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The FDA issued a complete response letter to the company responsible for developing narsoplimab because of the inability to estimate treatment effects on patients receiving hematopoietic stem cell transplant–associated thrombotic microangiopathy.
The FDA issued a complete response letter in response to a Biologics License Application for the drug candidate narsoplimab (OMS721) as treatment for patients with hematopoietic stem cell transplant–associated thrombotic microangiopathy (HSCT-TMA), according to a press release from the agent’s developer Omeros.1
The FDA cited not being able to estimate the effect of narsoplimab on HSCT-TMA and indicated they would need more information to support an approval. Within the complete response letter, the FDA did not raise concerns over the chemistry, manufacturing and controls, or CMC; safety; or nonclinical issues.
Going forward, Omeros plans to request a Type A meeting to discuss the letter with the FDA and determine the quickest path towards approval.
Narsoplimab targets mannan-binding lectin–associated serine protease-2 (MASP-2), which is the effector enzyme of the lectin pathway. The therapy’s safety and efficacy was examined in a phase 2 trial (NCT02222545) in patients with HSCT-TMA, the results of which were presented at the 2020 European Hematology Association Congress.2
This trial enrolled 28 patients, 71% of whom were male with a mean age of 48 years. Moreover, 96% of patients had underlying malignant disease and 93% were reported to have multiple risk factors such as graft-versus-host disease (64%), infection (79%), noninfectious pulmonary complications (18%), and neurological signs (36%) prior to developing HSCT-TMA and throughout the trial.
From baseline, investigators observed statistical (P <.01) and clinical improvements in platelet count, lactate dehydrogenase, and haptoglobin. The entire patient population had an overall response rate (ORR) of 54% and those who were treated for 4 weeks or more (n = 23) had an ORR of 65%. Overall, patients who received treatment achieved a 100-day survival rate of 68% (n = 19) whereas the rate in those treated for 4 weeks or longer was 83%. In responders, the 100-day rate of survival achieved was 93%.
The FDA-agreed primary end point of the trial was novel response based on composite measures requiring laboratory TMA markers and clinical status. The secondary end points were survival and changes in TMA laboratory markers.
The most common adverse effects (AEs) following treatment with narsoplimab were nausea, vomiting, diarrhea, hypokalemia, neutropenia, and fever. Investigators reported that 6 deaths occurred due to sepsis, acute myeloid leukemia progression, and graft-versus-host disease. No infusion AEs were reported.
Narsoplimab has previously received a breakthrough therapy designation and orphan drug designation for both HSCT-TMA and IgA nephropathy.
1. Omeros Received Complete Response Letter from FDA for Biologics License Application For Narsoplimab in the Treatment of HSCT-TMA. News Release. Omeros Corporation. October 18, 2021. Accessed October 20, 2021. https://bwnews.pr/3jjRFH2
2. Rambaldi A, Smith M, Whitaker S, Khaled S. Narsoplimab (OMS721) for the treatment of adult hematopoietic stem cell transplant-associated thrombotic microangiopathy. Presented at the 2020 European Hematology Association Congress; June 11-21, 2020; Virtual. Accessed October 13, 2021. Abstract S262. https://bit.ly/3vsZrDl