Bictegravir-Lenacapavir Combo Pill Earns FDA Approval in Suppressed HIV

The FDA approved the combination of bictegravir and lenacapavir (Bixlenvo) for adults with virologically suppressed HIV-1 infection, Gilead Sciences announced Thursday.

The once-daily single tablet contains 75 mg of the integrase strand transfer inhibitor (INSTI) bictegravir and 50 mg of the capsid inhibitor lenacapavir. The treatment is indicated in adults with HIV-1 RNA levels less than 50 copies per mL who are switching from a stable antiretroviral regimen and have no resistance to the two drugs.

“The approval is a significant advancement in HIV treatment, especially for individuals unable to benefit from guideline-recommended single-tablet regimens due to challenges like pre-existing resistance or tolerability,” said Chloe Orkin, MBBCH, MSc, of Queen Mary University of London, in a Gilead Sciences statement. “It expands tailored, simplified dosing to people whose needs were not fully met by existing single-tablet therapies.”

The FDA based its decision on two phase III clinical trials, ARTISTRY-1 and ARTISTRY-2.

ARTISTRY-1 included 557 people with virologically suppressed HIV on complex oral regimens. Among those randomized to switch to the single-tablet bictegravir-lenacapavir combination, 0.8% had HIV-1 RNA levels of 50 copies or more per mL after 48 weeks of treatment compared with 1.1% of those who remained on their complex regimen. There was no detected resistance to the two drugs in the single tablet after treatment. Adverse events were comparable between the two study arms, including serious adverse events.

In ARTISTRY-2, the bictegravir-lenacapavir combination pill was noninferior to combination bictegravir, emtricitabine, and tenofovir alafenamide (Biktarvy). After 48 weeks, 1.3% of those who switched to bictegravir-lenacapavir had HIV-1 RNA of 50 or more compared with 1.0% who remained on the three-drug pill. Drug-related adverse event rates were similar between the two treatment groups, with no serious drug-related adverse events.

Under the approved indication, patients begin a 2-day initiation regimen of one tablet of bictegravir-lenacapavir plus two tablets of 300-mg lenacapavir (Sunlenca) followed by a maintenance regimen of one tablet of bictegravir-lenacapavir once daily. Tablets may be taken with or without food. The drug’s label warns that bictegravir-lenacapavir shouldn’t be given with dofetilide or strong CYP3A inducers, nor should it be given with other antiretroviral medications to treat HIV-1 infection.

The most common adverse reactions were headache, nausea, and diarrhea.

Oral lenacapavir is being studied in other therapeutic combinations for suppressed HIV. Weekly oral lenacapavir with islatravir matched daily oral standard-of-care regimens in patients with virologically suppressed HIV, according to two phase III trials presented at the International AIDS Conference in Rio de Janeiro this year.