Omeros announced agreement with the FDA on the response-based primary endpoint for its pivotal trial to support the biologics license application (BLA) for narsoplimab to treat hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), according to a company news release.
Narsoplimab, also known as “OMS721,” is Omeros’ lead human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2). There is no approved product for the treatment or prevention of HSCT-TMA, and narsoplimab is the only drug in development for the treatment of HSCT-TMA to be granted FDA’s breakthrough therapy designation.
As previously reported, FDA had already agreed to the majority of the criteria proposed for the response-based primary endpoint, and today’s announced agreement with FDA has finalized the remaining components of the endpoint. The response-based primary endpoint for HSCT-TMA requires a showing of both a beneficial effect on the underlying HSCT-TMA disease process and a meaningful improvement in patients’ clinical status. The endpoint includes laboratory measures and markers of organ function as well as platelet and red blood cell transfusion burden.
Based on a review of the available data from the open-label, single-arm, pivotal trial, Omeros is confident that the study will meet the primary endpoint.
With finalization of the primary endpoint, the next steps for the planned commercialization of narsoplimab for HSCT-TMA are to:
- Complete the ongoing data collection from medical records of patients already treated with narsoplimab in the clinical trial or under compassionate use. This will enable preparation of complete patient narratives for inclusion in the clinical sections of the BLA and of the marketing authorization application (MAA), which is being prepared for submission to the European Medicines Agency (EMA). No additional patients are needed for submission of the BLA to support approval of narsoplimab in this indication.
- Meet with the program’s EMA rapporteurs, scheduled to begin this summer, to refine further the path to European approval. Omeros intends to harmonize the contents of the MAA and BLA.
- Complete and submit the BLA and MAA. FDA has previously confirmed that Omeros may submit this BLA on a rolling basis, and the company is finalizing for review by FDA its proposed schedule of module submissions under that rolling BLA. As also previously reported, the nonclinical sections of the BLA have been written and are expected to comprise the first module of the BLA submission. EMA does not have a similar rolling submission process.
“Through continued collaboration with FDA, we’ve now reached agreement on the full set of criteria for the primary endpoint for our narsoplimab pivotal trial in patients with stem cell transplant-associated TMA,” Gregory A. Demopulos, MD, chairman and chief executive officer of Omeros, said in a company news release. “Based on review of the available data, we’re confident in both the magnitude and rate of response – as defined by the agreed criteria – that we’re seeing with narsoplimab in these patients. The path has now been cleared for us to complete and submit the BLA, and we look forward to making narsoplimab available as quickly as possible to patients who need it.”
Hematopoietic stem cell transplant-associated TMA is a significant, costly and often lethal complication of stem cell transplants. This condition is a systemic, multifactorial disorder caused by endothelial cell damage induced by infection, graft-versus-host disease, and therapies used as part of stem cell transplantation. In addition to TMA, veno-occlusive disease, diffuse alveolar hemorrhage and a range of other disorders are associated with endothelial cell damage. Collectively, these disorders comprise the endothelial injury syndrome. The lectin pathway of complement is activated by endothelial damage, and narsoplimab specifically targets MASP-2, the effector enzyme of the lectin pathway.