FDA Approves First Long-Acting Injectable to Prevent HIV Infection

The first long-acting injectable for HIV prevention has now been approved for use, the FDA announced on Monday.

Long-acting injectable cabotegravir (CAB-LA, branded as Apretude) is administered as a monthly injection for the first 2 months, then every 2 months afterwards. It is the first long-acting injectable for pre-exposure prophylaxis (PrEP). The drug is approved for adults and adolescents weighing at least 77 lb.

This is the first option for HIV PrEP that does not involve taking a daily pill, noted FDA's Director of the Division of Antivirals in the FDA's Center for Drug Evaluation and Research, Debra Birnkrant, MD.

She added that this will help "high-risk individuals and certain groups where adherence to daily medication has been a major challenge or not a realistic option."

AVAC: Global Advocacy for HIV Prevention also applauded the news.

"With as few as six shots per year, this highly effective form of injectable PrEP can help bend the curve of the HIV epidemic – but only if its approval is accompanied by strategic, effective and equitable rollout that transforms the growing list of HIV prevention options into real and accessible choices for the people who need prevention most," said AVAC Executive Director, Mitchell Warren, in a statement.

Of the 1.2 million individuals in the U.S. who are recommended for PrEP, only 25% are actually prescribed it, according to the FDA.

"The approval of CAB-LA is a vital shot in the arm for HIV prevention," Warren noted.

CAB-LA's approval was based on two randomized trials, one in cisgender men and transgender women, and one in cisgender women. Participants in the CAB-LA arm took oral cabotegravir for 5 weeks, then had two injections of cabotegravir a month apart, and one injection every 2 months afterwards, plus a daily placebo.

Participants in the emtricitabine/tenofovir (Truvada, together dubbed TDF/FTC) arm took those oral drugs and a placebo daily for up to 5 weeks, then had two injections of placebo a month apart and every 2 months afterwards, plus daily TDF/FTC.

In the trial of 4,566 cisgender men and transgender women, risk of HIV infection was 69% lower in the CAB-LA arm versus the TDF/FTC arm, the agency said. The disparity was even greater among 3,224 cisgender women, where the risk was 90% lower in the CAB-LA arm versus TDF/FTC arm.

In addition to injection site reactions, headache, pyrexia, fatigue, back pain, myalgia, and rash were more common in the CAB-LA arm versus the TDF/FTC arm. The drug also carries warnings about hypersensitivity reactions, hepatotoxicity, and depressive episodes.

FDA added that patients can either start their treatment with CAB-LA or take oral cabotegravir (Vocabria) for a month to see if they can tolerate the drug.

CAB-LA has a boxed warning that states it should only be used once a negative HIV diagnosis is confirmed, as drug-resistant variants have emerged in those who contract HIV while using the drug. If a patient is infected with HIV while on the drug, they should be transitioned to an HIV treatment regimen, the agency added.

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