Op0045 treatment of Idiopathic Recurrent Pericarditis With Goflikicept - First Data From the Interim Analysis of Phase 2/3 Ongoing Study

Abstract

BackgroundIdiopathic recurrent pericarditis (IRP) is a rare autoinflammatory disease [1,2] that has similar pathogenesis with adult-onset Still’s disease and monogenic autoinflammatory diseases [3,4]. IL-1α and IL-1β are the pivotal cytokines in the pathophysiology of acute pericarditis and its recurrence [5]. This report presents the interim analysis of clinical trial with goflkicept (original, fusion protein, heterodimer, binding IL-1α and IL-1β) in patients with IRP. Trial registration: ClinicalTrials.gov, NCT04692766.ObjectivesTo evaluate the efficacy and safety of goflikicept treatment in patients with IRP.MethodsSubjects with recurrence (n=9) or in inter-recurrence period (n=13) were enrolled in the run-in period of 12 weeks for treatment with NSAIDs and/or colchicine or 24 weeks for treatment with corticosteroids (CS).Dose finding approach was applied, where subjects from the first cohort (n=10) received subcutaneous goflikicept 80 mg every 2 weeks, subjects from the second cohort (n=12) - 240 mg load within the first week, 80 mg within the seсond week, thereafter 80 mg every 2 weeks on top of background NSAIDs, colchicine and/or CS. Treatment response is considered as an achievement or maintenance of the following criteria: chest pain NRS≤3, CRP≤5 mg/L, absent or mild (<10 mm) pericardial effusion on Day 14. In responders NSAIDs/colchicine were stopped immediately, CS therapy was reduced and terminated within 12 weeks and for the next 12 weeks patients were on goflikicept monotherapy. At the end of the run-in responders proceeded into the double-blind, placebo-controlled randomized-withdrawal (RW) period, where received goflikicept 80 mg every 2 weeks or placebo. Primary endpoint was the time to the first pericarditis recurrence. In case of recurrence, the patients were unblinded, patients from placebo group retreated with goflikicept. According to interim analysis plan efficacy/safety analysis included only unblinded data during the RW period.ResultsTreatment response was achieved in 8 of 9 patients, enrolled with recurrence and all patients enrolled without recurrence remained in remission at Day 4. There were no new recurrence events on goflikicept therapy, despite NSAIDs/colchicine/CS discontinuation during the run-in period. In the run-in period mean NRS, CRP and pericardial effusion decreased from baseline (Figure 1). Decrease of concentrations of IL-1RA, IL-6, calprotectin was reported during the run-in period, which confirms anti-inflammatory effect of goflikicept. A total of 20 patients were randomized. Recurrent pericarditis occurred in 8 of 10 patients in placebo group, there were no recurrence events in goflikicept group to the moment of this interim analysis. After retreatment with goflikicept and recurrence resolution there were no new recurrence events. Adverse events (AEs) occurred in 15 of 22 patients (68,2%) during the run in period. During the run- in period, 6 of 22 patients (27%) experienced infections, 4 (18,2%) cholesterol elevation, 3 (13,6%) lymphopenia, 2 (9,1%) lipase elevation, 2 (9,1%) injection site reactions. AEs occurred in 4 of 8 patients (50%) during placebo treatment in the RW period. AEs occurred in 6 of 8 patients (75%) after retreatment with goflikicept. There were no deaths, no new safety signals. Overall safety profile was similar to those described for other IL-1 blockers.ConclusionThe first data show ability to achieve and maintain IRP remission on goflikicept monotherapy with favorable risk-benefit ratio. Final data will be provided.References[1]www.orpha.net. Assessed January 14, 2022[2]Blank N, Lorenz HM. Current Rheumatology Reports (2018)21:18[3]Imazio M. Heart. 2011 Nov;97(22)1882-92[4]Calabuig IJ, Sanches Soriano RM, Marco Domingo TF et al. Rev Esp Cardiol. 2017;70(3):208–219[5]Imazio M, Lazaros G, Gattorno M. European Heart Journal 2021 Epub ahead of print. PMID: 34528670AcknowledgementsThis study is sponsored by R-Pharm JSC.Disclosure of InterestsAlexey Maslyanskiy Consultant of: R-Pharm, Valentina Myachikova Speakers bureau: Novartis, Sobi, Olga Moiseeva Speakers bureau: Bayer, Janssen, Pfizer, Oksana Vinogradova Speakers bureau: AstraZeneca, Ekaterina Gleykina Speakers bureau: Bayer,Johnson & Johnson, AstraZeneca, Pfizer, Yan Lavrovsky Employee of: R-Pharm Overseas Inc, Sergey Grishin Employee of: R-Pharm JSC, Dmitry Salazanov Employee of: R-Pharm JSC, DARIA BUKHANOVA Employee of: R-Pharm JSC, Alina Egorova Employee of: R-Pharm JSC, Margarita Shchedrova Employee of: Employee of R-Pharm JSC, Mikhail Samsonov Employee of: R-Pharm JSC.

Interleukin-1 blockers for the treatment of recurrent pericarditis: pathophysiology, patient reported outcomes and perspectives

“…38 Early data from an ongoing phase 2/3 study looking at goflikicept, a heterodimer binding both IL-1α and IL-1β, in patients with idiopathic RP showed an ability to achieve and maintain remission even after background therapy was weaned. 39 There were no recurrence events in the goflikicept group during the interim analysis, and the safety profile was similar to other IL-1 blockers. 39…”

“…39 There were no recurrence events in the goflikicept group during the interim analysis, and the safety profile was similar to other IL-1 blockers. 39…”

Novel Therapeutic Insights Into the Treatment of Pericarditis: Targeting the Innate Immune System

“…The safety profile is similar to those of the other IL-1 blockers. 59,60 The striking results of the IL-1 blockers (anakinra, rilonacept, and goflikicept) in patients who are colchicineresistant, with or without glucocorticoid dependence, provide a paradigm shift in the treatment of recurrent pericarditis. These data are also supported by translational research that used a novel murine model of AP to study in more detail the role of the NLRP3 inflammasome/IL-1b axis in the pathophysiology of acute and recurrent pericarditis.…”