By SPC News Staff

The FDA approved cabotegravir plus rilpivirine (CAB/RPV; Cabenuva, ViiV Healthcare/Janssen), the first long-acting injectable medication for HIV treatment.

CAB/RBV is dosed once monthly as an option to replace a patient’s current antiretroviral (ARV) regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable regimen, with no history of treatment failure, and with no known or suspected resistance to either cabotegravir or rilpivirine. Prior to initiating treatment of CAB/RPV injectable, patients should receive oral cabotegravir and rilpivirine for approximately one month to assess the tolerability of each therapy. 

CAB/RPV is administered as two intramuscular injections (cabotegravir and rilpivirine) in the buttocks during the same visit by a health care professional.

The approval of CAB/RPV is based on the pivotal phase 3 ATLAS (Antiretroviral Therapy as Long-Acting Suppression) and FLAIR (First Long-Acting Injectable Regimen) studies that included more than 1,100 patients from 16 countries. Prior to initiating treatment with CAB/RPV, oral dosing of cabotegravir and rilpivirine (lead-in) was administered for approximately one month. In these studies, CAB/RPV was as effective in maintaining viral suppression as continuing a daily oral three-drug regimen when injected intramuscularly in the buttocks once a month throughout the 48-week study period. 

ATLAS was a phase 3, open-label, active-controlled, multicenter, parallel-group, noninferiority study designed to assess the antiviral activity and safety of a two-drug regimen of long-acting injectable cabotegravir and rilpivirine dosed every four weeks, compared with continuation of current oral ARV of two nucleoside reverse transcriptase inhibitors plus an integrase inhibitor, non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor among virally suppressed individuals. The primary end point for ATLAS is the proportion of participants with plasma HIV-1 RNA of at least 50 copies/mL per the FDA Snapshot algorithm at week 48 (missing, switch or discontinuation = failure, intent-to-treat exposed [ITT-E] population). Subjects were required to be virally suppressed for six months or greater, on the first or second regimen, with no prior failure.

FLAIR is a phase 3, randomized, open-label, multicenter, parallel-group, noninferiority study designed to assess the antiviral activity and safety of a two-drug regimen of intramuscular, long-acting injectable cabotegravir and rilpivirine in virologically suppressed adults living with HIV, following 20 weeks of induction therapy with abacavir-dolutegravir-lamivudine (Triumeq, ViiV). The primary end point for FLAIR is the proportion of participants with plasma HIV-1 RNA of at least 50 copies/mL per the FDA Snapshot algorithm at week 48 (missing, switch or discontinuation = failure, ITT-E population).

In both studies, treatment was noninferior to the comparator regimens for HIV.

In both studies, the most common adverse reactions (grades 1-4) observed in at least 2% of clinical trial participants receiving CAB/RPV were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness and rash. Serious adverse events occurred in 4% (24/591) of patients taking CAB/RPV, and 3% (17/591) of adverse events led to withdrawal. For the full prescribing information, click here.

The injections were preferred by nine out of 10 patients over their previous daily oral therapy in these pivotal studies. Patient preference data were collected from clinical trial participants who received CAB/RPV. In a pooled exploratory analysis of this ITT-E population, 532 patients completed a single-item question at week 48 (59 patients did not); 88% (523/591) preferred CAB/RPV compared with 2% (9/591) who preferred their previous ARV treatment. The results were descriptive in nature and are not intended to imply clinical significance (N Engl J Med 2020;382[12]:1112-1123; N Engl J Med 2020;382[12]:1124-1135).

“Among the scientific community, we recognize the innovation behind Cabenuva is truly meaningful. Not only is it the first, complete long-acting regimen, which allows for a dramatic reduction in the frequency of dosing, but it also was preferred by most clinical trial participants when compared to their prior daily oral regimens,” said David Wohl, MD, a professor of medicine at the University of North Carolina Institute for Global Health and Infectious Diseases, in Chapel Hill, N.C. “The FDA approval of Cabenuva underscores the value of community-centric research.”

The complete regimen combines the integrase strand transfer inhibitor (INSTI) cabotegravir, developed by ViiV, with rilpivirine, an NNRTI, developed by Janssen. INSTIs inhibit HIV replication by preventing the viral DNA from integrating into T cells. This step is essential in the viral replication cycle and is responsible for establishing chronic infection. Rilpivirine is an NNRTI that works by interfering with the reverse transcriptase enzyme, which in turn stops the virus from multiplying.

To support the successful delivery of the once-monthly regimen to people living with HIV (PLHIV), ViiV sponsored the CUSTOMIZE trial, the first, pre-approval implementation science study to identify and evaluate approaches to integrate CAB/RPV into clinical practices in the United States. Interim findings presented at AIDS2020 demonstrated that at four months, the majority of clinical staff participants continued to perceive the implementation of CAB/RPV as highly acceptable, feasible and appropriate for PLHIV, and clinical staff had a substantial decrease in what they thought would be barriers to implementation of the injectable regimen (International AIDS Conference 2020; abstract LBPEE42).

“PRC provides legal, workforce and behavioral health services for those affected by HIV/AIDS in San Francisco. For years, many of our clients have struggled to manage their health while working to stabilize key aspects of their lives,” said Brett Andrews, the CEO of PRC. “Cabenuva will provide some people living with HIV greater freedom to pursue vocational, educational and other opportunities, like travel, without the need for daily oral medication management.”

The FDA also approved a New Drug Application for oral cabotegravir (Vocabria, ViiV) 30-mg tablets, which are given before the injectable medications. 

“Today’s FDA approval of Cabenuva represents a shift in the way HIV is treated, offering people living with HIV a completely new approach to care. Cabenuva reduces the treatment dosing days from 365 days to 12 days per year. At ViiV Healthcare, we are dedicated to ensuring no one living with HIV is left behind, and adding this first-of-its-kind regimen to our industry-leading portfolio of innovative medicines reinforces our mission,” said Lynn Baxter, the head of North America at ViiV.

ViiV said it will begin shipping CAB/RPV to U.S. wholesalers and specialty distributors in February.