Background/Purpose: Goflikicept (GFC; RPH-104) is a novel fusion protein inhibiting interleukin-1 (IL-1). This study aimed to investigate its efficacy and safety in IL-1β-driven monogenic autoinflammatory disorder of Familial Mediterranean Fever (FMF).

Methods: Adult patients with FMF who were resistant or intolerant to colchicine and had ongoing attacks were randomized in the international, multicenter phase 2 double-blinded study to receive GFC subcutaneously in a dose of 160 mg (day 0), 80 mg (day 7), 80 mg (day 14), and 80 mg every 2 weeks (q2w) thereafter or matching injections of placebo for 16 weeks. Marker attack was defined as the combination of Physician Global Assessment (PGA) ≥2 and CRP >10 mg/l. If the marker FMF attack was not resolved or a recurrent attack occurred, the patients were unblinded, and those on placebo switched to GFC. The primary endpoint was a proportion of patients with complete treatment response (marker attack resolution and development of no new attacks).

Results: In total, 28 patients were randomized. Of them, 24 patients completed the study per protocol, 4 patients discontinued treatment prematurely, and 3 of them were in the GFC arm: 1 due to prohibited treatment; 1 due to lack of efficacy; 1 due to an adverse event (AE). The complete response was achieved in 9 (64.3%) patients in the GFC arm and in 1 (7.1%) patient in the placebo arm (p=0.004). No recurrent attack occurred after switching from placebo to GFC in 12 of 13 patients (92%). Minimal or no disease activity (PGA < 2) and CRP decrease ≤10 mg/l were achieved in the majority of patients in the GFC arm but not in the placebo arm (Fig. 1, Fig. 2). At least one AE was reported in 11 (78.6%) patients in the GFC arm, in 3 (21.4%) patients in the placebo arm, and in 8 (61.5%) patients who were switched from placebo to GFC. The majority of AEs were mild to moderate in severity. In one patient (switched from placebo to GFC), there was a serious AE of inflammation during the safety follow-up period. In one of the GFC arm patients, diarrhea led to premature treatment discontinuation. GFC treatment was safe and overall well tolerated. Safety profile of GFC was consistent with other IL-1 inhibitors; no new safety signals were reported.

Conclusion: GFC provided a significant improvement in the disease activity of colchicine-refractory/intolerant FMF patients compared to placebo, and its safety profile was similar to other IL-1 inhibitors.

Figure 1. Proportion of subjects with minimal disease activity/ inactive disease (PGA score < 2) during the treatment period

Figure 2. Proportion of subjects with CRP ≤ 10 mg/L during the treatment period

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/interim-results-of-a-randomized-placebo-controlled-study-of-il-1-inhibitor-goflikicept-in-patients-with-familial-mediterranean-fever/