Gilead, MSD say HIV combo could be weekly, oral HIV drug

In a phase 2 trial, an antiretroviral combination developed by Gilead Sciences and MSD suppressed HIV with a single weekly oral dose, raising the hope of a new treatment option for patients.

The new data – presented at the IDWeek congress yesterday – found that the pairing of MSD's experimental nucleoside reverse transcriptase translocation inhibitor islatravir with Gilead's already-marketed capsid inhibitor Sunlenca (lenacapavir) was able to maintain viral suppression over 48 weeks of follow-up.

It follows 24-week results reported earlier this year and means that the new regimen will now advance into a phase 3 programme, said Gilead and MSD, known as Merck & Co in the US and Canada.

Patients in the study were switched to the regimen after being well-maintained on current antiretroviral therapy (ART) based on daily oral doses of Gilead's Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide).

At the 24-week timepoint, 94.2% of the islatravir/lenacapavir regimen still had copies below 50 copies per ml, the limit of detection, which was the same proportion as a group that continued on Biktarvy. New data at 48 weeks – a secondary endpoint – showed that level of efficacy was achieved in 94.2% and 92.3% of patients, respectively, showing the experimental therapy was non-inferior.

While there was some missing data in the study, no patients on Gilead and MSD's regimen had levels above the 50 copies/ml threshold, compared to 1.9% of the Biktarvy group.

"Daily single-tablet regimens have helped to transform HIV care but can be challenging for some people to maintain," said Dr Elizabeth Rhee, head of Merck Research Laboratories.

"Novel HIV treatment options that allow for less frequent oral dosing have the potential to help support adherence, and address stigma faced by some individuals taking daily oral therapy," she added.

A less frequent oral option could complement other new products designed to improve compliance with ART, including long-acting injectable products that release drugs over weeks or months.

Those include Sunlenca, which is approved for resistant HIV as a twice-yearly injection after an initial oral regimen, and ViiV Healthcare's Cabenuva (cabotegravir/rilpivirine), which is administered every one or two months without lead-in oral dosing.

Islatravir/lenacapavir could provide an additional option for patients reluctant to have injections, but wishing to break free of the bind of taking tablets every day.

MSD was originally developing a much higher dose of islatravir as a once-monthly oral regimen for pre-exposure prophylaxis (PrEP), but discontinued the programme after two phase 3 trials revealed it was reducing levels of CD4-positive T cells.

It remains in phase 3 as a once-daily oral regimen given alongside the company's non-nucleoside reverse transcriptase inhibitor (NNRTI) Pifeltro (doravirine), which was approved by the FDA in 2019.