The FDA has accepted a Biologics License Application for narsoplimab and granted it Priority Review for use as treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy.
The FDA has accepted a Biologics License Application (BLA) for narsoplimab (OMS721) and granted it Priority Review for use as treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA). No advisory committee meeting will be held to discuss the BLA, announced by the Omeros Corporation, in a press release.1
The Prescription Drug User Fee Act target action date for narsoplimab has been set as July 17, 2021.
Narsoplimab is an IgG-4 monoclonal antibody that inhibits the effector enzyme MASP-2 of the lectin pathway. In addition to Priority Review, the agent was previously granted breakthrough therapy designations and orphan drug designations by the FDA for the treatment of HSCT-TMA, as well as IgA nephropathy.
"The filing of our BLA by FDA marks an important milestone on the path to commercialization of narsoplimab," stated Gregory A. Demopulos, MD, chairman, and chief executive officer of the Omeros Corporation. "There is no FDA-approved product for the treatment of transplant-associated TMA, a frequently fatal complication of stem cell transplantation. We appreciate FDA’s collaborative approach throughout the development of our breakthrough therapy-designated product narsoplimab, and we are committed to continue working closely with the FDA review team to make the drug available to patients who need it."
Promising results were reported on narsoplimab last year during the 23rd Congress of the European Hematology Association. The agent was studied in a 3-stage, uncontrolled, multiple dose-escalation phase 2 study in which it demonstrated an improvement in overall survival (OS) as compared with historical controls. Narsoplimab also displayed an acceptable safety profile with the most frequently reported adverse events being consistent with those observed with historical controls.2
Thestatistically significant improvement in median OS among patients who received narsoplimab in the study was 347.0 days versus 21.0 days for patients who received a control agent in a historical analysis (P <.0001). In addition, patients treated with narsoplimab had a100-day survival rate of 68%, with 83% of those who received treatment for ≥4 weeks still alive at 100 days. Results also show that 93% of patients who responded to treatment survived to the 100-day mark.
Treatment with narsoplimab also demonstrated statistically significant and clinically meaningful mean changes in platelet counts from baseline, meeting the primary end point of the trial. Statistically significant and clinically meaningful changes in lactate dehydrogenase levels and haptoglobin levels compared to the levels observed at baseline were also observed. There was no significant change in the mean creatinine levels though.
In terms of safety, narsoplimab was well-tolerated overall. Adverse events (AEs) occurred in ≥ 20 of patients of which the most common were diarrhea (33%), and nausea (22%). The other AEs observed included fatigue, hypokalemia, neutropenia, and vomiting, which occurred in 22% of patients, each. At least 2 patients experienced serious AEs including the development of graft-versus-host-disease, neutropenic sepsis, and acute renal failure.
The phase 2 study of narsoplimab followed a 3-cohort design with patients in stage 1 of the study receiving ascending-dose. Overall, patients received narsoplimab at low-, median-, or high-dose levels. In, stage 2 of the study, narsoplimab was administered in 4 once-weekly doses a the high-dose level. Four additional weekly doses were allowed in sage 3 for any patients who tolerated the agent well in stages 1 and 2.
Patients with persistent HSCT-TMA were eligible to enroll given they had onset of the condition within 30 days after transplant of 2 weeks following modification of treatment with a calcineurin inhibitor.
1. Biologics License Application for narsoplimab in HSCT-TMA accepted for priority review by U.S. FDA. News release. Omeros Corporation. January 19, 2021. Accessed January 19, 2021. https://bit.ly/38VhtV8
2. Rambaldi A, Khaled S, Smith M, et al. Improved survival following OMS721 treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (HCT-TMA). Presented at: 23rd Congress of European Hematology Association; June 14-17, 2018; Stockholm, Sweden.