In late October, commercial-stage biopharmaceutical company Omeros Corporation (“Omeros”) announced the publication of data from its narsoplimab clinical trial. During the trial, researchers evaluated the therapy as a treatment for hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA). Often, HSCT-TMA occurs following stem cell transplants. However, while the condition is often fatal, there are no approved treatments. Omeros is looking to change that, particularly considering the new data.
In developing narsoplimab, Omeros hoped to meet an unmet treatment need. Narsoplimab is a MASP-2 inhibitor that received Breakthrough Therapy designation from the FDA. According to the FDA, Breakthrough Therapy designation:
is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).
Currently, Omeros also submitted a Biologics License Application for HSCT-TMA. During the clinical trial, patients received intravenous narsoplimab every week for up to 2 months. Many patients had other comorbidities including organ failure or dysfunction, and infections. Primary endpoint was organ function improvement, no more need for transfusions, or platelet and LDH improvement. Secondary endpoints looked at survival rate and changes in platelets, hemoglobin, haptoglobin, LDH, and creatinine.
Ultimately, narsoplimab was safe, effective, and well-tolerated for patients with HSCT-TMA. Narsoplimab significantly improved survival rate and organ function. While generally well-tolerated, there were some side effects, including nausea and diarrhea, low white blood cell count, vomiting, and fever. Additionally, six patients died during the course of the study. However, these were attributed to their conditions rather than narsoplimab treatment.
In an article published in Clinical Advances in Hematology & Oncology, researchers describe HSCT-TMA as:
inflammatory and thrombotic diseases of the microvasculature characterized by hemolytic anemia, thrombocytopenia, and evidence of organ damage, particularly acute renal failure. This syndrome occurs in 10% to 20% of patients with allogeneic hematopoietic stem cell transplants (HSCTs).
Typically, thrombotic microangiopathies refer to either atypical hemolytic-uremic syndrome (aHUS) or thrombotic thrombocytopenic purpura. However, HSCT-TMA may occur outside of this realm. Another article from Bone Marrow Transplantation explains:
The incidence of TA-TMA varies widely, in part, due to the lack of standard diagnostic criteria. The reported incidence of TA-TMA following allogeneic transplant ranged from 0% to 64% with mortality as high as 100% of cases in a review of 35 published case series, though 28 different diagnostic criteria were used.
Symptoms and clinical features may include:
- Organ failure