1 trial

DOR/ISL in HIV-1 Antiretroviral Treatment-naïve Participants (MK-8591A-053) (clinicaltrials.gov) - P3 | N=500 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease

Safety and Efficacy of a Switch to Doravirine/Islatravir in Participants With HIV-1 (MK-8591A-017) (clinicaltrials.gov) - P3 | N=672 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

The Effect of Pantoprazole on Doravirine/Islatravir Pharmacokinetics (IDWeek 2024) - No abstract available

PK/PD data • Infectious Disease

DOR/ISL in HIV-1 Antiretroviral Treatment-naïve Participants (MK-8591A-053) (clinicaltrials.gov) - P3 | N=500 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Nov 2026 ➔ Aug 2029

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

A Study of Doravirine/Islatravir (DOR/ISL, MK-8591A) for the Treatment of Human Immunodeficiency Virus 1 (HIV-1) Infection in Participants Who Previously Received DOR/ISL (MK-8591A-054) (clinicaltrials.gov) - P3 | N=650 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Jan 2026 ➔ Sep 2028

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-052) (clinicaltrials.gov) - P3 | N=514 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2025 ➔ Aug 2028

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Antiretroviral Therapy (ART) (MK-8591A-051) (clinicaltrials.gov) - P3 | N=501 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2025 ➔ Jul 2028

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

Challenges for novel antiretroviral development in an era of widespread TLD availability. (PubMed, Clin Infect Dis) - "We illustrate when generic TLD will become available worldwide and compare this with trial programmes and approval timelines for two case-study novel ART combinations: islatravir/doravirine and cabotegravir/rilpivirine. We demonstrate that currently these regimens and trial programmes will not meet key benchmarks required to compete with TLD."

Journal • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation

Switch to fixed-dose doravirine (100 mg) with islatravir (0·75 mg) once daily in virologically suppressed adults with HIV-1 on antiretroviral therapy: 48-week results of a phase 3, randomised, open-label, non-inferiority trial. (PubMed, Lancet HIV) - P3 | "Switching to single-tablet doravirine (100 mg) and islatravir (0·75 mg) maintained viral suppression up to week 48 and was non-inferior to antiretroviral combinations used in clinical practice for adults with HIV-1; however, decreases in CD4 cell and total lymphocyte counts do not support further development of once-daily doravirine (100 mg) and islatravir (0·75 mg)."

Head-to-Head • Journal • P3 data • Human Immunodeficiency Virus • Infectious Disease • Pain • CD4

Switch to fixed-dose doravirine (100 mg) with islatravir (0·75 mg) once daily in virologically suppressed adults with HIV-1 on bictegravir, emtricitabine, and tenofovir alafenamide: 48-week results of a phase 3, randomised, controlled, double-blind, non-inferiority trial. (PubMed, Lancet HIV) - P3 | "Switching to daily doravirine (100 mg) and islatravir (0·75 mg) was non-inferior to bictegravir, emtricitabine, and tenofovir alafenamide at week 48. However, decreases in CD4 cell and total lymphocyte counts do not support the further development of once-daily doravirine (100 mg) and islatravir (0·75 mg)."

Head-to-Head • Journal • P3 data • Human Immunodeficiency Virus • Infectious Disease • Pain • CD4

Safety and Efficacy of a Switch to Doravirine/Islatravir in Participants With HIV-1 (MK-8591A-017) (clinicaltrials.gov) - P3 | N=672 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Mar 2024 ➔ Nov 2024

Trial completion date • Human Immunodeficiency Virus • Infectious Disease