Drug name
Last update: Aug 2026MK-8591D (Islatravir and Lenacapavir)
Developer(s)
Drug information
MK-8591D (islatravir and lenacapavir fixed dose combination)
Not provided
Small molecule
NRTTI + capsid inhibitor
Islatravir and Lenacapavir (ISL+LEN) is an investigational drug combination currently in clinical development for the treatment of HIV-1. Islatravir (MK-8591) is a nucleoside reverse transcriptase translocation inhibitor under evaluation in several ongoing clinical trials. Lenacapavir is a first in-class HIV-1 capsid inhibitor also being studied as a potential long-acting option in multiple ongoing studies for HIV treatment. The ISL+LEN combination is a proposed once-weekly oral fixed-dose combination regimen consisting of ISL 2mg and LEN 300mg. Once-weekly dosing has the potential to address adherence challenges versus daily oral ART. The pharmacokinetic profiles and potent antiviral activities of both ISL and LEN support their continued development as an investigational drug combination.
Islatravir and lenacapavir (ISL+LEN) is an investigational drug combination and is not currently approved in any jurisdiction globally. The safety and efficacy of the ISL+LEN combination has not yet been established. Pivotal studies are ongoing (Phase III ISLEND-1 and ISLEND-2 studies of lenacapavir/islatravir for the treatment of virally suppressed PLHIV)
In March 2021, Gilead Sciences and Merck announced that they have entered into an agreement to co-develop and co-commercialize long-acting treatments in HIV that combine Gilead’s investigational capsid inhibitor, lenacapavir, and Merck’s investigational nucleoside reverse transcriptase translocation inhibitor, islatravir, into a two-drug regimen with the potential to provide new treatment options for people living with HIV. Gilead Sciences anticipates a commercial launch of lenacapavir + islatravir for the treatment of HIV in 2027.
Therapeutic area(s)
- HIV
- Treatment
Administration route
Oral
Associated long-acting platforms
Oral solid form
Use of drug
- Self-administered
- Weekly
Dosage
fixed dose combination of 300 mg lenacapavir + 2 mg islatravir
Not provided
investigational dose used in pivotal clinical trials is once weekly oral fixed dose combination tablet containing 300 mg lenacapavir + 2 mg islatravir
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Associated compounds, formulations and regimens
Islatravir (ISL)
Lenacapavir (LEN)
Associated technologies
Not provided
Additional information
Developer(s)
Merck / MSD
Merck & Co., Inc. is an American multinational pharmaceutical company known as Merck Sharp & Drone (MSD) in territories outside of the USA and Canada. Merck was originally established in 1891, and is headquartered in Rahway, New Jersey. The company is particularly well known for developing and manufacturing biologic therapies, vaccines, medicines and animal health products.
Gilead
Gilead Sciences, Inc. is a multinational biopharmaceutical company that develops and manufactures innovative medicines for life-threatening diseases, including anti-viral therapeutics for HIV/AIDS, Hepatitis B, Hepatitis C and Covid-19. Headquartered in Foster City, California, Gilead was originally founded in 1987 and is currently listed on both the S&P 500 and the NASDAQ Biotechnology Index.
Drug structure
Scale-up and manufacturing prospects
Lenacapavir is commercially manufactured by Gilead Sciences. Several synthetic chemical processes describing the manufacture of islatravir (ISL) have been published. However, these approaches have proved to be complex and highly inefficient, with marked difficulty in controlling 2’-deoxyribonucleoside anomer stereochemistry and the requirement for several protecting-group manipulations. To counter these issues, Merck developed a highly innovative and extraordinarily efficient approach utilising directed evolution to create a novel three-step biocatalytic cascade for ISL synthesis.
Islatravir: EasyMax 102 and 402 equipped with FireStringO2 sensors and the EasySampler 1210 system. A thermal gas flow controller (Aalborg, USA) to monitor and control oxidation air-gas flow to the reactor, with a suitable compressed air-source. Lenacapavir: Stainless steel pharmaceutical reactors, glass-lined reactors, rotary evaporator (rotovap), flash chromatography columns, stainless steel autoclave, cooling bath, silica gel chromatography columns, vacuum distillation apparatus, simulated moving bed chromatography system, Chiralpak columns.
For Islatravir synthesis, the automated lab reactor platforms EasyMax 102 and 402 (Mettler-Toledo AG, AutoChem, Switzerland) were utilised by Merck for reaction scale-up. Although ISL+LEN is currently being evaluated as a fixed-dose oral regimen, future studies may permit LEN to be administered via subcutaneous injection. In this instance, storage of injectable lenacapavir in borosilicate vials is contraindicated due to issues with chemical compatibility. Instead, it is recommended that vials are made from aluminosilicate glass.
Islatravir: 400 MHz Briker AVANCE III and 500MHz Bruker Ultrashield spectrometer (or equivalent) for 1H, 19F, 31P and 13C NMR. An Accurate-Mass Time-of-Flight (TOF) high resolution mass spectrometer. Molecular Devices plate reader Spectra Max Plus for Spectrophotomeric analyses, alongside a Perkin Elmer polarimeter with a PCB 1500 water Peltier system for optical rotation measurements. Lenacapavir: Proton nuclear magnetic resonance (1H NMR), High-performance liquid chromatography (HPLC), Ultra-Performance Liquid Chromatography (UPLC).
Excipients & delivery device(s)
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No delivery device
Safety, Efficacy and Evidence Summary
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