On December 23, 2025, the U.S. Food and Drug Administration (FDA) approved Yartemlea (narsoplimab-wuug), a novel MASP-2 inhibitor developed by Omeros Corporation. This marks a significant regulatory milestone as Yartemlea is the first and only therapeutic indicated for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) in adult and pediatric patients one month of age and older.[1] The approval addresses a critical gap in transplant medicine, providing a targeted intervention for a complication that previously lacked any FDA-approved therapies.[2] Yartemlea was granted Priority Review, Breakthrough Therapy, and Orphan Drug designations, underscoring the urgency of the unmet medical need.[1]
Disease Context
TA-TMA is a devastating, systemic complication of hematopoietic stem cell transplantation (HSCT) characterized by widespread endothelial injury and microvascular thrombosis.[4] It affects a subset of allogeneic transplant recipients, with estimates of incidence ranging widely but often citing 10-20% in high-risk populations.[2]
Historically, the prognosis for high-risk TA-TMA has been dire. Without effective treatment, mortality rates can exceed 80%, often driven by multi-organ failure (renal, pulmonary, GI) and graft-versus-host disease (GvHD) complications.[5]
Prior to this approval, the standard of care was limited to supportive measures and the withdrawal of calcineurin inhibitors (CNIs).[5] While CNI withdrawal can ameliorate TMA, it significantly increases the risk of severe GvHD, creating a perilous clinical dilemma. Off-label use of terminal complement inhibitors (e.g., eculizumab) has been attempted, but response rates vary, and these agents carry significant infection risks due to terminal complement blockade.[6]
Mechanism of Action
Yartemlea is a fully human immunoglobulin G4 (IgG4) monoclonal antibody that targets mannan-binding lectin-associated serine protease-2 (MASP-2).[7]
- Target Specificity: MASP-2 is the effector enzyme of the lectin pathway of the complement system. This pathway is primarily triggered by tissue damage and microbial patterns, making it the central driver of the endothelial injury seen in TA-TMA.[2]
- Downstream Effects: By inhibiting MASP-2, Yartemlea prevents the cleavage of C4 and C2, thereby stopping the formation of C3 convertase via the lectin pathway. This halts the generation of the Membrane Attack Complex (MAC) on endothelial surfaces, reducing microvascular thrombosis and organ damage.[7]
- Differentiation: Unlike C5 inhibitors which block the terminal pathway (shared by all complement initiation routes), Yartemlea leaves the classical and alternative pathways intact.[2] This preservation is critical for maintaining host defense against pyogenic infections.
Analogy for Patients:
“Think of the immune system as a house with three different security alarms. In this disease, one specific alarm (the Lectin pathway) is malfunctioning and locking down the house, causing damage. Yartemlea acts like a master key that turns off only that broken alarm. Crucially, it leaves the other two alarms (Classical and Alternative pathways) active, so the security system can still detect and fight off intruders like bacteria.”
Clinical Trials
The FDA approval was based on efficacy data from the pivotal TA-TMA Study (OMS721-TMA-001) and supported by a confirmatory Expanded Access Program (EAP).[1]
Pivotal TA-TMA Study
- Design: A single-arm, open-label, multi-center trial enrolling 28 adult patients with high-risk TA-TMA.[7]
- Primary Endpoint: The primary efficacy outcome was Complete Response (CR), rigorously defined as improvement in laboratory markers (platelet count and LDH) plus clinical improvement (organ function recovery or transfusion independence).
- Result: The CR rate was 61% (95% CI: 40.6% – 78.5%).[8]
- Survival Analysis: The 100-day survival rate was 73% (95% CI: 52% – 86%).[2] When compared to an external control group derived from the KSCTG registry using Inverse Probability of Treatment Weighting (IPTW), Yartemlea demonstrated a Hazard Ratio (HR) for mortality of 0.32 (95% CI: 0.23 – 0.44), with a p-value of < 0.00001. This represents a 68% reduction in the risk of death.
Expanded Access Program (EAP)
- Design: A supportive cohort including adult and pediatric patients.
