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Jump to Key Points The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has confirmed its recommendation to refuse marketing authorization for narsoplimab (Yartemlea, Omeros Ireland Limited) for hematopoietic stem cell transplant (HSCT)-associated thrombotic microangiopathy (TA-TMA). The opinion, adopted on October 15, 2026, follows a re-examination requested by the company after the committee’s initial negative opinion on June 25, 2026.
The monoclonal antibody was intended for adults and children aged 2 years or older with high-risk TA-TMA.
Mechanism of Action
TA-TMA is a serious and potentially life-threatening complication of HSCT. Conditioning regimens and immunosuppressive treatments given around the time of transplant can damage small blood vessels via complement activation, leading to microvascular clots and organ injury.
Narsoplimab targets mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of complement. By blocking MASP-2, the drug was expected to reduce endothelial injury and thrombus formation. It is given by intravenous infusion. Yartemlea received orphan designation in the EU in November 2018 for use in HSCT.
- CHMP reaffirmed refusal of narsoplimab EU authorization for HSCT-associated TA-TMA.
- Single-arm adult study (n=28) lacked comparator; efficacy not established.
- Concomitant therapies + protocol changes confounded platelet, LDH, organ-response outcomes.
- Pediatric data insufficient for dose, efficacy, or safety; adult benefit not extrapolatable.
- EU compassionate-use program ending; current patients to complete treatment courses.
Evidence Under Scrutiny
The application was based on a single-arm study of 28 adults with TA-TMA after HSCT who received narsoplimab. The primary measures were changes in platelet count and lactate dehydrogenase levels. Investigators also assessed organ function, including kidney and lung function, and the need for transfusions.
The company also submitted data from an expanded-access program involving 27 adults and 16 children. In addition, it compared survival among treated patients with that of similar untreated patients outside the studies.
The CHMP concluded that evidence was insufficient to establish efficacy. Because the main study had no placebo or active comparator and participants received other medications alongside narsoplimab, the committee said it was not possible to determine whether observed improvements were due to the drug, concomitant therapies, or other factors. It also raised concerns about the conduct of the study, including changes made while it was ongoing, how effectiveness was measured, and how the dose was selected.
The agency further noted that published literature suggested other TA-TMA treatments produced similar results, and that the external survival comparison could not reliably confirm a treatment effect. In children, data were too limited to support the proposed dose or to assess efficacy and safety. Because benefit was not demonstrated in adults, the results could not be extrapolated to younger patients. The committee added that the study results also did not confirm the proposed mechanism of action in this condition.
Re-examination and Conditional Approval Option
During the re-examination, the CHMP reassessed the data submitted by the company, consulted a group of experts in HSCT and its complications, and considered input from other healthcare professionals who contacted the agency. It concluded that the concerns raised in the initial assessment remained unresolved.
The company also considered switching to a conditional marketing authorization, a pathway intended for medicines addressing unmet need on the basis of less comprehensive data. The EMA said the application did not meet the criteria because the benefits of the medicine had not been demonstrated.
Impact on Patients and Next Steps
Due to rising demand in the US market (the FDA approved Yartemlea in December 2025), Omeros has informed the EMA that it intends to end the EU compassionate-use program. Patients currently receiving narsoplimab will be supplied with enough medicine to complete their treatment courses. The EMA advised patients in clinical trials or compassionate-use programs to speak with their doctors about their treatment. The company is also assessing the status of ongoing clinical trials required for authorization in the EU.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
