The FDA yesterday approved a combination of two monthly injections for treatment of HIV in patients with stable disease exhibited by adequate viral suppression, with no prior history of treatment failure.
The injectable treatment, known as Cabenuva (cabotegravir and rilpivirine) was approved along with a tablet formulation of the two drugs which are to be taken for one month prior to starting the injections to make sure the medications are well tolerated before making the transition to the injectable form.
Cabenuva is a combination of 2 separate drugs, cabotegravir and rilpivirine, that are injected separately by a healthcare provider at the same appointment. In clinical trials, Cabenuva suppressed HIV to undetectable levels for 2 years. 90% of patients in a trial with Cabenuva states that they preferred having monthly injections over taking pills daily. A subsequent trial also found that Cabenuva was equally effective when given every 2 months as opposed to once a month. That said, the FDA approval only covers monthly use at this time, but it’s likely that application for bimonthly administration will be forthcoming.
“Currently, the standard of care for patients with HIV includes patients taking daily pills to adequately manage their condition. This approval will allow some patients the option of receiving once-monthly injections in lieu of a daily oral treatment regimen,” said John Farley, M.D., M.P.H., Director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research in a press release. “Having this treatment available for some patients provides an alternative for managing this chronic condition.”
The FDA approval comes as welcome news for patients who take 2-3 HIV medications daily (commonly known as ART, or antiretroviral therapy) and have difficulty with compliance, not to mention issues associated with perceived stigma of taking the daily medications themselves. Missing pills consistently is also a concern for patients and health care providers alike, since this increases the risk of developing resistance to the medications.
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We also know that persons with HIV may stop taking their medications for a variety of reasons including loss of insurance, being dropped from medication assistance programs, or issues related to mental health conditions, substance use, or incarceration. While the risk of developing drug resistance after missing medication is not particularly elevated, taking a long acting injectable or depot medication such as Cabenuva ensures that the medication persists in the blood stream even if some doses are missed. This low level of medication—while helpful in certain respects—could also allow the virus to develop resistance. Dealing with this possibility is an ongoing concern of researchers.
In one of the trials evaluating Cabenuva, 10 people developed resistance to the combination therapy; however, it’s still possible that a number of patients may also have developed resistance as a result of being prescribed similar medications in the recent past.
One issue is that the injectable drug will require more patients to visit their health care providers than in the past, potentially an issue during the pandemic. This could make adoption of this approach problematic over the next few years.
“Despite there being many great choices of once daily pill combinations to treat HIV now, there are many patients that will prefer this option of a once monthly injection,”said David Hirschwerk, MD, an Infectious Disease physician with Northwell Health. “Hopefully, for those patients who wish to adopt this, processes will be established to provide them the option.”
Adding to this, cost may also be a concern, as doses of the combination injectable therapy will run about $4,000 per month, in addition to $6,000 for the first dose based on data from ViiV Healthcare, reported by the New York Times. Affordability is certainly a chief concern when considering who can be placed on this treatment regimen. The treatment was well tolerated in the trials with pain at the injection site one of the more commonly reported concerns.
One concern about the recent FDA approval of Cabenuva is that it was only evaluated in trials in people who were healthy, and took daily oral HIV medications with undetectable viral loads, as opposed to those in whose disease was not particularly stable with higher viral loads. Of note, a trial to evaluate the long acting injectable approach with Cabenuva in those who are unable to comply with the strict daily regimens is currently in progress.
The approval of Cabenuva to treat HIV is one example of how a long acting injectable can impact the management of a chronic disease. “There are several chronic medical conditions, including rheumatologic illnesses for which regular injectables are a mainstay of treatment,” said Hirshwerk.