FDA Issues Complete Response Letter to Investigational Long-Acting HIV Regimen

Officials with the FDA have issued a complete response letter (CRL) in response to ViiV Healthcare’s New Drug Application (NDA) for the 2-drug long-acting (LA) injectable HIV treatment regimen, according to a press release.¹

The NDA is seeking approval for ViiV Healthcare’s cabotegravir and Janssen’s rilpivirine for the treatment of HIV in adults. Cabotegravir is an integrase strand transfer inhibitor and rilpvirine is a non-nucleoside reverse transcriptase inhibitor.¹

According to ViiV Healthcare and Janssen, the reasons given in the CRL relate to Chemistry Manufacturing and Controls (CMC), and there have been no reported safety issues related to CMC and no change to the safety profile of the products.¹

The NDA is backed by data from 2 clinical study programs: Antiretroviral Therapy as Long-Acting Suppression (ATLAS) and First Long-Acting Injectable Regimen (FLAIR). Combined, the studies included more than 1100 patients and showed that the combination regimen, injected monthly, was non-inferior to standard-of-care, daily, oral, 3-drug regimen in maintaining viral suppression through 48 weeks.²

The ATLAS study assessed the antiviral activity and safety of the 2-drug LA injectable regimen dosed every 4 weeks compared with continuation of current oral antiretroviral therapy (ART) of 2 nuceloside reverse transcriptase inhibitors, non-nuceleoside reverse transcriptase inhibitor, or protease inhibitor, among virally suppressed individuals. The primary endpoint was the proportions of participants with plasma HIV-RNA ≥50 copies per milliliter (c/mL) using the FDA Snapshot algorithm at week 48.²

For the FLAIR study, the 2-drug LA regimen was evaluated virologically suppressed adults with HIV following 20 weeks of induction therapy with abacavir, dolutegravir, and lamivudine tablets (Triumeq). The primary endpoint was the proportion of participants with plasma HIV-1 RNA ≥50 c/mL per the FDA Snapshot algorithm at week 48.²

If approved, cabotegravir and rilpivirine would be the first LA, injectable treatment regimen for HIV, according to ViiV. Rilpivirine is currently approved in oral formulation for the treatment of HIV-1 in combination with other ART.²

“We believe the once-monthly, long-acting regimen represents an important therapeutic advance for those living with HIV,” Brian Woodfall, MD, Global Head, Development, Infectious Diseases, Janssen Biopharma, Inc, said in a statement.³ “We will continue to collaborate with our partners and the FDA to fully understand the requirements needed to support US approval as we continue in our efforts to change the course of the HIV epidemic.”

References:

• ViiV Healthcare receives complete response letter from US FDA for use of investigational cabotegravir and rilpivirine long-acting regimen in the treatment of HIV [news release]. ViiV Healthcare’s website. https://viivhealthcare.com/en-gb/media/press-releases/2019/december/complete-response-letter-from-us-fda/. Accessed January 3, 2020.

• ViiV Healthcare Submits New Drug Application to US FDA for the First Monthly, Injectable, Two-Drug Regimen of Cabotegravir and Rilpivirine for the Treatment of HIV [news release]. ViiV Healthcare’s website. https://viivhealthcare.com/en-gb/media/press-releases/2019/april/viiv-healthcare-submits-new-drug-application-to-us-fda-for-the-first-monthly-injectable-two-drug-regimen-of-cabotegravir-and-rilpivirine-for-treatment-of-hiv/. Accessed January 3, 2020.

• Complete Response Letter Issued from US FDA for Investigational Long-Acting HIV Regimen [news release]. Janssen’s website. https://www.janssen.com/complete-response-letter-issued-us-fda-investigational-long-acting-hiv-regimen. Accessed January 3, 2020.