Narsoplimab-wuug (Yartemlea)
Number: 1099
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses narsoplimab-wuug (Yartemlea) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.
Note: Requires Precertification:
Precertification of narsoplimab-wuug (Yartemlea) is required of all Aetna participating providers and members in applicable plan designs. For precertification of narsoplimab-wuug (Yartemlea), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification.
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Criteria for Initial Approval
Aetna considers narsoplimab-wuug (Yartemlea) medically necessary for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) when all of the following criteria are met:
- The member is 2 years of age or older; and
- Diagnosis has been confirmed by both of the following:
- Platelet count less than 150,000/µL; and
- Evidence of microangiopathic hemolysis (presence of schistocytes, serum lactate dehydrogenase [LDH] greater than the upper limit of normal [ULN] and/or haptoglobin less than the lower limit of normal [LLN]); and
- The member has an ADAMTS13 activity level greater than or equal to 10%; and
- The requested medication will not be used in combination with another complement inhibitor (e.g., Soliris, Ultomiris) or defibrotide (Defitelio).
Aetna considers all other indications as experimental, investigational, or unproven.
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Continuation of Therapy
Aetna considers continuation of narsoplimab-wuug (Yartemlea) therapy medically necessary for treatment in members requesting reauthorization for an indication listed in the Criteria for Initial Approval section when there is no unacceptable toxicity while on the current regimen, the member demonstrates a positive response to therapy (e.g., improvement in platelet levels and renal function, normalization of LDH and haptoglobin levels), and the requested medication will not be used in combination with another complement inhibitor (e.g., Soliris, Ultomiris) or defibrotide (Defitelio).
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Related Policies
Dosage and Administration
Yartemlea is available in 2-mL single-dose glass vials containing 370 mg of narsoplimab-wuug (185 mg/mL) for intravenous use in persons 2 years of age and older with hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA).
The recommended dosage and administration for Yartemlea include:
- Persons greater than or equal to 50 kg: 370 mg given as an intravenous infusion over 30 minutes once weekly. Frequency is increased to twice weekly if there is inadequate improvement in TA-TMA signs and symptoms; or
- Persons less than 50 kg: 4 mg/kg given as an intravenous infusion over 30 minutes once weekly. Frequency is increased to twice weekly if there is inadequate improvement in TA-TMA signs and symptoms.
Source: Omeros Corporation, 2025
Background
U.S. Food and Drug Administration (FDA)-Approved Indications
- Yartemlea is indicated for the treatment of adult and pediatric patients 2 years of age and older with hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA).
Narsoplimab-wuug, branded as Yartemlea (Omeros Corporation), is a monoclonal antibody that specifically inhibits MASP-2, the effector enzyme of the lectin complement pathway. This inhibition blocks the lectin-dependent activation of complement components C3 and C4 while leaving the classical and alternative complement pathways unaffected. In the context of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA), the inhibition of MASP-2 is believed to prevent cellular damage mediated by the lectin pathway, particularly protecting endothelial cells in small blood vessels from injury.
Although there are no labeled contraindications for Yartemlea, there is a risk for serious infections. Patients treated with Yartemlea have experienced serious and potentially life-threatening infections. In clinical trials, 36% (10 out of 28) of patients with TA-TMA receiving Yartemlea reported serious infections, regardless of causality. These infections included sepsis, viral infections, pneumonia, bacteremia, fungal infections, gastroenteritis, respiratory tract infections, and urosepsis. If Yartemlea is given to patients with active infections, it is essential to closely monitor them for any signs and symptoms of worsening infection and to provide prompt treatment as needed.
The most common adverse reactions (incidence of 20% or more and independent of causality) include viral infections, sepsis, hemorrhage, diarrhea, vomiting, nausea, neutropenia, pyrexia, fatigue and hypokalemia.
Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (TA-TMA)
Hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), also called transplant-associated TMA (TA-TMA), is a serious and potentially life-threatening complication of hematopoietic stem cell transplant (HSCT), typically developing 20 to 100 days after transplantation. The condition is characterized by microvascular endothelial injury leading to microangiopathic hemolytic anemia (MAHA) with persistent schistocytosis, elevated markers of hemolysis, thrombocytopenia, and microvascular thrombosis leading to ischemic tissue damage, causing multi-organ dysfunction, most commonly involving the kidneys. Activation of the lectin pathway of complement may play a central role in disease pathogenesis. Narsoplimab, a human monoclonal antibody that targets Mannan-binding lectin-associated serine protease-2 (MASP-2), serves as a potent inhibitor of this lectin pathway (FDA, 2025;Li and Sartain, 2024; Pandrowala et al., 2023).
