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Abstract Number: 1454

RHAPSODY: Rilonacept, an IL-1α and IL-1β Trap, Resolves Pericarditis Episodes and Reduces Risk of Recurrence in a Phase 3 Trial of Patients with Recurrent Pericarditis

Allan Klein1, Massimo Imazio2, Paul Cremer1, Antonio Brucato3, Antonio Abbate4, Fang Fang5, Antonella Insalaco6, Martin LeWinter7, Basil S. Lewis8, David Lin9, Sushil A. Luis10, Stephen J. Nicholls11, Arian Pano5, Alistair Wheeler12, Liangxing Zou5 and John F Paolini5, 1Department of Cardiovascular Imaging, Center for the Diagnosis and Treatment of Pericardial Diseases, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, 2University Cardiology, Cardiovascular and Thoracic Department, AOU Città della Salute e della Scienza di Torino, Torino, Italy, 3Department of Biomedical and Clinical Science, University of Milano, Fatebenefratelli Hospital, Milan, Italy, 4VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, 5Kiniksa Pharmaceuticals Corp., Lexington, MA, 6Department of Pediatric Medicine, Division of Rheumatology, Bambino Gesù Children's Hospital, Rome, Italy, 7Cardiology Unit, The University of Vermont Medical Center, The University of Vermont, Burlington, VT, 8Cardiovascular Clinical Research Institute, Lady Davis Carmel Medical Center, Haifa, Israel, 9Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis, MN, 10Division of Cardiovascular Ultrasound, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, NY, 11MonashHeart, Department of Cardiology, Monash University, Clayton, Australia, 12Kiniksa Pharmaceuticals, Ltd., Hamilton, Bermuda

Meeting: ACR Convergence 2021

Keywords: , ,

Session Information

Date: Monday, November 8, 2021

Title: Abstracts: Miscellaneous Rheumatic & Inflammatory Diseases: New Insights into Therapies & Mechanisms of Disease (1452–1457)

Session Type: Abstract Session

Session Time: 4:00PM-4:15PM

Background/Purpose: Recurrent pericarditis (RP) is an autoinflammatory disease with no FDA-approved therapies. RHAPSODY, a global Phase 3 study, evaluated rilonacept, a once-weekly IL-1α/IL-1β trap, in RP. RHAPSODY data helped support FDA approval of the first therapy for RP.

Methods: RHAPSODY was a randomized withdrawal (RW) trial: 86 patients (pts) with acute symptomatic RP, failing standard therapy (NSAIDs, colchicine, and/or corticosteroids [CS]), enrolled in a 12-week single-blind run-in (RI) period: rilonacept (320 mg SC load, 160 mg SC weekly) was administered while background pericarditis medications were discontinued. Clinical responders on rilonacept monotherapy were then randomized 1:1 to placebo or continued rilonacept in an event-driven double-blind RW period. Primary efficacy endpoint: time-to-first adjudicated pericarditis recurrence. Pts experiencing an eligible RP event during RW could receive open-label (OL) bailout rilonacept and remain on study.

Results: Etiology: idiopathic (85%), post-cardiac injury (15%).

Baseline characteristics (mean): disease duration was 2.4 years, with 4.7 lifetime episodes and 4.4 episodes/year.

Qualifying episode: pericarditis medications ─ NSAIDs (67%), colchicine (80%), and CS (49%). Mean pericarditis pain (11-point NRS scale) was 6.2, and mean C-reactive protein (CRP) was 6.18 mg/dL.

RI: 92% of pts completed RI; medians: time to NRS score ≤2 was 5 days; time to CRP normalization (≤0.5 mg/dL) was 7 days; time to Treatment Response was 5 days; time to monotherapy rilonacept was 7.9 weeks.

