One month after the Food and Drug Administration (FDA) approval of monthly rilpivirine/cabotegravir (Cabenuva) for HIV, Janssen has submitted evidence of efficacy with dosing every 2 months.
One month after receiving FDA approval for Cabenuva as a monthly treatment of HIV-1, Janssen Pharmaceutical Companies of Johnson & Johnson has filed a supplemental New Drug Application (sNDA) with evidence that efficacy is maintained with every 2 month dosing.
The combination of the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (Janssen) and the integrase strand transfer inhibitor (INSTI) cabotegravir (ViiV Healthcare) was approved in January as a complete treatment of HIV-1 infection in monthly injections that can replace a previously stable antiretroviral treatment (ART) regimen for adults who are virologically suppressed (HIV-1 RNA less than 50 copies/ml) and without history of treatment failure or resistance to either component of the product.
"First, with the introduction in the US of Cabenuva as a once-monthly injection, and now as we pursue approval for its use every two months, we're proud to be evolving the treatment options available for those affected by HIV," stated Brian Woodfall, MD, global head, Development, Infectious Diseases, Janssen Biopharma, in the announcement issued by Janssen.
The sNDA submitted to the FDA in February to expand the approved administration to every 2 months is based on data from the phase 3b ATLAS-2M (Antiretroviral Therapy as Long-Acting Suppression) study comparing efficacy to that with monthly injections over a 48-week study period.
Non-inferiority was established by the comparable proportion of participants who exceededvirologic suppression threshold at week 48, using the FDA Snapshot algorithm (Intent-to-Treat Exposed [ITT-E] population): 1.7% (9/522) in the every-two-month group compared with 1.0% (5/523) in the once-monthly group (adjusted difference: 0.8%; 95% CI -0.6-2.2).
The key secondary endpoint was met, with similarity of virologic suppression rates between groups: 94.3% (492/522) and 93.5% (489/523) in the every two-months and monthly groups, respectively.
According to the announcement, treatment was well-tolerated across both study arms. Rates of serious adverse event were 5.2% (27/522), and withdrawals due to adverse events were 2.3% (12/522) in the every-two-months group. These were similar in the once-monthly group, with 3.6% (19/523) serious adverse event and 2.5% (12/523) withdrawals due to adverse events.
The most common adverse reactions (incidence ≥2%, all grades) were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash.
The approved labeling advises oral dosing of the combination for approximately 1 month to assess tolerability prior to initiating the injectable regimen (ie, 30mg cabotegravir and 25mg rilpivirine daily).It is recommended that the injections (in separate gluteal intramuscular sites) are initiated on the last day of oral lead-in; with caution that a delay of longer than 1 month risks developing viral resistance.The approved initial dosage, in the "starting kit," is a single 600mg injection of cabotegravir and a single 900mg injection of rilpivirine. Maintenance dosing is 400 and 600mg, respectively.
On the occasion of the FDA approval of the once-monthly injection in January, Johnson & Johnson Vice Chairman of the Executive Committee and Chief Scientific Officer Paul Stoffels, MD, commented, "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."