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First-in-class antibody sutimlimab selectively inhibits classical complement pathway

Presented by
Dr Catherine Broome, MedStar Georgetown University Hospital, Washington DC, USA
ASH 2020
Phase 1
Interim results of an ongoing phase 1b trial with sutimlimab provided additional evidence that the complement pathway plays an important role in immune thrombocytopenia (ITP). A rapid and durable response was elicited and maintained, with an acceptable safety profile [1].

Some patients with ITP display partial response or no response to currently approved treatment protocols. Dr Catherine Broome (MedStar Georgetown University Hospital, Washington DC, USA) and colleagues hypothesised that a primary mechanism of thrombocytopenia in a subset of patients with ITP is classical complement pathway-dependent and that inhibition with sutimlimab would improve thrombocytopenia. Sutimlimab is a first-in-class humanised monoclonal antibody that selectively inhibits activation of the complement pathway by binding to complement protein 1 (C1).

An open-label phase 1b study (NCT03275454) included 12 patients with chronic ITP, many of those previously received a thrombopoietin receptor agonist (TPO-RA), rituximab, and splenectomy. In the first part of the trial, participants received sutimlimab on days 0 and 7, after which they received the medication biweekly for a maximum of 21 weeks, followed by a 9-week washout phase. If a clinically meaningful response was elicited from the first part of the trial, patients were included in a long-term extension phase.

Interim data demonstrated that sutimlimab resulted in a rapid and sustained response, with mean platelet count increasing to >50 ├Ś 109/L by day 1. This response was maintained for the duration of the treatment. Overall, 5 patients achieved durable response with sutimlimab as monotherapy; 4 patients had to be removed because they either needed rescue therapy or were unresponsive to sutimlimab.

Washout kinetics demonstrated that thrombocytopenia reoccurred when sutimlimab was discontinued and resolved upon retreatment in the long-term extension phase, corroborating the observed clinical effects of classical complement pathway inhibition. The therapeutic effect of sutimlimab was sustained during the long-term extension to week 79.

  1. Broome CM, et al. Long-Term Safety and Efficacy of Sutimlimab in Patients with Chronic Immune Thrombocytopenia. 62nd ASH Annual Meeting, 5-8 December 2020. Abstract 23.

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