RW: 25 adjudicated events accrued in 61 randomized pts (Figure). Median time to event: placebo 8.6 wks, rilonacept Not-Estimable due to few events; HR 0.04 (96% risk reduction) (p < 0.0001). All 3 major secondary efficacy endpoints (Wk 16) were significant: maintained Clinical Response (rilonacept 81% vs. placebo 20% [p=0.0002]); absent/minimal pericarditis symptoms on 7-point Patient Global Impression of Pericarditis Severity scale (rilonacept 81% vs. placebo 25% [p=0.0006]); % of days with none/minimal pericarditis pain (rilonacept 98% vs. placebo 46% [p < 0.0001]).

No subsequent RP events were documented in pts on OL bailout rilonacept. 74 of 75 eligible pts continue OL rilonacept in a long-term extension up to 24 months.

Rilonacept was well-tolerated; 4 discontinuations in RI for AEs; SAEs: rilonacept (n=4), placebo (n=1), none drug-related; 1 withdrawn consent in RW.

Conclusion: Rilonacept (IL-1α/IL-1β trap) provided rapid and sustained reductions in pain and CRP as soon as after the first dose. Rilonacept monotherapy reduced RP event risk by 96% vs placebo. Rilonacept may provide a targeted therapeutic option for patients with RP.

Figure. Time to First CEC-Adjudicated Pericarditis Recurrence

Disclosures: A. Klein, Kiniksa, 1, 5, Sobi, 1, Pfizer, 1; M. Imazio, Kiniksa, 1, Sobi, 1; P. Cremer, Kiniksa, 5, 12, personal fees, Novartis, 5, Sobi, 12, personal fees; A. Brucato, Kiniksa, 12, My institution received funding from Kiniksa as an investigative site to run the study, Sobi, 5, Acarpia, 5; A. Abbate, Kiniksa, 5, Olatec, 5, 12, personal fees, Serpin, 5, 12, personal fees, Novartis, 5, 12, personal fees, Novo-Nordisk, 12, personal fees, Cromos Pharma, 12, personal fees, Janssen, 5, 12, personal fees; F. Fang, Kiniksa Pharmaceuticals Corp., 3, 11; A. Insalaco, None; M. LeWinter, Kiniksa, 5, 12, personal fees; B. Lewis, Kiniksa, 12, personal fees; D. Lin, Regeneron, 12, fees; S. Luis, Kiniksa, 1, Sobi, 1, 2, Medtronic, 2; S. Nicholls, Kiniksa, 5, 12, personal fees, AstraZeneca, 2, 5, Amgen, 5, Anthera, 2, 5, Eli Lilly, 2, 5, Esperion, 2, 5, Novartis, 5, Cerenis, 5, The Medicines Company, 5, Resverlogix, 2, 5, InfraReDx, 5, Roche, 5, Sanofi-Regeneron, 2, 5, Liposcience, 5, Akcea, 2, Omthera, 2, Merck, 2, Takeda, 2, CSL Behring, 2, Boehringer Ingelheim, 2; A. Pano, Kiniksa Pharmaceuticals Corp., 3, 11; A. Wheeler, Kiniksa Pharmaceuticals, Ltd., 2; L. Zou, Kiniksa Pharmaceuticals Corp., 3, 11; J. Paolini, Kiniksa Pharmaceuticals Corp., 2, 10, 11.

To cite this abstract in AMA style:

Klein A, Imazio M, Cremer P, Brucato A, Abbate A, Fang F, Insalaco A, LeWinter M, Lewis B, Lin D, Luis S, Nicholls S, Pano A, Wheeler A, Zou L, Paolini J. RHAPSODY: Rilonacept, an IL-1α and IL-1β Trap, Resolves Pericarditis Episodes and Reduces Risk of Recurrence in a Phase 3 Trial of Patients with Recurrent Pericarditis [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/rhapsody-rilonacept-an-il-1%ce%b1-and-il-1%ce%b2-trap-resolves-pericarditis-episodes-and-reduces-risk-of-recurrence-in-a-phase-3-trial-of-patients-with-recurrent-pericarditis/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/rhapsody-rilonacept-an-il-1%ce%b1-and-il-1%ce%b2-trap-resolves-pericarditis-episodes-and-reduces-risk-of-recurrence-in-a-phase-3-trial-of-patients-with-recurrent-pericarditis/