Khaled et al. (2022) report that hematopoietic stem-cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a serious complication with high mortality rates and no approved treatments. HSCT-TMA arises from endothelial injury that activates the lectin pathway of complement. The authors evaluated the safety and efficacy of narsoplimab (OMS721), an inhibitor of mannan-binding lectin-associated serine protease-2 (MASP-2), in adults with HSCT-TMA. In this single-arm open-label pivotal trial (NCT02222545), patients received intravenous narsoplimab weekly for 4 to 8 weeks. The primary endpoint (response rate) required clinical improvement in two areas—laboratory TMA markers (including platelet count and lactate dehydrogenase) and organ function or freedom from transfusion. A total of 28 patients who received at least one dose were included in the full analysis set (FAS). The response rate was 61% in this population, with similar outcomes across various patient subgroups based on baseline characteristics, HSCT details, and complications. Organ function improved in 74% of patients, and the 100-day survival rate after HSCT-TMA diagnosis was 68% for the FAS population and 94% for responders, with a median overall survival of 274 days in the FAS group. Narsoplimab was well tolerated, with adverse events consistent with the patient population and no significant safety concerns. The authors concluded that narsoplimab treatment is safe, significantly improves laboratory TMA markers, and leads to clinical responses and favorable overall survival.
Schoettler et al. (2025) emphasize that inappropriate complement activation is a significant factor in hematopoietic cell transplant-associated thrombotic microangiopathy (TA-TMA). In a Phase 2 clinical trial, treatment with narsoplimab, an inhibitor of MASP-2, the key enzyme in the lectin pathway, achieved a response rate of 61% in adults with TA-TMA. Following these encouraging results, a global expanded access program (EAP) was initiated to allow compassionate use of the treatment. The authors report the survival outcomes of 136 participants, including children under 16 years and adults aged 16 and older, enrolled in the EAP from October 2017 to October 2023. Among the 50 children, most underwent allogeneic hematopoietic cell transplantation (HCT) (n=44), with 37 classified as high-risk (HR) and 30 (81.1%) exhibiting organ dysfunction at the time of TA-TMA diagnosis. The one-year overall survival (OS) for pediatric allogeneic recipients with HR TA-TMA who received narsoplimab as first-line therapy (n = 12) was 75.0%, compared to 56.2% for those treated as second-line (n = 25, including 20 refractory to eculizumab). Among the six children with solid tumors who underwent autologous HCT, the one-year OS was 80%. In the adult cohort of 86, 84 received allogeneic HCT, with 65 having HR TA-TMA, and 57 (87.7%) presenting with organ dysfunction at diagnosis. The one-year OS for adults with HR TA-TMA receiving narsoplimab as first-line therapy (n = 49) was 58.0%, while it was 40.5% for those receiving it as second-line therapy (n = 16). No significant safety concerns were noted. The authors concluded that this real-world study, which included patients with severe TA-TMA, demonstrated excellent survival rates in both children and adults, supporting the use of narsoplimab.
In an UpToDate review on the "Diagnostic approach to suspected TTP, HUS, or other thrombotic microangiopathy (TMA)", Chaturveti (2025) state that recent hematopoietic stem cell transplantation (autologous or allogeneic) should prompt consideration of transplantation-associated TMA. The author emphasizes that the initial evaluation of a patient with TMA syndrome should focus on distinguishing thrombotic thrombocytopenic purpura (TTP) and complement-mediated TMA (CM-TMA), both of which require specific treatments (urgent for TTP), from other TMAs or systemic disorders that may present with microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. MAHA is defined as hemolytic anemia caused by the fragmentation of red blood cells (RBCs) in the bloodstream, resulting in schistocytes on a peripheral blood smear. TMA is characterized by pathological lesions in arterioles and capillaries leading to microvascular thrombosis, typically identified through complete blood count (CBC) results and blood smear analysis rather than biopsy. Although not all MAHA cases are attributed to TMA, nearly all TMAs lead to MAHA and thrombocytopenia. The evaluation process aims to confirm MAHA and thrombocytopenia while excluding systemic disorders that could produce similar findings. Key tests include a CBC with platelet count, blood smear review by an experienced clinician, lactate dehydrogenase (LDH), bilirubin, creatinine, coagulation tests, liver function tests, troponin, and an electrocardiogram. Evaluating the likelihood of TTP is essential, as urgent therapeutic plasma exchange (TPE) requires considerable resources. TTP often presents with nonspecific symptoms, preserved kidney function, and varying neurological signs. The PLASMIC score is utilized to estimate the probability of ADAMTS13 activity ≤10, which is characteristic of TTP. For most patients exhibiting MAHA, thrombocytopenia, and a PLASMIC score of ≥5 without an alternative explanation, a presumptive diagnosis of TTP is made, prompting the immediate decision to initiate therapeutic plasma exchange.
