Support for Gilead Drug’s Benefit Against Multidrug-Resistant HIV

NEW YORK (Reuters Health) – Gilead Sciences’ experimental subcutaneous HIV drug lenacapavir produces higher levels of viral suppression after 26 weeks among patients with multidrug-resistant disease when given in addition to other antiretrovirals, according to six-month results from the small CAPELLA trial.

Patients with multidrug-resistant HIV-1 infection “have limited treatment options. Lenacapavir is a first-in-class capsid inhibitor that showed substantial antiviral activity in a phase 1b study,” researchers note in the New England Journal of Medicine.

The phase-3 CAPELLA trial, which only had a brief 15-day window of placebo treatment, had two cohorts. The first was randomized and involved volunteers with at least 400 copies of the virus per milliliter. During the first 15 days as they continued on their failing therapy, 24 patients received oral lenacapavir and 12 got placebo. The lenacapavir recipients then received the subcutaneous version of the drug every six months plus optimized background therapy (OBT).

Placebo group members were switched to oral lenacapavir plus OBT 15 days into the study and then switched to the subcutaneous version.

The second cohort of 36 individuals, all with viral counts below 400, was not randomized. They received OBT immediately with 15 days of oral lenacapavir followed by subcutaneous injections of the drug on a six-month schedule.

For Cohort 1, during the first 15 days 88% of lenacapavir recipients saw a large deduction in HIV-1 RNA compared with only 17% in the placebo group (P<0.001).

At 26 weeks, 81% of the patients in Cohort 1 had fewer than 50 copies of HIV-1 RNA per ml of blood. The level was 83% in Cohort 2.

There were signs of lenacapavir resistance, which “warrants further investigation, given that some patients had viral load suppression while continuing to receive lenacapavir despite emerging resistance and minimal or no change in the optimized background therapy,” Dr. Sorana Segal-Maurer of the New York-Presbyterian Queens hospital in Flushing, New York, and colleagues report.

The 26-week findings from the study were originally released in July. In February, Gilead announced that 52-week results from the study showed that viral loads were kept below 50 copies per ml in 83% of 36 volunteers. There was only one adverse event leading to discontinuation of the study drug, the company said in a news release.

Injection-site reactions were seen in 63% of patients. Nausea and diarrhea occurred in 13% each.

SOURCE: The New England Journal of Medicine, online May 11, 2022.

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