Positive data in pivotal trial of hematopoietic stem cell transplant- associated thrombotic microangiopathy patients treated with narsoplimab.-Omeros Corpn.

Omeros Corporation announced positive data from its pivotal clinical trial of the company�s novel investigational complement inhibitor narsoplimab in the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) , a frequently lethal complication of HSCT. These preliminary data were recently provided to FDA as part of the company�s ongoing interactions with the Agency on the narsoplimab Biologics License Application (BLA).

All safety and efficacy endpoints � including the composite primary endpoint and the secondary endpoints � are agreed with FDA. The reported data support a strongly positive benefit-risk balance. The primary efficacy endpoint in this single-arm open-label trial of HSCT-TMA patients is the proportion of patients who achieve a highly rigorous set of response criteria that requires both improvement in HSCT-TMA laboratory markers and improvement in clinical status (organ function and transfusions). Patients who did not fully meet these criteria were considered non-responders. The secondary endpoints include survival rates and change from baseline in HSCT-TMA laboratory markers. Consistent with the pre-specified statistical analysis plan for the trial, the primary and secondary endpoints are assessed for (1) all patients who received at least one dose of narsoplimab and (2) patients who received at least 4 weeks of narsoplimab dosing. Patients enrolled in this trial had a high expected mortality rate. In severe cases of HSCT-TMA, mortality can exceed 90 percent.

Primary Efficacy Endpoint: 56 percent of all patients receiving at least one dose of narsoplimab achieved complete responder status (met full set of FDA-agreed response criteria). 68 percent of patients who received the protocol-specified narsoplimab treatment of at least 4 weeks of dosing achieved complete responder status.

Secondary Endpoints : 1. 100-day survival following HSCT-TMA diagnosis for all patients receiving at least one dose of narsoplimab was 65 percent.2. 100-day survival following HSCT-TMA diagnosis for patients who received the protocol-specified treatment of at least 4 weeks of narsoplimab dosing was 81 percent. 3. 100-day survival following HSCT-TMA diagnosis in the complete responder group was 93 percent.4. Substantial and statistically significant improvements in platelet count, LDH and haptoglobin were observed across all of the following groups: All patients who received at least one dose of narsoplimab (p < 0.01 for each laboratory value). Patients who received protocol-specified treatment of at least 4 weeks of dosing (p ? 0.002 for each laboratory value) Complete responders (p < 0.001 for each laboratory value).5. Hemoglobin increased across all groups and reached statistical significance (p = 0.041) in complete responders. 6. Creatinine also improved meaningfully in all patient groups but did not reach statistical significance given the use of nephrotoxic agents in trial patients.

Safety : No signal of any serious safety risk has been observed with narsoplimab in the trial. The most common adverse events seen in this trial were nausea, vomiting, diarrhea, hypokalemia, neutropenia and fever � all common in stem-cell transplant patients. 21 percent of patients died during the trial due to causes common in stem cell transplant, with no additional patients discontinuing for adverse events. The data from the patients who died were not excluded from any analyses.

The HSCT-TMA patient population enrolled in this trial had multiple high-risk features that portend a poor outcome. These include persistence of HSCT-TMA despite modification of immunosuppression (which was a criterion for entry into the trial), graft-versus-host disease, significant infections, non-infectious pulmonary complications and neurological findings. Patients in the trial had a high expected death rate, with 93 percent of them having multiple risk factors. Patient enrollment in the pivotal trial has been completed. The details of the endpoints, including the response criteria agreed with FDA, and the number of patients in the trial remain confidential for competitive business reasons. Last year the company reported data on 19 HSCT-TMA patients treated with narsoplimab on which FDA granted breakthrough therapy designation. The results reported now are even stronger. The response rate remains equally high at 56 percent, while the 100-day survival has improved from 53 percent to 65 percent.