The U.S. Food and Drug Administration has approved Cabenuva, a groundbreaking long-acting HIV treatment that replaces daily pill regimens with monthly injections. This approval marks a significant shift in HIV treatment paradigms, offering patients an alternative that could improve adherence and quality of life.
Developed through a collaboration between ViiV Healthcare and Johnson & Johnson's Janssen pharmaceutical division, Cabenuva combines ViiV's integrase inhibitor cabotegravir with Janssen's non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (Edurant).
Overcoming Regulatory Hurdles
The approval comes after an unexpected setback in late 2019, when the FDA initially rejected the application due to deficiencies in chemistry, manufacturing, and controls (CMC) data. The clinical efficacy and safety data, however, had been deemed sufficient during the original review.
ViiV Healthcare, a joint venture majority-owned by GlaxoSmithKline with Pfizer and Shionogi as minority shareholders, worked to address the regulatory concerns over the past year before securing this landmark approval.
Clinical Evidence Supporting Approval
The FDA's decision was based on the pivotal Phase III ATLAS studies, which enrolled more than 1,100 patients across 16 countries. These trials demonstrated that Cabenuva, administered as a monthly intramuscular injection in the buttocks, was as effective in maintaining viral suppression as standard three-drug daily oral regimens throughout the 48-week study period.
Before initiating the injectable treatment, patients undergo approximately one month of oral dosing with cabotegravir and rilpivirine to assess tolerability of the medications.
Patient Preference and Adherence Benefits
A significant finding from the clinical program was the strong patient preference for the injectable regimen. In a survey conducted alongside one of the pivotal trials, 88% of the 532 respondents indicated they preferred Cabenuva over their previous daily oral HIV treatment. Only 2% preferred their prior oral therapy, while 59 patients opted not to answer the questionnaire.
Dr. Kimberly Smith, Head of Research & Development at ViiV Healthcare, stated, "This approval marks a significant advancement in how we approach HIV treatment. The ability to replace daily pills with monthly injections will be transformative for many patients, potentially improving adherence while reducing the daily reminder of living with HIV."
Safety Profile
The most common adverse reactions reported in at least 2% of clinical trial participants receiving Cabenuva included injection site reactions, fever, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash.
Serious adverse events occurred in 4% (24/591) of patients taking Cabenuva, with 3% (17/591) of adverse events leading to withdrawal from the studies.
Pricing Structure
ViiV Healthcare has announced a tiered pricing approach for Cabenuva. Patients will receive a month-long course of oral medication at no charge, followed by an initial higher-dose injection priced at $5,940. Subsequent monthly maintenance doses will cost $3,940 each.
Implications for HIV Care
This approval represents the first major shift away from daily oral therapy since the introduction of combination antiretroviral treatment transformed HIV from a fatal diagnosis to a manageable chronic condition.
"The burden of daily pill-taking is significant for many people living with HIV," explained Dr. David Wohl, Professor of Medicine at the University of North Carolina School of Medicine, who was involved in the clinical trials. "Having a monthly option could help address issues of treatment fatigue, privacy concerns, and adherence challenges that some patients face."
Future Developments
While the current approval is for monthly administration, clinical trials have suggested the potential for extending the dosing interval to every eight weeks. ViiV and Janssen initially opted to file for the four-week regimen but may pursue the longer interval in future submissions.
The injectable regimen is also under regulatory review in Europe, where a decision is anticipated in the coming months.
For patients and providers, this approval offers a new paradigm in HIV care, though it will require adjustments to healthcare delivery systems as patients will need to visit clinics monthly for injections rather than the typical once or twice yearly provider visits that many stable HIV patients currently maintain.