- Efficacy: In the evaluable efficacy population (N=19), the CR rate was 68%.[2]
- Subgroups: Pediatric patients (N=6 evaluable) achieved a CR rate of 67%, demonstrating consistency across age groups.[8]
Limitations
The primary limitation of the data package is the single-arm design lacking a concurrent placebo or active control arm.[7] The efficacy conclusions rely heavily on comparisons to historical external controls, which introduces potential bias regarding patient selection and supportive care standards. However, the FDA accepted this approach given the rarity of the condition and the high mortality rate in untreated patients.[8]
Also Read: Myqorzo (Aficamten): FDA-Approved Cardiac Myosin Inhibitor for Obstructive HCM
Safety Profile
The safety profile of Yartemlea reflects a critically ill population, yet lacks the restrictive regulatory mandates common to other complement inhibitors.
Adverse Reactions
Serious infections are the primary safety concern, occurring in 36% of patients in clinical trials.[7] The following table details Grade 3 adverse reactions reported in 15% of patients in the pivotal trial (N=28):
| Adverse Reaction | Incidence (Grade ≥ 3) | Source |
| Neutropenia | 36% | 7 |
| Sepsis | 21% | 7 |
| Pneumonia | 14% | 7 |
| Hypotension | 11% | 7 |
| Hypokalemia | 11% | 7 |
| Anemia | 11% | 7 |
Systemic Safety Summary
- Infections: While the classical pathway is preserved, the label warns of “Serious Infections” including sepsis, fungal infections, and pneumonia.[7] Fatal adverse reactions (neutropenic sepsis/septic shock) occurred in 7% of patients.[7]
- Discontinuation: Adverse reactions led to dosage interruption in 7% of patients. Permanent discontinuation rates due to drug-related AEs were low, reflecting the critical nature of the therapy.[7]
- Monitoring: Patients must be monitored for early signs of infection. If active infection is present, close surveillance is required, but treatment is not explicitly contraindicated.[7]
6. Practical Dosing
Standard Regimen
- Adults & Pediatric Patients 50 kg: 370 mg via IV infusion once weekly.[7]
- Pediatric Patients < 50 kg: 4 mg/kg via IV infusion once weekly.[7]
- Rationale: Weekly dosing maintains >80% inhibition of the lectin pathway.[1]
Modification Algorithms
- Escalation: If there is inadequate improvement in TA-TMA signs/symptoms, the frequency should be increased to twice weekly.[7]
- Renal/Hepatic Impairment: No specific dose adjustments are required.[7]
Role-Specific Notes
- Prescribers: Unlike C5 inhibitors, no pre-treatment meningococcal vaccination is required, allowing for immediate initiation upon diagnosis.[7]
- Pharmacists: The drug is supplied as a single-dose vial (370 mg/2 mL) and requires dilution. It is compatible with standard IV fluids.[7]
- Nurses: Administer as an IV infusion over 30 minutes. Monitor for infusion reactions, though they are rare.[7]
7. Patient Considerations
- Quality of Life: Successful treatment is associated with organ function recovery (renal, pulmonary, GI) in 74% of patients, significantly reducing the long-term burden of transplant complications like dialysis or oxygen dependence.[8]
- Treatment Burden: The median duration of therapy in trials was 8 weeks.[7] This is a finite course of therapy compared to the indefinite treatment often required for other complement-mediated diseases like PNH or aHUS.
- Selection: Suitable for patients meeting “high-risk” criteria: thrombocytopenia, microangiopathic hemolysis, and renal dysfunction.[7]
8. Regulatory Journey
The path to approval for Yartemlea was complex. Omeros originally received a Complete Response Letter (CRL) in October 2021, where the FDA cited difficulties in estimating the treatment effect size.[8] Omeros appealed and subsequently utilized an independent statistical group to analyze survival data against an external control registry. This analysis, showing a highly significant survival benefit (p < 0.00001), formed the basis of the successful resubmission in 2025. The drug holds Orphan Drug, Breakthrough Therapy, and Priority Review designations.[1]
9. Conclusion
The approval of Yartemlea represents a paradigm shift in the management of TA-TMA. By demonstrating a 61% complete response rate and a profound survival benefit (HR 0.32) in a population with historically dismal outcomes, it establishes a new standard of care.[2] Its safety profile—distinguished by the absence of a Black Box warning or REMS requirement—facilitates rapid integration into acute transplant care.[2] While vigilance for infection remains paramount, Yartemlea offers the first targeted, evidence-based lifeline for patients facing this life-threatening complication.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Consult full prescribing information for Yartemlea (narsoplimab-wuug) before prescribing.
