Sutimlimab Is Effective, Well Tolerated in Refractory Chronic Immune Thrombocytopenia

Sutimlimab demonstrated rapid efficacy in the study cohort, and platelet level improvements were sustained for the duration of treatment in nearly half of the participants.

Preventing and resolving bleeding are main treatment goals in chronic immune thrombocytopenia (ITP). Although several therapeutic options targeting known disease mechanisms are available, a significant subset of patients are unresponsive to therapy. A recent study found that sutimlimab, a drug approved for use in cold agglutinin disease (CAD), was well tolerated and associated with positive responses in patients with refractory chronic ITP.

ITP is rare condition associated with a high bleeding risk due to increased platelet destruction and/or decreased platelet production. The condition’s pathophysiology is heterogeneous, and available treatments target several pathways that may contribute to thrombocytopenia in patients with primary ITP.

“Preclinical and clinical evidence supports a role of classical pathway activation in ITP. Approximately 50% of patients with ITP have autoantibodies that activate complement or have complement proteins detectable on the platelet surface,” the authors wrote. Anticomplement therapies are hypothesized to increase platelet counts in individuals with ITP, particularly in cases of severe or refractory ITP, and a case report supports this possibility.

Sutimlimab, a humanized monoclonal immunoglobulin (Ig)-G4 antibody, selectively targets complement C1s to block classical complement pathway activation. The drug is currently approved for the treatment of CAD, and the CARDINAL and CADENZA studies showed it to stop hemolysis quickly, increase hemoglobin levels, and reduce fatigue in this disease setting.

Results of the phase 1, single-arm, open-label study of sutimlimab in ITP were published in Blood Advances. The study comprised 2 parts: (1) an initial 11-dose treatment period lasting up to 21 weeks, followed by a safety follow-up/washout period of up to 9 weeks, and (2) an extension period when eligible patients were treated again and received sutimlimab until the last patient enrolled had received at least 52 additional weeks of treatment. The study assessed the safety and efficacy of biweekly sutimlimab as well as its pharmacokinetics and pharmacodynamics in refractory chronic ITP.

The study included 12 patients with a median age of 42 years, all of whom had inadequate responses to 2 or more lines of therapy for chronic ITP, defined as a platelet count of 30 x 109/L or lower ahead of Part 1. Seven of the 12 patients from Part 1 were eligible for Part 2, and the median length of retreatment in this portion was 113 weeks. Eligibility criteria for the second part of the study included receiving at least 1 dose of sutimlimab in the first part of the study and showing evidence of treatment efficacy, defined as a platelet count higher than 30 x 109/L on multiple occasions or a platelet count twice as high as baseline levels. Participants showing evidence of ongoing or recurrent thrombocytopenia during the Part 1 safety follow-up/washout period were also eligible for Part 2.

In Part 1, the mean platelet count increase among the 12 eligible patients was 25 x 109/L at baseline to 54 x 109/L at 24 hours after sutimlimab treatment commenced. Those who responded to treatment also maintained platelet counts of at least 50 x 109/L throughout the first part of the study. Five patients showed durable platelet counts of at least 50 x 109/L during at least half of their follow-up visits, and 4 reached complete response, defined as a platelet count of at least 100 x 109/L. Four patients discontinued treatment due to nonresponse or a need for rescue therapy in Part 1.

In all patients, platelet counts returned to baseline levels during the washout period after Part 1 of the study. In Part 2, mean platelet counts increased quickly once treatment restarted, and patients demonstrated platelet counts on par with previous responses to sutimlimab during Part 1. Three patients discontinued therapy during Part 2 of the study: 2 due to unresponsiveness as determined by physicians and 1 on the subject’s own accord.

In Part 1 of the study, there were 74 treatment-emergent adverse events (TEAEs), the most common of which was fatigue. Of the TEAEs, 21 events in 6 patients were considered sutimlimab related. There were 4 serious TEAEs reported, and 1 (migraine) was attributed to sutimlimab.

Overall, sutimlimab demonstrated significant efficacy on a rapid timeline in the study cohort, and platelet level increases were sustained for the duration of treatment in nearly half of the participants. The outcomes were achieved sans concomitant therapy for ITP. Although the study’s size and single-arm design are limitations, the study population represented a difficult-to-treat subset of patients with a rare condition.

“These results demonstrate that C1s inhibition can be an effective therapeutic approach for patients who have failed other therapies and support the hypothesis that activation of the classical complement pathway contributes to the clinical heterogeneity of ITP,” the authors concluded. “Furthermore, the findings of this study support further development of anti-C1s inhibitor for patients with ITP that is not responsive to currently available therapies.”


Broome CM, Röth A, Kuter DJ, et al. Safety and efficacy of classical complement pathway inhibition with sutimlimab in chronic immune thrombocytopenia. Blood Adv. Published online August 16, 2022. doi:10.1182/bloodadvances.2021006864