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СпутникиРНSpaceXРоскосмосNASALong-acting cabotegravir plus rilpivirine (Cabenuva) achieved superior viral suppression vs daily oral antiretroviral therapy at 6months in treatment-experienced people with HIV and detectable viremia in the phase 3b CROWN trial.
The phase 3b CROWN trial (NCT06694805) met its primary endpoint.1,2 At 6 months, long-acting cabotegravir plus rilpivirine (Cabenuva; ViiV Healthcare) achieved superior rates of viral suppression vs standard-of-care oral antiretroviral therapy (ART) in adults and adolescents with HIV and detectable virus at study entry.1 Use of the regimen in people with viremia is investigational and has not been approved by regulatory authorities.1
The regimen is currently approved as Cabenuva in the US, and as Vocabria plus Rekambys in the EU and Japan, only for people who are virologically suppressed on a stable regimen.¹ Labeled patients must also have no history of treatment failure and no known or suspected resistance to either agent.1 ViiV Healthcare plans to share the CROWN data with health authorities for regulatory review.1
Data ResultsCROWN is an international, randomized, open-label superiority study enrolling approximately 326 adults and adolescents at 85 sites across eight countries.1 Participants either received cabotegravir plus rilpivirine long-acting (CAB + RPV LA) every two months, or six times a year, or continued oral ART.1,2 Eligible participants were aged 12 years or older, weighed at least 35 kg, and had screening HIV-1 RNA above 1000 copies/mL and below 100,000 copies/mL.2
Enrollment required a documented lapse in oral ART of at least 30 consecutive days, along with no evidence of resistance to integrase strand transfer inhibitors (INSTIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs).1,2 ViiV Healthcare has not yet released suppression rates, effect sizes, P values, or safety data from CROWN.1 Full results are planned for presentation at an upcoming scientific meeting.1
The findings build on the phase 3 LATITUDE trial (NCT03635788), in which 306 participants who first achieved suppression on oral ART were randomized to monthly CAB + RPV LA or continued oral therapy.3 Through 48 weeks, cumulative regimen failure was 22.8% with the long-acting regimen vs 41.2% with oral ART.3 Virologic failure occurred in 6.8% vs 28.2% of participants, respectively (difference, −21.4%; 98.4% CI, −33.5% to −9.3%).3
In LATITUDE, adverse event rates were similar between arms, and injection site reactions were the most common event in the long-acting group.3 Two long-acting arm participants with confirmed virologic failure developed new INSTI resistance-associated mutations.3 Cabenuva labeling carries warnings for hypersensitivity reactions, post-injection reactions, hepatotoxicity, and depressive disorders.3
"People living with HIV who experience challenges achieving or maintaining viral suppression with daily oral therapy continue to face significant barriers to optimizing care," Jean van Wyk, MBChB, MFPM, chief medical officer at ViiV Healthcare, said in a statement. "The CROWN study was designed to address this important evidence gap."1
CROWN met its primary endpoint, with long-acting cabotegravir plus rilpivirine given every two months outperforming oral ART for viral suppression at six months in viremic adults and adolescents.
CROWN is the first large randomized trial of direct initiation of the regimen in people with detectable virus, without a preceding oral suppression phase.
Use in people with viremia remains investigational; ViiV Healthcare plans to share the data with regulators and present full results at an upcoming scientific meeting.
Rilpivirine received FDA approval on May 20, 2011, as Edurant (Tibotec Therapeutics, now part of Johnson & Johnson), a once-daily oral NNRTI for treatment-naive adults with HIV.4 Cabotegravir was later paired with an extended-release injectable formulation of rilpivirine to form a two-drug complete regimen.5 ViiV received a complete response letter in February 2020 over chemistry, manufacturing, and controls before resubmitting.5
On January 21, 2021, the FDA approved Cabenuva as the first once-monthly, complete long-acting injectable regimen for virologically suppressed adults with HIV-1.6 The agency approved oral cabotegravir tablets (Vocabria) at the same time for an optional oral lead-in with rilpivirine.6 In February 2022, the FDA expanded the label to every-2-month dosing.
In March 2022, the FDA made the oral lead-in optional and extended the indication to virologically suppressed adolescents aged 12 years or older and weighing at least 35 kg.5 The adolescent approval drew on adult data supported by pharmacokinetic analyses showing similar drug exposure.5 CROWN now tests whether the regimen can move beyond suppressed patients to people starting injections while still viremic.
Contagion has followed the regimen through its initial FDA approval, its adolescent label expansion, and the launch of LATITUDE. Coverage has also included LATITUDE interim efficacy results and real-world data in people with adherence challenges.
If regulators accept the CROWN data, the indication could extend long-acting treatment to people unable to reach suppression on daily oral therapy.