FDA Approves Narsoplimab for Hematopoietic Stem Cell Transplant–Associated Thrombotic Microangiopathy

The FDA has approved narsoplimab-wuug (Yartemlea) injection for the treatment of adults and children aged 2 years and older with hematopoietic stem cell transplant–associated thrombotic microangiopathy (TA-TMA).¹

The efficacy of the lectin pathway inhibitor was evaluated in 28 patients enrolled in the single-arm, open-label TA-TMA Study. Data from an additional 19 evaluable patients enrolled in an expanded access program (EAP) also supported the regulatory decision.

Findings from the TA-TMA Study indicated that narsoplimab elicited a TMA complete response (CR) rate of 61% (95% CI, 40.6%-78.5%) in evaluable adult patients (n = 28); this rate was 68% in the evaluable EAP patients. When broken down further, the TMA response rate was 67% (95% CI, 22.3%-95.7%) in pediatric patients (n = 6) and 69% (95% CI, 38.6%-90.9%) in adult patients (n = 13) in the EAP.²

Additional data from the TA-TMA study showed that 61% and 75% of patients experienced improvements in TMA markers like platelet count and lactate dehydrogenase (LDH) levels, respectively. In the EAP pediatric patients, these rates were 67% and 83%; in the EAP adult patients, these rates were 69% and 85%. Moreover, 74% of patients in the TA-TMA study experienced improved organ function, and 48% achieved freedom from red blood cell or platelet transfusion. In the EAP pediatric patients, these rates were 83% and 60%, respectively, and in the EAP adult patients, these respective rates were 85% and 69%.

Additionally, the 100-day survival time from TMA diagnosis was 73.4% (95% CI, 52.2%-86.4%); this rate was 73.7% (95% CI, 47.9%-88.1%) in the EAP cohort.

“This approval is a long-awaited breakthrough in hematopoietic cell transplantation and TA-TMA care,” Miguel-Angel Perales, MD, chief of the Adult Bone Marrow Transplantation Service at Memorial Sloan Kettering Cancer Center, stated in a news release.³ “Until now, we’ve lacked an effective TA-TMA therapy and relied largely on supportive measures such as modifying calcineurin inhibitors, which can significantly increase the risk of life-threatening graft-vs-host disease. Based on a compelling data package, narsoplimab delivers robust response rates and improved survival in TA-TMA, with a favorable benefit-risk profile and a safety profile consistent with that seen in patients undergoing hematopoietic stem cell transplantation. As the first and only drug approved for TA-TMA, narsoplimab is a practice-changing advance for patients facing this devastating complication.”

How was narsoplimab examined in the TA-TMA Study and the EAP cohort?

The TA-TMA Study enrolled patients with a confirmed diagnosis of TA-TMA by the following diagnostic criteria:

• A platelet count of less than 150,000/µL,
• Evidence of microangiopathic hemolysis, which could have included the presence of schistocytes, serum LDH above the upper limit of normal (ULN) and/or haptoglobin less than the lower limit of normal; and
• Renal dysfunction.

Those in the EAP were similarly thrombocytopenic and also showcased evidence of microangiopathic hemolytic anemia.

In the former study, patients received narsoplimab at 4 mg/kg (n = 24) or 370 mg (n =4) once weekly. Across both cohorts, the median number of administrations of narsoplimab was 8 (range, 2-34). The median duration of treatment was 8 weeks (range, 2-16).

The primary efficacy assessment of narsoplimab was based on TMA response, which was defined as improvement in both of the laboratory TMA markers LDH and platelet counts, and either improvement in organ function or independence from transfusions. The same criteria were applied to both patient cohorts.

Improvement in platelet count was defined as follows:

• For baseline platelet count of up to 20,000/μL, at least a three-fold increase in platelet count, postbaseline platelet count of greater than 30,000/μL, and no platelet transfusions within 2 days before the platelet count assessment.
• For baseline platelet count of greater than 20,000/μL, at least a 50% increase in platelet count, platelet count of greater than 75,000/μL, and no platelet transfusions within 2 days prior to the platelet count assessment.

What were the characteristics of the patients included in the analyses?

In the TA-TMA study, the median patient age was 48 years (range, 22-68). More than half of patients were White (61%), not Hispanic or Latino (93%), male (71%), had elevated LDH of at least two times the ULN (71%), and grade II to IV acute graft-vs-host disease (GVHD; 68%). Moreover, 96%, 75%, 18% and 57% of patients had organ, renal, pulmonary, or neurological dysfunction, respectively. Moreover, the majority of patients had infections (86%).

