Gilead and MSD to progress weekly HIV treatment to Phase III

Gilead Sciences and MSD are progressing their once-weekly HIV treatment regimen to Phase II trials after receiving positive results from a 48-week study. This innovative treatment merges MSD’s investigational drug islatravir, a nucleoside reverse transcriptase inhibitor, with Gilead’s lenacapavir, sold under the brand name Sunlenca for use alongside other antiretroviral medications in treating patients with multidrug-resistant HIV. Unlike the currently available daily HIV treatments, such as Gilead's Biktarvy (containing bictegravir, emtricitabine, and tenofovir alafenamide), this new regimen offers a long-acting alternative for individuals living with HIV.

In the Phase II clinical trial (NCT05052996), 104 virologically suppressed adults previously on Biktarvy were randomly selected either to continue their daily treatment or switch to the once-weekly islatravir/lenacapavir combination. At the 24-week milestone, 94.2% of patients on the experimental combination maintained viral loads below 50 copies per milliliter, a crucial parameter for HIV suppression, which was comparable to the results of the Biktarvy group. By week 48, the new regimen sustained its efficacy, with 94.2% of participants achieving ongoing viral suppression, versus 92.4% of those who remained on Biktarvy.

These findings indicate that the once-weekly combination could provide a more convenient option for patients, potentially reducing the challenges associated with daily medication. Currently, the only long-acting HIV treatment approved in the US is Viiv Healthcare’s Cabenuva, which is administered as monthly or bi-monthly injections. Consequently, Gilead and MSD’s new oral regimen might become an appealing alternative for those seeking less frequent dosing.

Biktarvy, approved for once-daily administration to treat certain types of HIV, generated $11.9 billion in global sales in 2023, according to Gilead’s financial reports. GlobalData’s Pharma Intelligence Center projects that Biktarvy will generate $15.3 billion in sales by 2030.

In the announcement of the trial results, Elizabeth Rhee, vice president of global clinical development at Merck Research Laboratories, remarked that daily single-tablet regimens have revolutionized HIV care but can be difficult for some patients to maintain. Novel treatment options that permit less frequent oral dosing may help improve adherence and address the stigma some individuals face with daily oral therapy.

MSD previously attempted to develop a higher dose of islatravir, but had to halt development after it caused a decrease in lymphocyte and CD4+ T cell counts in clinical trials in 2021. However, in the current Phase II study by MSD and Gilead, no significant differences in immune cell counts were observed between the Biktarvy and experimental groups. Furthermore, no participants discontinued the trial due to reduced CD4+ T-cell or lymphocyte counts. Buoyed by these promising results, Gilead and MSD are moving forward to Phase III trials for this treatment.

In addition to this combination therapy, Gilead is also progressing lenacapavir as a pre-exposure prophylaxis (PrEP) treatment, a category of drugs that HIV-negative individuals can take to reduce their risk of contracting HIV. The company plans to utilize data from two Phase III clinical trials – PURPOSE-1 (NCT04994509) and PURPOSE-2 (NCT04925752) – to support global regulatory submissions for lenacapavir for PrEP, expected to commence by the end of 2024.