Janssen Announces U.S. FDA Approval of CABENUVA (rilpivirine and cabotegravir), the First Long-Acting Regimen for the Treatment of HIV

TITUSVILLE, N.J., Jan. 21, 2021 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the U.S. Food and Drug Administration (FDA) has approved CABENUVA (consisting of Janssen's rilpivirine and ViiV Healthcare's cabotegravir), the first and only once-monthly, long-acting regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults. The novel regimen was co-developed as part of a collaboration with ViiV Healthcare and builds on Janssen's 25-year commitment to make HIV history. In the U.S., ViiV Healthcare is the marketing authorization holder for CABENUVA.

CABENUVA is indicated as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen, with no history of treatment failure, and with no known or suspected resistance to either cabotegravir or rilpivirine. Prior to initiating treatment with CABENUVA, oral cabotegravir (VOCABRIA) and oral rilpivirine (EDURANT®) should be administered for approximately one month to assess the tolerability of each therapy.

CABENUVA, a co-packaged kit with two injectable medicines, offers people living with HIV a new approach for maintaining viral suppression.

"With the approval of CABENUVA, we're proud to bring a new treatment option to people living with HIV that removes the burden of taking a daily pill," said Paul Stoffels, M.D., Vice Chairman of the Executive Committee and Chief Scientific Officer, Johnson & Johnson. "While much more remains to be done to make HIV history, today's milestone reminds us how far medical innovation has come since the first reported cases of the virus almost 40 years ago."

The approval of CABENUVA 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, including the U.S. The studies demonstrated that CABENUVA was as effective as continuing a daily, oral, three-drug regimen in maintaining viral suppression throughout the 48-week study period.

In the ATLAS study, CABENUVA met the primary endpoint for noninferiority (the proportion of participants with plasma HIV-1 RNA ≥50 copies per milliliter [c/mL] at Week 48), with a comparable number of patients receiving either CABENUVA or their daily current antiretroviral regimen (CAR) having an HIV-1 RNA level ≥50 c/mL. Two percent of patients receiving the long-acting injectable and 1% of patients receiving CAR had an HIV-1 RNA level ≥50 c/mL at Week 48 (Treatment Difference 0.7%; 95% CI: -1.2%, 2.5%).

In the FLAIR study, at Week 48, a comparable number of patients receiving either CABENUVA or daily oral dolutegravir/abacavir/lamivudine therapy had an HIV-1 RNA count ≥50 c/mL, meeting noninferiority criteria. Two percent of patients in both treatment arms had an HIV-1 RNA count ≥50 c/mL at Week 48 (Treatment Difference -0.4%; 95% CI: -2.8%, 2.1%).

Adverse reactions of at least Grade 2 severity in patients who were receiving CABENUVA or CAR were, respectively: injection site reactions (37%, 0), pyrexia (2%, 0), fatigue (1%, <1%), headache (<1%, <1%), musculoskeletal pain (1%, 0), nausea (<1%, 0), sleep disorders (<1%, 0), dizziness (<1%, 0) and rash (<1%, 0).

Results from these trials were presented at the 2019 Conference on Retroviruses and Opportunistic Infections (CROI).

"This is an exciting new option for patients and providers, as it provides an alternative strategy for effective HIV treatment," said Susan Swindells, MBBS, Professor, Department of Internal Medicine, University of Nebraska Medical Center. "CABENUVA once-monthly injections showed comparable efficacy to daily oral antiretroviral treatment in maintaining viral suppression – a first in the treatment paradigm."

"For more than 25 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."

The once-monthly rilpivirine and cabotegravir injectable treatment was approved by Health Canada on March 20, 2020, and 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.

About CABENUVA (rilpivirine and cabotegravir)

CABENUVA is approved as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine. CABENUVA is administered by a healthcare provider once-monthly as two individual intramuscular injections in the buttocks.

The complete regimen combines rilpivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) developed by Janssen Sciences Ireland UC, with the integrase strand transfer inhibitor (INSTI) cabotegravir, developed by ViiV Healthcare.

INSTIs, like cabotegravir, inhibit HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection.

Rilpivirine is an NNRTI that works by interfering with an enzyme called reverse transcriptase, which in turn stops the virus from multiplying.

About EDURANT® (rilpivirine)

EDURANT® (rilpivirine), in combination with other antiretroviral agents, is a non-nucleoside reverse transcriptase inhibitor (NNRTI) indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-naïve patients 12 years of age and older and weighing at least 35 kg with HIV-1 RNA less than or equal to 100,000 copies/mL at the start of therapy.

Jan 22, 2021

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