FDA Approves a Complete Long-Actimng Injectable Regimen for HIV Treatment
by Hank Trout
On January 21, 2021, The U.S. Food and Drug Administration (FDA) approved Cabenuva, a breakthrough injectable drug combination of cabotegravir (an integrase strand transfer inhibitor, or INSTI, developed by ViiV Healthcare) and rilpivirine (a non-nucleoside reverse transcriptase inhibitor, or NNRTI, developed by Janssen Sciences Ireland UC) as a complete regimen for the treatment of HIV-1 infection in adults who are virologically suppressed (HIV1 RNA less than 50 copies per mL). This is the first FDA-approved complete injectable regimen for HIV-infected adults. Cabenuva is given every four weeks by medical providers in the form of two injections. It is the latest option for treating HIV.
To start on the injectable medication, the presence of virus in a patient’s blood must be nearly zero (virally suppressed). The Centers for Disease Control and Prevention estimated in 2018 that about sixty-five percent of people living with HIV will qualify for Cabenuva.
The FDA’s approval of Cabenuva was 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 sixteen countries, including the U.S. The studies demonstrated that Cabenuva was as effective as continuing a daily, oral, three-drug regimen in maintaining viral suppression. INSTIs like cabotegravir inhibit HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T cells). The studies also found that nine out of ten participants in the study preferred the once monthly injectable treatment to their previous daily oral therapy.
Rilpivirine is an NNRTI that works by interfering with an enzyme called reverse transcriptase, which in turn stops the virus from multiplying. The FDA also approved Vocabria (cabotegravir, tablet formulation), which should be taken in combination with oral rilpivirine (Edurant) for one month prior to starting treatment with Cabenuva to ensure the medications are well-tolerated before switching to the extended-release injectable formulation.
Cabenuva was previously approved by Health Canada on March 20, 2020; the European Commission approved a once-monthly and once every two-month version of the injectable treatment on December 21, 2020. Regulatory reviews continue in Australia and Switzerland, and several additional submissions are planned throughout 2021.
Sixty-two-year-old Suzi, one of the patients in the clinical trial for Cabenuva, was diagnosed with HIV in 2006 at the age of forty-eight and had been on a daily oral regimen for years. “I didn’t like taking pills every day because it reminded me of my HIV status so I was interested in trying something new,” she told A&U. “[M]y doctor…told me about the ATLAS study. I qualified for the clinical trial and when I got my first injections, I cried tears of joy. I was so grateful to hand over my daily pills.” She has been taking Cabenuva since then.
“I’m doing very well,” Suzi continued. “It is a wonderful fit for me and my lifestyle. The injections are quick and easy and then I just go about my business until the next time, and I find that I barely think about having HIV anymore. I do get soreness after the injections; moving around in the days after the injections helps. I also get a bit tired. All in all, I quickly adapted to it and the medicine is a great choice for me.”
Of course, no HIV treatment comes without side effects. The most common adverse reactions with Cabenuva were injection site reactions, fever, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness and rash. Cabenuva should not be used if there is a known previous hypersensitivity reaction to cabotegravir or rilpivirine, or in patients who are not virally suppressed.
The new injectable comes with a high cost: The wholesale acquisition cost of the monthly medications is $3,960, and the price of an initiation dose is $5,940. Officials at Janssen and ViiV said they believe the drugs will be covered by private insurance, Medicare and Medicaid, and ADAP, as many other HIV drugs are.
“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.”
“For more than twenty-five years, we have been committed to changing the course of the HIV epidemic through the pursuit of innovative treatments and effective prevention,” said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, Johnson & Johnson. “This new treatment option for people living with HIV brings us one step closer toward alleviating this global health threat.”
A January 22, 2021 article in The Washington Post quoted Steven Harris, a 41-year-old Pittsburgh man who has been receiving the injectable drugs for two years as part of a clinical trial, said: “What I discovered after I started… [is] that there’s actually a really large benefit that I hadn’t expected. Until I was really away from the pills, I didn’t really realize the psychic toll it was taking on me.” Now, with Cabenuva, Harris said, he is more able to “live my daily, normal life and just forget about my HIV.”
Monica Gandhi, an HIV researcher at the University of California at San Francisco and medical director of San Francisco General Hospital’s HIV clinic, Ward 86, told the Post that the development represents “an incredible and exciting breakthrough, a day we’ve been waiting for.”
Hank Trout, Senior Editor, edited Drummer, Malebox, and Folsom magazines in the early 1980s. A long-term survivor of HIV/AIDS (diagnosed in 1989), he is a forty-year resident of San Francisco, where he lives with his husband Rick.