Pivotal trial of OMS 721 shows efficacy in HSCT-TMA.- Omeros Corp

Narsoplimab, an inhibitor of mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway and activator of the coagulation cascade, is being studied for the treatment of HSCT-TMA patients at high risk for poor outcomes. Narsoplimab has been awarded Breakthrough Therapy designation by FDA and is the subject of a rolling Biologics License Application (BLA) for HSCT-TMA. The nonclinical and CMC modules of the rolling BLA have already been submitted, and the final sections of the clinical module are in the publishing phase during which finalized documents are electronically processed and integrated for submission in the format required by FDA. Omeros previously presented preliminary data from its pivotal HSCT-TMA trial. The final data reported are those that are included in the BLA. In the 28-patient single-arm, open-label pivotal trial in adult HSCT-TMA patients, treatment consisted of narsoplimab administered intravenously once weekly for up to 8 weeks with an extended follow-up period. The study’s patient population was very ill, with the large majority of study patients having multiple comorbidities at baseline (e.g., graft-versus-host disease, significant infections, multi-organ dysfunction, etc.). The FDA-agreed primary endpoint (complete response) required clinical improvement in TMA markers (platelet count and lactate dehydrogenase [LDH]) and in organ function (renal, pulmonary, gastrointestinal or neurological) or freedom from transfusion. Secondary endpoints included 100-day and overall survival as well as change from baseline for individual laboratory markers (platelets, LDH, haptoglobin, hemoglobin and creatinine). The final results on primary and key secondary endpoints include: 61% (95% CI: 40.6% to 78.5%) complete response rate (CRR) in the full analysis set (FAS; patient receiving at least one dose of narsoplimab; p<0.0001 compared to 15% efficacy threshold agreed with fda). also 74% (95% ci: 51.6% to 89.8%) crr in the per-protocol (pp) population (patients receiving the protocol-specified narsoplimab treatment for at least 4 weeks; p><0.0001 compared to the 15% threshold). in addition, 100-day survival was 68% in the fas, 83% in the pp population and 94% in complete responders. median overall survival was 274 days in the fas, 361 days in the pp population and, for complete responders, was not estimable (more than half of the responders were alive at last follow-up). similar responses were observed across all patient subgroups defined by baseline characteristics, transplant characteristics and transplant complications. the majority of individual laboratory markers showed statistically significant improvement with the remainder numerically improving. adverse events were typical of the post-hsct population (e.g., fever, diarrhea, vomiting, nausea and neutropenia) and no safety signal of concern was identified. six deaths occurred in the study, all from causes common in hsct.></0.0001></0.0001>