FDA Approves Narsoplimab (Yartemlea) As First TA-TMA Therapy

The US Food and Drug Administration has approved Omeros Corporation’s narsoplimab-wuug (Yartemlea) for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA).1

According to a December 24, 2025, release from the Company, the decision makes narsoplimab the first and only approved lectin pathway inhibitor and is approved for use in adults and in children ≥ 2 years of age.1

“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, said in a statement.1 “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-versus-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.”

Narsoplimab is a fully human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), a novel pro-inflammatory protein target and the effector enzyme of the lectin pathway of complement. Inhibition of MASP-2 has been demonstrated to leave intact the antibody-dependent classical complement activation pathway, a critical component of the acquired immune response to infection.1

Omeros’ first Biologics License Application for narsoplimab was met with a Complete Response Letter in which the FDA expressed difficulty in estimating the treatment effect of narsoplimab in HSCT-TMA and asserted that additional information would be needed to support regulatory approval.1,2

The Company later filed a Class 2 resubmission with the Agency with data from a primary set of analyses comparing overall survival for narsoplimab-treated patients to overall survival for an external control group of TA-TMA patients showing clinically meaningful and statistically significant improvements in survival associated with narsoplimab treatment. Also included in the resubmission were data describing survival in Omeros’ expanded access program in which adult and pediatric TA-TMA patients were treated with narsoplimab.2,3

Its December 24, 2025, approval was based on results from a single-arm, open-label study in adults with TA-TMA (the TA-TMA Study; n = 28), supported by additional data from an expanded access program (EAP; n = 221 adult and pediatric patients). In the EAP, 19 patients (13 adult and 6 pediatric) had evaluable patient-level response data.1

Efficacy was assessed by TMA complete response (CR), defined as improvement in key laboratory markers of TMA (platelet counts and LDH levels) together with either improved organ function or transfusion independence. CR was achieved in 17 out of 28 patients (61%) in the TA-TMA Study and 13 out of 19 evaluable EAP patients (68%). Across the TA-TMA Study and the EAP, 100-day survival from the time of TMA diagnosis (based on all-cause mortality) was 73% (95% confidence interval [CI], 52-86) and 74% (95% CI, 48-88), respectively. All patients met international harmonization criteria for high-risk TA-TMA, classifying each patient as having a poor prognosis and high risk of death.1

In peer-reviewed publications, treatment with narsoplimab was associated with a 3- to 4- fold reduced risk of mortality compared with an external control cohort.1 In the EAP, narsoplimab was used both as first-line therapy and in high-risk TA-TMA patients who had failed or discontinued one or more prior regimens, namely off-label complement inhibitors and/or defibrotide. In these previously refractory high-risk patients, narsoplimab was associated with 50% 1-year survival, compared with historical 1-year survival rates reported as < 20%.1

As described in the release, all patients in the TA-TMA Study had multiple risk factors for poor outcomes, and adverse reactions were reported regardless of causality or relatedness to narsoplimab. The most common adverse reactions (≥20%) were viral infections, sepsis, hemorrhage, diarrhea, vomiting, nausea, neutropenia, pyrexia, fatigue, and hypokalemia.1

Serious adverse reactions occurred in 61% of narsoplimab-treated patients; those reported in >5% included acute kidney injury, confusional state, acute respiratory failure, neutropenic sepsis, septic shock, pulmonary edema, and vomiting. Fatal adverse reactions were reported in 7% of patients, including neutropenic sepsis and septic shock. No new clinically significant safety signals were identified in patients treated with narsoplimab in the EAP.1

Of note, narsoplimab has no Boxed Warning and no Risk Evaluation and Mitigation Strategy (REMS), and vaccinations are not required prior to treatment.1

“Just as in adults, [narsoplimab]’s indication to treat TA-TMA in children two years of age and older is tremendously important,” said Michelle Schoettler, MD, assistant professor of Pediatric Oncology and Hematopoietic Cellular Therapy at Emory University.1 “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. 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… My clinical experience with narsoplimab through the expanded access program, 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. Omeros Corporation. FDA Approves Omeros’ YARTEMLEA® – First and Only Therapy Indicated for TA-TMA. December 24, 2025. Accessed December 24, 2025. https://investor.omeros.com/news-releases/news-release-details/fda-approves-omeros-yartemlear-first-and-only-therapy-indicated

2. Omeros Corporation. Omeros Receives Complete Response Letter from FDA for Biologics License Application for Narsoplimab in the Treatment of HSCT-TMA. October 18, 2021. Accessed December 19, 2025. https://investor.omeros.com/news-releases/news-release-details/omeros-receives-complete-response-letter-fda-biologics-license

3. Omeros Corporation. FDA Accepts Resubmission of BLA for Narsoplimab for Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (TA-TMA) and Assigns Late September PDUFA Date. May 6, 2025. Accessed December 19, 2025. https://investor.omeros.com/news-releases/news-release-details/fda-accepts-resubmission-bla-narsoplimab-hematopoietic-stem-cell