New Evidence Emerges on Narsoplimab’s Therapeutic Potential in TA-TMA

New findings published in Blood Advances suggest that the monoclonal antibody narsoplimab (OMS721) may offer a survival advantage in hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA), a potentially fatal complication of hematopoietic cell transplantation (HCT).¹

Comparing the overall survival (OS) of narsoplimab-treated patients with high-risk TA-TMA pooled across 2 cohorts (n = 77) vs untreated patients from an external control cohort (n = 121), those treated with narsoplimab had an approximately 72% lower mortality risk, corresponding to roughly a quarter the risk of death observed in untreated patients (HR, 0.28; 95% CI, 0.22-0.37; P <.0001).

TA-TMA is a serious multisystem complication of HCT for which there is currently no approved treatment. Narsoplimab is an investigational drug for treatment of TA-TMA that has previously demonstrated promising clinical activity in the single-arm, open-label phase 2 trial OMS721-TMA-001 (NCT02222545).² Resubmission of a biologics license application for use in TA-TMA is under FDA review after the agency issued a complete response letter following initial application.

This observational study sought to validate and expand upon existing evidence by performing statistical comparisons to a control group. While the retrospective nature of analysis was a limitation cited by the authors, these data provide clarified insights into a therapy that may improve outcomes in this rare complication.

What cohorts and patients were included for comparison?

This study examined 3 retrospective cohorts of patients with high-risk TA-TMA, including 2 cohorts of patients treated with narsoplimab compared separately and jointly against a well-matched external control cohort, resulting in 3 sets of comparative analyses. Investigators compared OS, defined as the time to death from date of TA-TMA diagnosis, using Cox proportional hazards models.

To ensure cross-cohort comparability, the study’s inclusion criteria aimed to capture those at high risk for poor outcomes or death. Across all 3 cohorts, patients were required to have at least 1 of the following risk factors for inclusion: elevated lactate dehydrogenase (LDH) 2 or more times upper limit of normal (ULN), acute graft-vs-host-disease (GVHD) grade 2 to 4, organ dysfunction (renal, pulmonary, and/or neurological), and systemic infection.

Data for the first narsoplimab-treated cohort were obtained from the OMS721-TMA-001 trial, a study completed in 2020 that enrolled patients who underwent allogeneic HCT and were diagnosed with TA-TMA.² The treatment regimen in this trial entailed intravenous narsoplimab once weekly for 4 to 8 weeks. A total of 28 patients from this trial were included in the present study, all of whom had met at least 2 of the high-risk inclusion criteria associated with poor prognosis.

The second treatment cohort was sourced from a narsoplimab expanded access program (EAP), which provided access to narsoplimab for patients with TA-TMA who had no other treatment options or access to clinical trials. In this program, patients received narsoplimab 2 to 3 times weekly. Only patients who received at least 1 dose of narsoplimab in the first line as of October 2023 met at least 1 of the high-risk criteria, and reported no prior treatment (eg, eculizumab, ravulizumab, pegcetacoplan, and/or defibrotide) for TA-TMA were included in the present study’s analyses (n = 49).

The external control cohort was derived from the Kyoto Stem Cell Transplantation Group (KSCTG) registry, which includes data for patients who were at least aged 16 years and who received an allogeneic HCT between 2000 and 2016 from 17 sites across Japan. For the analysis, only patients diagnosed with TA-TMA were included (n = 121). Of these 121 patients, 111 demonstrated 2 or more high-risk features and were consequently used as the control group in the comparative analysis with the OMS721-TMA-001 cohort. All 121 patients served as the control in comparisons against the EAP cohort and in the pooled narsoplimab-treated cohort.

What additional findings were reported?

The aforementioned findings from the pooled comparative analysis are substantiated by findings from the 2 nonpooled analyses. Here, similar patterns in mortality risk reductions were achieved in the narsoplimab-treated single-arm trial cohort (HR, 0.25; 95% CI, 0.19-0.34; P <.0001) and EAP cohort (HR, 0.38; 95% CI, 0.22-0.37; P <.0001) vs the KSCTG control cohort.

Stratifying outcomes by risk factor revealed further 1-year survival improvements with narsoplimab treatment compared with no treatment, namely in patients with elevated LDH ≥2 ULN (50.3% vs 11.4%; P =.0002), acute GVHD (54.5% vs 16.2%; P <.001), organ dysfunction (45.9% vs 11.0%; P <.0001), and infection (35.2% vs 16.6%; P =.0014).

“Collectively, these results provide strong evidence of a survival benefit associated with narsoplimab treatment in patients with high-risk TA-TMA,” stated investigators, Matsui et al, in their conclusion.¹

REFERENCES:

1. Matsui H, Arai Y, Kanda J, et al. Survival in adults with high risk TA-TMA - a comparative analysis of narsoplimab versus supportive care. Blood Adv. Published online October 10, 2025. doi:10.1182/bloodadvances.2025017540

2. Safety and efficacy study of OMS721 in patients with thrombotic microangiopathies. ClinicalTrials.gov. Updated August 28, 2024. Accessed October 25, 2025. https://clinicaltrials.gov/study/NCT02222545