Matsui et al. (2026) report that hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) is a potentially fatal multisystem complication of hematopoietic cell transplantation, for which no approved treatment currently exists. In a single-arm study (NCT02222545), treatment with narsoplimab for TA-TMA showed a median overall survival (OS) of 274 days from the date of diagnosis. This study compares the OS observed in two cohorts treated with narsoplimab to that of a well-matched external control group to assess the survival benefit in patients with high-risk TA-TMA. Specifically, OS in patients aged 16 years and older with high-risk TA-TMA treated with narsoplimab in the single-arm study or the narsoplimab expanded access program (EAP; NCT04247906) was compared to OS in a control group from the Kyoto Stem Cell Transplantation Group (KSCTG) registry. Narsoplimab-treated patients in the single-arm study (N = 28) experienced a fourfold reduction in mortality risk compared to patients from the KSCTG registry (N = 111; hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.19, 0.34; P < .0001). Similarly, high-risk patients treated with narsoplimab in the EAP (N = 49) had a significantly lower mortality risk than those from the KSCTG registry (N = 121; HR 0.38; 95% CI 0.28, 0.51; P < .0001). When combining narsoplimab-treated patients from both the single-arm study and the EAP (N = 77) and comparing them to KSCTG patients, the HR for mortality was 0.28 (95% CI, 0.22, 0.37; P < .0001). In conclusion, narsoplimab treatment significantly reduced mortality in patients with high-risk TA-TMA compared to a well-matched external control group that did not receive the treatment, supporting narsoplimab as a potential therapeutic option for this condition.
On January 5, 2026, the U.S. FDA approved Yartemlea injection for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) in patients aged 2 years and older. This approval was based on the TA-TMA Study, a single-arm, open-label trial that included two cohorts of patients treated with narsoplimab: one from the pivotal clinical trial OMS721-TMA-001 (NCT02222545) and the other from an expanded access program (EAP) (NCT04247906). The TA-TMA cohort comprised 28 adults, with a median time from hematopoietic stem cell transplantation (HSCT) to TMA diagnosis of 73.5 days (range: 21-436 days) and a median time from TMA diagnosis to the first dose of narsoplimab of 13.5 days (range: 4-196 days). The EAP included 19 patients, consisting of 6 pediatric and 13 adult patients, with a median time from HSCT to TMA diagnosis of 81 days (range: 24-452 days) and a median time from TMA diagnosis to the first dose of narsoplimab of 3 days (range: 0-52 days). Diagnosis of TA-TMA was confirmed based on criteria that included a platelet count (PLT) of less than 150,000 µL, evidence of microangiopathic hemolysis (indicated by the presence of schistocytes, serum lactate dehydrogenase [LDH] exceeding the upper limit of normal [ULN], and/or haptoglobin below the lower limit of normal [LLN]), and renal dysfunction. The administered doses included 4 mg/kg for 24 patients and 370 mg for 4 patients, with a median number of administrations of 8 (range: 2-34) and a median duration of therapy of 8 weeks (range: 2-16 weeks). Efficacy was evaluated based on TMA response, defined as improvement in LDH (required to be less than 1.5 times ULN) and PLT counts, along with specific criteria based on baseline PLT levels, and either improvement in organ function or independence from transfusions. In the TA-TMA Study, a response was observed in 17 out of 28 patients (60.7%), with a 100-day survival rate from the time of TMA diagnosis of 73.4%. In the EAP, 13 out of 19 patients (68.4%) achieved a response, with a 100-day survival rate of 73.7%.
Yartemlea is the first FDA-approved treatment option for this condition. This approval was granted through priority review, Breakthrough Therapy Designation, and Orphan Drug Designation.
References
The above policy is based on the following references:
- Chaturveti S. Diagnostic approach to suspected TTP, HUS, or other thrombotic microangiopathy (TMA). UpToDate [online serial]. Waltham, MA: UpToDate; updated October 2025.
- Khaled SK, Claes K, Goh YT, et al. Narsoplimab, a mannan-binding lectin-associated serine protease-2 inhibitor, for the treatment of adult hematopoietic stem-cell transplantation-associated thrombotic microangiopathy. J Clin Oncol. 2022;40(22):2447-2457.
- Li A, Sartain SE. Transplant-associated TMA: The conundrum of diagnosis and treatment. Hematology Am Soc Hematol Educ Program. 2024;2024(1):206-213.
- Matsui H, Arai Y, Kanda J, et al. Survival in adults with high-risk TA-TMA: A comparative analysis of narsoplimab vs supportive care. Blood Adv. 2026;10(1):111-120.
- Omeros Corporation. Safety and efficacy study of OMS721 in patients with thrombotic microangiopathies. ClinicalTrials.gov Identifier: NCT02222545. Bethesda, MD: National Library of Medicine; updated August 28, 2024.
- Omeros Corporation. Single patient expanded access treatment plan for the investigational product narsoplimab. ClinicalTrials.gov Identifier: NCT04247906. Bethesda, MD: National Library of Medicine; updated December 2, 2025.
- Omeros Corporation. Yartemlea (narsoplimab-wuug) injection, for intravenous use. Prescribing Information. Seattle, WA: Omeros Coroporation; December 2025.
- Pandrowala A, Ganatra P, Krishnan VP, et al. Narsoplimab for severe transplant-associated thrombotic microangiopathy. Thromb J. 2023;21(1):26.
- Schoettler ML, Pusarla SK, Nangia N, et al. Narsoplimab results in excellent survival in adults and children with hematopoietic cell transplant associated thrombotic microangiopathy (TA-TMA). Am J Hematol. 2025;100(11):2040-2051.
- U.S. Food and Drug Administration (FDA). FDA approves first drug to treat serious complications of stem cell transplant. FDA News Release. Silver Spring, MD; January 5, 2026.
