お知らせ • Feb 20
Omeros Announces Robust Results for Narsoplimab Expanded Access Program in TA-TMA
Omeros Corporation announced statistical analysis results related to the expanded access program (EAP) for narsoplimab, Omeros’ first-in-class monoclonal antibody inhibiting the lectin pathway of complement, in the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA), a life-threatening complication in both adult and pediatric hematopoietic stem cell transplantation (HSCT). These latest analyses, conducted by an independent statistical group, comprise multiple survival comparisons between narsoplimab-treated EAP patients and similarly at-risk TA-TMA patients in the external control registry. The results from these analyses further support the robustness of the previously reported results from the statistical analysis plan agreed with FDA, with representative analyses of the combined EAP and pivotal trial patients yielding hazard ratios ranging from 0.34 (95% confidence interval: 0.21, 0.53) to 0.46 (95% confidence interval: 0.35, 0.60) and p-values ranging from less than 0.00001 to 0.00002. Consistent with all previous clinical experience with narsoplimab, no safety signals of concern were observed. As reported on December 19, 2024 and January 15, 2025, narsoplimab met its primary endpoint, with TA-TMA patients in its OMS721-TMA-001 pivotal trial demonstrating clinically meaningful and statistically significant superiority in overall survival – a hazard ratio of 0.32 (95% confidence interval: 0.23 to 0.44) with p-value less than 0.00001 – compared to the TA-TMA patients in the external control registry, with the prespecified primary-related sensitivity analyses strongly supporting the robustness of the primary analysis results. Today’s announcement reports the results of this same set of analyses on patients treated with narsoplimab in the EAP. Overall survival in the primary, primary-related, and EAP-related analyses includes an adjustment for immortal time bias. The narsoplimab EAP population at time of database lock included 136 TA-TMA patients, 128 of whom had received allogeneic versus autologous stem cell transplants. Of those allogeneic graft recipients, 84 were adult (at least 16 years of age) and 44 were children. TA-TMA risk factors are not available for all EAP patients; based on available information and using the international expert consensus criteria for high risk of death (Schoettler et al, 2023), 102 patients (65 adults and 37 children) were characterized as having “high-risk” TA-TMA, with 82% of adults and 86% of children having multiple risk factors for death. Of the 102 high-risk EAP patients, 49 adults and 13 children had received no treatment prior to narsoplimab. The narsoplimab pivotal trial (OMS721-TMA-001) enrolled 28 adult allogeneic transplant patients with high-risk TA-TMA, none of whom received prior treatment for TA-TMA. The external control registry is comprised of 121 adult patients (defined by the registry as 16 years of age or older) who underwent allogeneic transplant and developed high-risk TA-TMA, none of whom received narsoplimab, any other complement inhibitor treatment, or defibrotide. The following are representative analyses, conducted by the independent statistical group, of the 77 (49 EAP and 28 OMS721-TMA-001) allogeneic HSCT, previously untreated, high-risk adult patients who received narsoplimab compared to similarly at-risk external control registry patients; the first is the same as the previously reported primary analysis and the subsequent 4 are the same as the previously reported primary-related sensitivity analyses, all of which were prespecified in the FDA-agreed statistical analysis plan: Overall survival using Inverse Probability of Treatment Weighting (IPTW) with all specified risk factors: Hazard ratio = 0.37 (95% confidence interval: 0.28, 0.48), P-value, Overall survival using IPTW with only treatment as a factor: Hazard ratio = 0.46 (95% confidence interval: 0.35, 0.60), P-value, Testing proportional hazards assumptions using IPTW in a sequence of four models in which patient follow-up is truncated at 100 days, 6 months, 1 year, and 2 years: 100 days: Hazard ratio = 0.46 (95% confidence interval: 0.33, 0.63), P-value, 6 months: Hazard ratio = 0.40 (95% confidence interval: 0.29, 0.54), P-value. 1 year: Hazard ratio = 0.37 (95% confidence interval: 0.28, 0.50), P-value: 2 years: Hazard ratio = 0.36 (95% confidence interval: 0.27, 0.48), P-value: Overall survival using IPTW with day zero for the external control registry patients set at the median time between the date of TA-TMA diagnosis and the date of narsoplimab treatment initiation for the patients in the combined EAP and OMS721-TMA-001 pivotal trial population: Hazard ratio = 0.36 (95% confidence interval: 0.28, 0.48), P-value. Overall survival with and without all specified risk factors (RFs) using 1:1 propensity score matching (combined EAP and OMS721-TMA-001 trial patients versus external control registry patients): 1:1 with RFs: Hazard ratio = 0.34 (95% confidence interval: 0.21, 0.53), P-value, 1:1 w/out RFs: Hazard ratio = 0.39 (95% confidence interval: 0.26, 0.60), P-value = 0.00002. In the previously reported primary and primary-related sensitivity analyses, this analysis included 1:2 propensity score matching. The 121 external control patients, however, do not allow for 1:2 matching vs. 77 narsoplimab-treated patients. Sixteen adult and 20 pediatric allogeneic-transplant EAP patients with high-risk TA-TMA had failed treatment with one or more regimens of eculizumab, ravulizumab, pegcetacoplan, and/or defibrotide prior to administration of narsoplimab. Less than 20% of patients who fail these treatments are reported to reach 1-year survival. Despite this historically poor expectation, narsoplimab treatment showed the following 1-year survival in previously treated high-risk EAP patients: All: 44%, Adult: 41%, Children: 47%. In the EAP, 49 adult and 13 pediatric allogeneic-transplant patients with high-risk TA-TMA did not receive complement C5 (e.g., eculizumab, ravulizumab), C3 inhibitors (e.g., pegcetacoplan), or defibrotide prior to treatment with narsoplimab. One-year survival in these patients is: All: 62%, Adult: 58%, Children: 79%.
