Kiniksa Announces Rilonacept Interim Phase 2 Clinical Data; Initiates Pivotal Phase 3 Clinical Trial

Kiniksa Pharmaceuticals, Ltd.recently announced interim data from an open-label Phase 2 clinical trial of rilonacept, a weekly, subcutaneously-injected, recombinant fusion protein that blocks IL-1α and IL-1β signaling, in subjects with symptomatic recurrent pericarditis. The data show reductions in both inflammation and reported pain after the first dose which persisted throughout the treatment period. The company also reported that it has initiated RHAPSODY, a pivotal Phase 3 clinical trial in recurrent pericarditis, and is actively recruiting and screening subjects.

“We are focused on rapidly developing rilonacept in recurrent pericarditis as a potential treatment for this unmet medical need,” said Sanj K. Patel, Chief Executive Officer and Chairman of the Board of Kiniksa. “Pericarditis is a debilitating disease where recurrence leads to higher risk of relapse and impacts quality of life. Rilonacept has the potential to be the first approved therapy for patients suffering from recurrent pericarditis.”

Kiniksa recently completed enrollment in an open-label Phase 2 pilot study, which is evaluating the treatment response to rilonacept in subjects with both symptomatic recurrent pericarditis as well as other patient subsets within pericarditis, including asymptomatic steroid-dependent subjects with recurrent pericarditis and subjects with post-pericardiotomy syndrome. In this study, all subjects receive a loading dose of rilonacept 320 mg subcutaneously (SC) followed by 160 mg SC weekly maintenance on top of any combination of co-administered nonsteroidal anti-inflammatory drugs (NSAIDs) and/or colchicine and/or corticosteroids during a 6-week base treatment period. An optional 18-week extension period follows during which weaning off of concomitant NSAIDs, colchicine and corticosteroids is allowed. The assessed efficacy outcomes measures include an 11-point pain Numerical Rating Scale (NRS), C-reactive protein (CRP), electrocardiogram (ECG), and size of pericardial effusion. The co-principal investigators are Dr. Allan Klein of Cleveland Clinic and Dr. David Lin of Minneapolis Heart Institute Foundation.

As of November 1, 12 subjects, each with at least 3 episodes of pericarditis and elevated CRP (>1mg/dL), enrolled in a 6-week base treatment period. Results showed a reduction in both inflammation and reported pain after the first dose and a persistent clinical response throughout the 6-week base treatment period:

-mean patient-reported pericardial pain on an 11-point NRS decreased from 4.6 at baseline to 0.9 at 6 weeks;

-mean CRP decreased from 4.9 mg/dL at baseline to 0.37 mg/dL at 6 weeks; median time to CRP normalization was 9 days; and

-pericardial signs resolved, including pericardial effusion (5/6 subjects), PR depression (3/4 subjects), widespread ST elevation (2/2 subjects), and pericardial rub (3/3 subjects).

As of November 1, 10 of the 12 enrolled subjects received at least 6 weeks of treatment with rilonacept, 6 continued into the optional 18-week extension period, and 4 completed 24 weeks of treatment. These 10 subjects exhibited a continued clinical response to rilonacept as described below:

-mean patient-reported pericardial pain on an 11-point NRS further decreased to 0.3, and mean CRP was 0.44 mg/dL at 24 weeks;

-the pericardial effusion in the 1 remaining subject resolved during the extension period; and

-of the 4 subjects on corticosteroids at baseline, the 1 subject who had completed 24 weeks of treatment successfully tapered off corticosteroids.

Rilonacept has been generally well-tolerated in the study, with adverse events (AEs) consistent with the US FDA-approved label for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome and Muckle-Wells Syndrome. The most common AEs were gastrointestinal disorders and injection site reactions. There was one treatment-related serious AE that resulted in discontinuation: a skin abscess which responded to medical treatment. Infections are reported in the rilonacept label for CAPS.

“We are pleased to announce the commencement of RHAPSODY, a pivotal Phase 3 clinical trial of rilonacept in recurrent pericarditis,” said John F. Paolini, MD, PhD, FACC, Chief Medical Officer of Kiniksa. “RHAPSODY was supported by the interim data from our Phase 2 pilot study, which showed that rilonacept provided a reduction in both inflammation and reported pain as well as a durability of response in subjects with a symptomatic recurrent pericarditis episode. We believe we are now closer to providing a potential treatment option for patients suffering from recurrent pericarditis, a disease with significant unmet medical need.”

Kiniksa has initiated RHAPSODY, a double‑blind, placebo‑controlled, randomized withdrawal (RW) study with an open‑label extension period, and is actively recruiting and screening subjects. The study is intended to evaluate the efficacy and safety of rilonacept treatment in subjects with recurrent pericarditis. The company expects that up to 50 subjects will be randomized into the RW period. Eligible subjects must present at screening with at least a third pericarditis episode, defined as at least 1 day with pericarditis pain of ≥ 4 on the 11-point NRS and a CRP value ≥ 1 mg/dL within the 7-day period prior to first study drug administration. Subjects included in the study may be receiving concomitant NSAIDs and/or colchicine and/or oral corticosteroid treatment in any combination. The primary efficacy endpoint is time-to-first-pericarditis-recurrence in the RW period. The Clinical Endpoint Committee will adjudicate all suspected pericarditis recurrences for inclusion in the primary efficacy endpoint analysis. The co-principal investigators are Dr. Allan Klein of Cleveland Clinic and Dr. Massimo Imazio of the University of Torino, Italy.

RHAPSODY is a pivotal Phase 3 clinical trial in recurrent pericarditis utilizing rilonacept. The study is comprised of 5 periods: a screening period; a single-blind run-in period during which subjects receive a loading dose of rilonacept 320 mg injected SC followed by 160 mg SC weekly while background pericarditis medications are tapered and discontinued; a double-blind, placebo-controlled 24-week RW period during which clinical responders to rilonacept are randomized 1:1 and receive 160 mg SC weekly rilonacept or placebo for at least 24 weeks; a long-term extension treatment period after trial completion during which all subjects completing the RW period have the option to receive up to 24 weeks of open-label rilonacept 160 mg SC weekly; and a long-term extension follow-up period during which all subjects in the long-term extension period will be followed for 24 weeks for safety and pericarditis recurrences.

Rilonacept is a weekly, subcutaneously-injected, recombinant fusion protein that blocks IL-1α and IL-1β signaling. Rilonacept was discovered and developed by Regeneron and is approved by the FDA under the brand name ARCALYST for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), which includes Familial Cold Autoinflammatory Syndrome and Muckle-Wells Syndrome. IL-1 blockade may interfere with immune response to infections. Serious, life-threatening infections have been reported in patients taking ARCALYST. ARCALYST should be discontinued if a patient develops a serious infection. Taking ARCALYST with TNF inhibitors is not recommended because this may increase the risk of serious infections. Kiniksa exclusively licensed rilonacept from Regeneron for recurrent pericarditis and certain other indications. Rilonacept in recurrent pericarditis is an investigational drug.

Kiniksa is a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients suffering from debilitating diseases with significant unmet medical need. Kiniksa has a pipeline of five product candidates across various stages of development, focused on autoinflammatory and autoimmune conditions. For more information, visit www.kiniksa.com.