The FDA approved lenacapavir, which is the first approval of a drug in a new class of antiretrovirals for the treatment of HIV-1 called capsid inhibitors.
Lenacapavir (Sunlenca; Gilead Sciences) is a first-in-class capsid inhibitor approved by the FDA for the treatment of adult patients with HIV type 1 (HIV-1) whose HIV infections cannot be successfully treated with other available treatments due to resistance, intolerance, or safety concerns. By blocking the HIV-1 virus’ capsid, or protein shell, capsid inhibitors such as lenacapavir work differently from other currently approved antiretrovirals as they interfere with multiple essential parts of the viral lifecycle.
Additionally, lenacapavir allows a greater level of convenience for patients as it is administered as a subcutaneous injection once every 6 months following the starting dose, which is given as a combination of subcutaneous injections and oral tablets. After the starting dose, the maintenance injections administered every 6 months can be given in combination with other antiretrovirals.
In a multicenter clinical trial, lenacapavir’s safety and efficacy were established based on the results of treating 72 patients with HIV-1 whose HIV infections were resistant to multiple classes of HIV medications and continue to have high levels of virus in their blood. Patients were placed into 1 of 2 study arms, with 1 arm randomized to receive either lenacapavir or placebo in a double-blind fashion, and the other to receive open-label lenacapavir. During the trial, efficacy was primarily measured based on the proportion of patients in the randomized cohort who achieved a certain level of reduction of the virus during the first 14 days following administration when compared with their baseline.
In the randomized group, 87.5% of patients who received lenacapavir achieved a viral decrease while 16.7% of patients achieved a viral decrease in the placebo group. Following 26 weeks of receiving lenacapavir plus other antiretroviral drugs as a maintenance combination therapy, 81% of participants in the randomized group achieved HIV RNA suppression, with levels of HIV low enough to be considered undetectable. Following 52 weeks of this maintenance combination therapy, 83% of participants continued to demonstrate HIV RNA suppression.
During the trial, the investigators observed nausea and injection site reactions, such as swelling, pain, or redness, as the most common adverse events (AEs) that occurred with lenacapavir treatment. However, some injection site reactions that were observed could be described as nodules or indurations and were found to be persistent in some patients. The investigators noted that additional warnings and precautions include the risk of developing immune reconstitution syndrome, which occurs when the immune system overreacts to HIV treatment.
Additionally of note, if treatment with lenacapavir ceases due to the occurrence of AEs, residual amounts of lenacapavir can remain in the body for a year or more and can potentially cause drug interactions, even at low levels. Further, if a patient misses doses of lenacapavir or fails to maintain a fully suppressive HIV treatment regimen after stopping lenacapavir, this could potentially lead to an increased risk of developing viral resistance.
If a patient takes certain drugs that cause reduced levels of lenacapavir, they should not be given lenacapavir. In such a case, patients who are given lenacapavir may lose virologic response and develop viral resistance.
“Today’s approval ushers in a new class of antiretroviral drugs that may help patients with HIV who have run out of treatment options,” said Debra Birnkrant, MD, director of the Division of Antivirals in the FDA’s Center for Drug Evaluation and Research, in a press release. “The availability of new classes of antiretroviral medications may possibly help these patients live longer, healthier lives.”
FDA. FDA Approves New HIV Drug for Adults with Limited Treatment Options. FDA website. December 22, 2022. Accessed December 22, 2022. https://content.govdelivery.com/accounts/USFDA/bulletins/33ee4a6.