Frequently Asked Questions (FAQs)
The Wholesale Acquisition Cost (WAC) is approximately $36,000 per single-dose vial. Since clinical trials showed a median utilization of 8 to 10 vials per treatment course, the total cost for a typical patient ranges between $288,000 and $360,000. Actual costs may vary based on patient weight and clinical response.
Currently, Yartemlea is not registered with the CDSCO for commercial sale in India. However, it can be accessed through Named Patient Supply (NPS). This legal pathway allows patients to import the medicine for personal use, provided they have a valid prescription from a qualified specialist and a government-issued import permit (Form 12B).
Yes. Omeros is launching YARTEMLEAssistâ„¢ in the first quarter of 2026. This program is designed to provide personalized support, including help with insurance verification and identifying financial assistance options for eligible patients. You can contact their support line at 1-844-YARTEM1 (1-844-927-8361) for guidance.
In the U.S., coverage is expected through major private insurers and Medicare. Omeros has established specific billing codes (ICD-10-CM: M31.11) to streamline claims. For international patients, coverage depends on specific “cross-border” or “critical illness” clauses in their policy. Patients are advised to request a “Pre-Authorization” from their provider before initiating the import process.
Currently, Yartemlea is FDA-approved only for patients 2 years of age and older. While clinical trials included some pediatric data, the safety and effectiveness for infants under the age of 2 have not yet been established. Use in this population would be considered “off-label” and should only be discussed under strict medical supervision.
A Marketing Authorization Application (MAA) is currently under review by the European Medicines Agency (EMA). A formal decision regarding approval and subsequent availability across the EU is expected in mid-2026.
Disclaimer: For informational purposes only. Consult full prescribing information. Availability and pricing are subject to regional regulatory changes.
References
- FDA Approves First Drug to Treat Serious Complication of Stem Cell Transplant. FDA News Release. December 24, 2025. Source URL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761152Orig1s000lbl.pdf
[3] - FDA Approves First Drug to Treat Serious Complication of Stem Cell Transplant. FDA News Release. December 24, 2025. Source URL: https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-drug-treat-serious-complication-stem-cell-transplant
[1] - Omeros Corporation. FDA Approves Omeros’ YARTEMLEA® – First and Only Therapy Indicated for TA-TMA. Business Wire. December 24, 2025. Source URL: https://investor.omeros.com/news-releases/news-release-details/fda-approves-omeros-yartemlear-first-and-only-therapy-indicated
[2] - YARTEMLEA (narsoplimab-wuug) [Prescribing Information]. Omeros Corporation. December 2025. Source URL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761152Orig1s000lbl.pdf
[3] - Omeros Corporation. Omeros’ Narsoplimab Meets its Pivotal Trial Primary Endpoint – Statistical Analysis Shows Survival Superiority Over External Control in Patients with TA-TMA. December 19, 2024. Source URL: https://www.sec.gov/Archives/edgar/data/1285819/000143774924037898/ex_755914.htm “
- Schoettler M, et al. Narsoplimab Results in Excellent Survival in Adults and Children With Hematopoietic Cell Transplant Associated Thrombotic Microangiopathy (TA-TMA). Am J Hematol. 2025. Source URL: https://pubmed.ncbi.nlm.nih.gov/40880162/ “
- DelveInsight. Omeros’ Yartemlea for TA-TMA. Source URL: https://www.delveinsight.com/blog/omeros-yartemlea-for-ta-tma
[4] - Seeking Alpha. Omeros Corporation (OMER) Discusses FDA Approval and Commercialization Plans for YARTEMLEA. January 7, 2026. Source URL: https://seekingalpha.com/article/4857866-omeros-corporation-omer-discusses-fda-approval-and-commercialization-plans-for-yartemlea-in
[5] - FDA Access Data. Labeling for Yartemlea (BLA 761152). Source URL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761152Orig1s000lbl.pdf
[3]
