Gilead, Merck's long-acting HIV treatment enters Phase 3

In a notable collaboration between two pharmaceutical giants, Gilead Sciences and Merck have announced promising results from a 48-week study on their experimental once-weekly HIV treatment pill. This new regimen, which combines Merck’s islatravir and Gilead's lenacapavir (marketed as Sunlenca for certain HIV patients), demonstrated similar viral suppression levels compared to the conventional daily therapy. Presently, HIV medications require daily administration, but the innovation behind this experimental drug aims to offer a long-acting oral option for those living with HIV. This comes in addition to the already existing long-acting injectable option, ViiV’s Cabenuva, which is administered either monthly or every two months.

Jared Baeten, Gilead’s head of the virology therapeutic area, highlighted the need for more flexible treatment options. He noted that while daily therapies are effective and well-tolerated by many, they are not suitable for everyone. The new once-weekly pill could potentially address this gap, providing more convenience and possibly improving adherence among patients.

The Phase 2 open-label study involved 104 adults who were previously on Gilead’s Biktarvy, a daily regimen combining three HIV medications. Participants were randomized to either continue with Biktarvy or switch to the experimental combination of islatravir and lenacapavir. After 48 weeks, the group on the new regimen achieved a 94.2% rate of viral suppression, slightly higher than the 92.3% observed in the Biktarvy group. Importantly, no participants in either group had a viral load of 50 copies/mL or more, a common benchmark for measuring HIV viral load.

The experimental drugs work through different mechanisms to inhibit the virus. Lenacapavir disrupts the virus's protective shell, while islatravir blocks the reverse transcriptase enzyme needed for viral replication. The promising results from this study build on earlier 24-week data and pave the way for pivotal Phase 3 trials. One of these upcoming studies will be open-label, similar to the Phase 2 trial, while the other will be blinded.

Baeten emphasized the varying preferences among patients, healthcare providers, and other stakeholders regarding treatment frequency. Their research indicates a nearly even split between those who would prefer a longer-acting pill and those who favor injections. This insight is crucial for developing treatment options that cater to diverse patient needs.

The Phase 2 study also revealed no significant differences in immune cell count changes between the Biktarvy group and the experimental group. This finding is particularly noteworthy given Merck’s earlier challenges with islatravir. In 2021, the company halted its development due to observed decreases in lymphocyte and CD4+ T cell counts in a different mid-stage study. Development resumed in 2022 with a lower dose of islatravir, which is being evaluated in combination studies, including the current trial. However, Merck ceased work on a once-monthly oral version for HIV prevention.

Lenacapavir has already received approval under the brand name Sunlenca for use alongside other antiretroviral drugs in treating individuals with multi-drug resistant HIV. Gilead has further plans to seek approval for a six-month injectable form of lenacapavir for HIV prevention, following positive outcomes from two Phase 3 studies. Regulatory submissions for this additional indication are anticipated by the end of the year.