In the EAP pediatric cohort, the median patient age was 10.5 years (range, 5-15). Most patients were female (67%) and had grade II to IV acute GVHD (83%); all had elevated LDH at least two times the ULN. Additionally, all patients had organ dysfunction, 83% had renal dysfunction, and about one-third (33%) had neurological dysfunction. All pediatric patients had infections.

In the EAP adult cohort, the median age was 62 years (range, 19-71). More than half of patients were female (62%), about half had elevated LDH (54%), and most had grade II to IV acute GVHD (85%). All adult patients had organ and renal dysfunction; 15% had pulmonary dysfunction, and 31% had neurological dysfunction. Sixty-two percent of patients had infections.

What was learned about the safety profile of narsoplimab?

Serious toxicities were reported in 61% of patients who received narsoplimab in the TA-TMA Study. Moreover, adverse effects (AEs) led to dose interruptions for 7% of patients.

The most common AEs experienced by at least 15% of patients in the study were hemorrhage (all grade, 43%; grade ≥ 3, 7%), diarrhea (36%; 7%), viral infection (36%; 7%), neutropenia (36%; 36%), pyrexia (36%; 4%), vomiting (32%; 7%), fatigue (29%; 4%), hypokalemia (25%; 11%), nausea (25%; 4%), sepsis (25%; 21%), pneumonia (18%; 14%), hypotension (18%; 11%), abdominal pain (18%; 4%), anemia (18%; 11%), and back pain (18%; 0%).

An additional 221 patients with TA-TMA were treated with narsoplimab as part of the EAP, and no new clinically significant safety signals were observed.

What was the road that led to the approval of narsoplimab as the first and only therapy indicated for TA-TMA?

In October 2021, Omeros Corporation, the drug developer, announced that they received a complete response letter from the FDA for its biologics license application (BLA) seeking approval of narsoplimab for use in TA-TMA.⁴ In the letter, the regulatory agency expressed difficulty in estimating the treatment effect of the drug in TA-TMA and requested additional information to support approval. No chemistry, manufacturing, and controls (CMC), safety, or nonclinical issues were raised in the letter. In May 2025, the BLA for narsoplimab was resubmitted.⁵

What is the significance of the narsoplimab approval?

“Just as in adults, [narsoplimab's] indication to treat TA-TMA in children 2 years of age and older is tremendously important. Peer-reviewed clinical publications in TA-TMA have steadily advanced our understanding of the disease in children – its biology, diagnostic criteria, and increasing recognition – and have revealed the limitations and risks of relying on off-label options in this setting," Michelle Schoettler, MD, assistant professor of Pediatric Oncology and Hematopoietic Cellular Therapy at Emory University, stated in a news release.³ "Across the published pediatric experience, [narsoplimab] has produced strong and consistent benefit, including in very high-risk children with organ dysfunction and in those who have failed prior complement-inhibition therapy."

She added: "When used first-line, [narsoplimab' has been associated with approximately 75 percent one-year survival; and even in children refractory to one or more off-label complement inhibitors, one-year survival is approximately triple historical rates that have remained below 20 percent. My clinical experience with [narsoplimab] through the [EAP], including in very young patients, has reinforced that it needs to be readily available for children when TA-TMA emerges. With this approval, effective TA-TMA therapy can become the pediatric standard instead of the exception – and that will save children’s lives.”

References

1. FDA approves first drug to treat serious complication of stem cell transplant. FDA. December 24, 2025. Accessed December 30, 2025.
2. Yartemlea. Prescribing information. Omeros Corporation; 2025. Accessed December 30, 2025. https://pi.omeros.com/us/yartemlea-uspi.pdf
3. FDA approves Omeros' YARTEMLEA — the first and only therapy indicated for TA-TMA. News release. Omeros Corporation. December 24, 2025. Accessed December 30, 2025. https://www.businesswire.com/news/home/20251224065139/en/FDA-Approves-Omeros-YARTEMLEA-First-and-Only-Therapy-Indicated-for-TA-TMA
4. Omeros receives 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 December 30, 2025. https://investor.omeros.com/news-releases/news-release-details/omeros-receives-complete-response-letter-fda-biologics-license
5. FDA accepts resubmission of BLA for narsoplimab for hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) and assigns late September PDUFA date. News release. Omeros Corporation. May 6, 2025. Accessed December 30, 2025. https://investor.omeros.com/news-releases/news-release-details/fda-accepts-resubmission-bla-narsoplimab-hematopoietic-stem-cell