Lenacapavir – an emerging drug for HIV treatment and hopefully prevention

Lenacapavir is an emerging anti-HIV drug. It works by interfering with an HIV protein called the capsid. Lenacapavir therefore belongs to an emerging group of HIV drugs called capsid inhibitors.

Lenacapavir was first approved for use by authorities in the European Union and has recently been approved by Health Canada. Lenacapavir is meant to be used as part of combination therapy for people who have HIV that is resistant to many treatments. Researchers refer to this group of people as “heavily treatment-experienced.”

Lenacapavir is meant to first be taken as a pill three times over the course of eight days. About a week after the third (and final) oral dose, nurses administer two subcutaneous (just under the skin) injections of lenacapavir in the belly. After these initial injections, additional injections are administered every 26 weeks (roughly every six months). Lenacapavir is meant to be taken as part of combination treatment, so people using it will also have to take other HIV drugs (as daily pills). Lenacapavir must be taken with other anti-HIV drugs to have maximal effect against the virus.

Lenacapavir has been tested in a clinical trial with 72 people who had HIV with extensive resistance to other treatments. Prior to using lenacapavir, and while taking other HIV treatments, many of these people had detectable viral loads (on average around 15,000 copies/mL). Fourteen people had a viral load greater than 100,000 copies/mL. Prior to the participants taking lenacapavir, technicians performed resistance test analyses of their blood samples. This was done to assess the degree of HIV’s ability to resist the effect of treatment. Based on the results of resistance testing, participants’ regimens were adjusted and lenacapavir was added.

After six months, 82% of participants achieved and maintained a suppressed viral load. Limited data suggested that viral suppression persisted for many people in the study after one year.

Lenacapavir and islatravir

Lenacapavir will be tested in a clinical trial with the experimental drug islatravir (mentioned earlier in this issue of TreatmentUpdate). In that trial both drugs will be given once weekly.

Lenacapavir as PrEP

Lenacapavir is also being tested in large studies to assess its effectiveness for the prevention of HIV—pre-exposure prophylaxis (PrEP). If the trials show that lenacapavir is highly effective, its developer, Gilead Sciences, will hopefully seek to have it approved for PrEP. Such approval is first likely in the U.S. As the trials are still underway, lenacapavir may not be approved for PrEP until 2025.

—Sean R. Hosein

REFERENCES:

1. Gilead Sciences. Gilead announces first global regulatory approval of Sunlenca® (lenacapavir), the only twice-yearly HIV treatment option. Press release. 22 August 2022.
2. Gilead Sciences. FDA lifts clinical hold on investigational lenacapavir for the treatment and prevention of HIV: All clinical studies evaluating injectable lenacapavir to resume; decision based on review of vial compatibility data. Press release. 16 May 2022.
3. Gilead Sciences. Gilead and Merck announce temporary pause in enrollment for phase 2 study evaluating an oral weekly combination regimen of investigational islatravir and investigational lenacapavir. Press release. 23 November 2021.