Sutimlimab Among Patients With Chronic/Refractory Immune Thrombocytopenia

Results from a Phase 1 Multicenter Trial

According to findings from a phase 1 trial recently published in Blood Advances, sutimlimab, through its selective inhibition of the classical complement pathway, improved platelet counts and demonstrated a manageable safety profile among patients with chronic/refractory immune thrombocytopenia (ITP). 

ITP is a rare and high-risk autoimmune disease and is characterized by increased platelet destruction and/or impaired platelet production. Patients with ITP often experience a high risk of bleeding, an increased mortality rate, and a decreased quality of life. Despite there being treatment available for patients with ITP, up to 20% of patients remain refractory, or unresponsive, to treatment. 

According to Catherine M. Broome, MD, MedStar Georgetown University Hospital, Washington, DC, and coauthors, a “mechanism that may contribute to the disease refractoriness is antigen-antibody complex-mediated activation of the complement system, a cascade of proteins mediating both innate and adaptive immunity.” 

To expand research on possible treatments that may counteract disease refractoriness, Dr Broome et al aimed to study sutimlimab, a first-in-class, monoclonal IgG4 antibody which selectively inhibits C1s and prevents classical complement pathway activation. The study authors aimed to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of sutimlimab among patients with chronic/refractory ITP. 

12 patients with chronic/refractory ITP who had an inadequate response to 2 or more prior therapies and a platelet count of ≤ 30 × 10⁹/L were enrolled in this study. Patients received sutimlimab for a median duration of 20.5 weeks, followed by a 2-week washout period, in part A. In part B, 7 out of 12 patients received sutimlimab retreatment for a median duration of 113 weeks. 

In part A, the standard deviation in platelet count increased from 25 × 10⁹/L (17) to 54 × 10⁹/L (60) 24 hours after starting sutimlimab, and maintained ≥50 × 10⁹/L throughout the rest of part A. 42% of participants (n=5) achieved durable platelet count responses, with platelet counts of  ≥50 × 10⁹/L in 50% or more of follow-up visits. 4 patients achieved complete response, or a platelet count of ≥100 × 10⁹/L. In the 2-week washout period, the mean platelet count returned to baseline levels but increased again upon retreatment in part B. 

In terms of safety, 74 treatment-related adverse events were observed in part A (n=10) and 70 were observed in part B (n=6). Among these events, 5 were serious, and only 1 event (migraine) was attributed directly to sutimlimab. 

Dr Broome et al concluded, “Sutimlimab was associated with a rapid, sustained, and repeatable increase in the mean platelet count in 42% of the patients with chronic/refractory ITP. These results demonstrated 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.” 

Source: 

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