ViiV Healthcare Will Not Continue Trials of Subcutaneous Cabenuva | AIDS 2024

A subcutaneous version of Cabenuva (cabotegravir and rilpivirine) has similar efficacy to the intramuscular injection in maintaining suppression of HIV, but many patients in a substudy of the phase 3 FLAIR trial found the self-injectable to be painful and led to nodules and reddening of the skin, according to results presented during a session at the International AIDS Conference in Munich, Germany.

“The sub q injections led to a higher incidence and longer duration of ISR [injection site reactions], resulting in lower acceptability of and satisfaction with sub q injections. As a result, further development of this treatment regimen for sub q self-administration will not be pursued,” said Ronald D’Amico, associate medical director at ViiV Healthcare, who presented the study during a session at the AIDS Conference. “ViiV Healthcare, however, remains committed to evaluating alternative drugs for the potential for self-administration.”

Developed by ViiV Healthcare, Cabenuva is a long-acting therapy for patients 12 years and older with HIV to maintain virus suppression. It is approved by the FDA to be given as an intramuscular injection and can be given monthly or every two months.

D’Amico noted in his presentation that previous data in healthy volunteers who received Cabenuva indicated they were supportive of further evaluations of a subcutaneous version.

The phase 3 FLAIR study demonstrated non inferior efficacy of switching from daily oral therapy to long-acting Cabenuva. At week 48, 91% of participants preferred a long-acting therapy. These data were published in The New England Journal of Medicine in March 2020. Updated 96 week results were published in April 2021 in The Lancet HIV.

During his presentation, D’Amico discussed results from an optional substudy of the FLAIR trial. Participants were eligible to enroll into the substudy after receiving a minimum of 12 months of long-acting therapy with no history of suspected virologic failure and who had undetectable HIV-1 below 50 copies per milliliter (mL).

In the substudy, 93 patients received intramuscular injections during screening, three subcutaneous injections at day 1, week 4 and week 8. They returned to intramuscular injections at week 12 and week 16. Researchers measured pharmacokinetics, safety, tolerability, efficacy, and patient reported outcomes.

Although this was not a formal bioequivalence study, D’Amico said plasma exposures were comparable for intramuscular and subcutaneous administration, with a 90% confidence interval and 90% maintained. No participant experienced a suspected or confirmed virologic failure.

But at week 9, 59% of 85 participants preferred the intramuscular injections, most commonly citing less injection site swelling and fewer nodules, and 34% of 85 participants preferred subcutaneous injection, most commonly citing convenience.

The most common injection site reactions from the subcutaneous injection were pain (48%), nodules (34%) and redness (26%). Five participants withdrew because of injection site reactions from the subcutaneous version.

There were no non-injection site reactions that led to withdrawal.