Kiniksa Pharmaceuticals reported positive data from RHAPSODY, a pivotal Phase 3 trial of rilonacept, a weekly, subcutaneously-injected, recombinant fusion protein, in recurrent pericarditis. RHAPSODY met its prespecified primary and all major secondary efficacy endpoints. Based on this data, Kiniksa expects to submit a Supplemental Biologics License Application (sBLA) later this year.
RHAPSODY was a global, randomized withdrawal design, pivotal trial. The trial’s primary analysis population included 61 actively symptomatic recurrent pericarditis patients who were failing standard of care treatment, including nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, or corticosteroids, initiated rilonacept treatment during a run-in period, discontinued background medications, and achieved and maintained clinical response (11-point pain Numerical Rating Scale (NRS) ≤ 2.0 and C-reactive protein (CRP) ≤ 0.5 mg/dL) on rilonacept monotherapy. Clinical responders were randomized 1:1 to receive continued weekly rilonacept (n=30) or placebo (n=31) in a blinded manner in the randomized withdrawal period.
The primary efficacy endpoint of time-to-first adjudicated pericarditis recurrence in the randomized withdrawal period was highly statistically significant. The median time to pericarditis recurrence for rilonacept recipients in the randomized withdrawal period could not be estimated due to the low number of recurrences in the rilonacept treatment arm. The median time-to-recurrence for placebo recipients was 8.6 weeks. Rilonacept recipients experienced a 96% reduction in risk of recurrent pericarditis events.
All major secondary efficacy endpoints in the randomized withdrawal period were also highly statistically significant over placebo, including maintenance of clinical response at Week 16 and up to Week 24, and the proportion of rilonacept recipients with absent or minimal pericarditis symptoms at Week 16 of the randomized withdrawal period and up to Week 24. Rilonacept was well-tolerated.
Rilonacept was discovered and developed by Regeneron Pharmaceuticals and is approved by the FDA under the brand name ARCALYST for the treatment of CAPS. Kiniksa licensed rilonacept from Regeneron in 2017 for IL-1α and IL-1β mediated diseases, including recurrent pericarditis. The FDA granted Breakthrough Therapy designation to rilonacept for recurrent pericarditis in 2019. Based on the Phase 3 RHAPSODY data, the Biologic License Application (BLA) for CAPS will transfer to Kiniksa, and the company plans to submit an sBLA with the FDA in recurrent pericarditis later this year. Upon receipt of FDA approval for rilonacept in recurrent pericarditis, Kiniksa wil assume the sales and distribution of rilonacept for the approved indications in the United States and will evenly split profits on sales with Regeneron.
Rilonacept is a weekly, subcutaneously-injected, recombinant fusion protein that blocks IL-1α and IL-1β signaling.
About Recurrent Pericarditis
Recurrent pericarditis is a painful and debilitating autoinflammatory cardiovascular disease that typically presents with chest pain and is often associated with changes in electrical conduction and sometimes buildup of fluid around the heart, called pericardial effusion. Patients with pericarditis are deemed recurrent if they have an additional episode after a symptom-free period of 4-6 weeks, and chronic if symptoms from any one episode last longer than three months. Recurrent pericarditis symptoms impair qualify of life, limit physical activities, and lead to frequent emergency department visits and hospitalizations. There are currently no FDA-approved treatments for recurrent pericarditis.