Lenacapavir moves forward
Lenacapavir is an experimental drug being developed for at least the following uses:
- combination therapy for people who have multidrug-resistant HIV
- to reduce the risk of acquiring HIV
About lenacapavir
Lenacapavir is different from all other approved anti-HIV drugs. It belongs to a new class of drugs called capsid inhibitors. This class of drugs target capsid proteins.
Here is the role of capsid proteins in HIV infection:
When HIV enters a cell, the capsid protein acts as a shell protecting HIV’s genetic information from the cell’s viral sensors and defence system. The capsid also helps to transport the virus’ genetic information to the cell’s control centre, or nucleus. As it nears the nucleus, the capsid releases HIV’s genetic information so that it can insert itself into the cell’s genetic information. Once this has happened, HIV usually takes over the cell, forcing it to become a mini-virus factory. The infected cell produces new copies of HIV.
If the capsid protein is absent or defective, HIV cannot infect a target cell.
Enter lenacapavir
Lenacapavir (formerly GS-6207) is the first capsid inhibitor that is being developed for use against HIV. It is currently in phase III clinical trials, where it is being tested as part of a treatment for people with multidrug-resistant HIV. It is also being tested in other clinical trials as a form of HIV prevention.
Lenacapavir comes in two formulations—tablets and a liquid. People initiating lenacapavir first take the tablet formulation. This raises concentrations of lenacapavir in the blood. After a couple of weeks, people can then decide whether they want to continue taking oral lenacapavir or switch to the liquid formulation, which is injected just under the skin (subcutaneous injection). If they continue with the tablets, they can do so at a reduced frequency of once weekly, as the drug levels have built up. With the liquid formulation, once lenacapavir has been injected, it is gradually released into circulation. Lenacapavir has been designed to break down slowly. All of these properties—gradual release from subcutaneous tissue and its slow breakdown—mean that lenacapavir need only be injected once every six months.
A temporary stop
In December 2021, trials of injectable lenacapavir were halted because of an issue with the glass vials that were used to package the liquid. It appeared that in some cases tiny particles of glass entered the lenacapavir solution.
Gilead has investigated the issue and changed the formulation of the vials. The U.S. Food and Drug Administration (FDA) has since allowed trials of injectable lenacapavir to resume.
—Sean R. Hosein
REFERENCES:
- Segal-Maurer S, DeJesus E, Stellbrink HJ, et al. Capsid inhibition with lenacapavir in multidrug-resistant HIV-1 infection. New England Journal of Medicine. 2022 May 12;386(19):1793-1803.
- Marrazzo J. Lenacapavir for HIV-1 – Potential promise of a long-acting antiretroviral drug. New England Journal of Medicine. 2022 May 12;386(19):1848-1849.
- Gilead Sciences. FDA Lifts Clinical Hold on Investigational Lenacapavir for the Treatment and Prevention of HIV. Press release. 16 May 2022.