narsoplimab (OMS721) / Omeros, University of Leicester, Helion Biotech - LARVOL DELTA

Complement inhibition in post-transplant IgA-mediated autoimmune cytopenia: A pediatric case report (ASH 2025) - "He developed cellular rejection one-year post-transplant and was treated with cyclosporine and MMF. At 7 years post-transplantation, he developed acute cellular rejection with third-degree heart block requiring pulse steroids and ATG, with subsequent transition to tacrolimus/sirolimus...Modification of immunosuppression is particularly challenging in the post solid organ transplant setting and can risk organ rejection requiring close collaboration with primary transplant team.⁵⁻⁶ In IgA-driven diseases like IgA nephropathy, complement inhibitors (e.g., eculizumab, narsoplimab) are gaining traction.⁷ This case adds to emerging evidence that complement modulation is a viable treatment pathway for refractory IgA-mediated AIHA, especially in the post-transplant setting. Eculizumab with prednisone was effective and well-tolerated in this case of IgA-mediated, rituximab-refractory AIHA post-heart transplant. Complement inhibition may represent a novel and safe therapeutic..."

Case report • Clinical • Post-transplantation • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • IgA Nephropathy • Immunology • Pediatrics • Renal Disease • Solid Organ Transplantation • Thrombocytopenia • Transplantation

aHUS: Safety and Efficacy Study of OMS721 in Patients With Atypical Hemolytic Uremic Syndrome (clinicaltrials.gov) - P3 | N=6 | Terminated | Sponsor: Omeros Corporation | N=80 ➔ 6 | Unknown status ➔ Terminated; Sponsor terminated study

Enrollment change • Trial termination • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Hematological Disorders • Nephrology • HP

Characterization of a Long-Acting Anti-Human MASP-2 Antibody for the Treatment of Complement-Related Diseases. (PubMed, J Inflamm Res) - "Preclinical studies demonstrated that SHR-2010 exhibited superior pharmacokinetics and sustained lectin pathway inhibition compared to OMS721. When coupled with optimized trial design strategies, SHR-2010 could be a promising therapeutic candidate for lectin pathway-driven diseases, including IgAN."

Journal • Acute Kidney Injury • Bone Marrow Transplantation • Glomerulonephritis • IgA Nephropathy • Inflammation • Nephrology • Rare Diseases • Renal Disease • Transplantation

Transplant Associated Thrombotic Microangiopathy: Acomprehensive Review and Local Experience (ASH 2023) - "eculizumab, a humanized antibody against complement protein, can be highly effective in patients with TA-TMA...Other available treatment options include rituximab and defibrotide. Other therapeutic agents are under clinical trials such as ravulizumab (C5 inhibitor), nomacopan (C5 and leukotriene B4 inhibitor) and narsoplimab (mannan-binding lectin-associated serine protease-2 [MASP-2] inhibitor)...Thus far, the choice is to individualize therapy according to comorbidities, severity of clinical presentation and availability of the treatment options. ConclusionTA-TMA remains a significant clinical challenge for transplant physicians, and more research is needed to improve our understanding of its pathogenesis, diagnosis, and management, particularly in guiding the choice of therapy."

Review • Anemia • Bone Marrow Transplantation • Cardiovascular • Graft versus Host Disease • Hematological Disorders • Hypertension • Immunology • Infectious Disease • Thrombocytopenia • Transplantation

Clinical Safety and Efficacy of Narsoplimab in Pediatric and Adult Patients with Transplant-Associated Thrombotic Microangiopathy: A Real-World Experience (ASH 2023) - "Three of the four patients who failed to respond, eventually died with laboratory and clinical evidence of persisting TA-TMA. Conclusion In this study of high-risk TA-TMA patients, the inhibition of the lectin pathway of complement activation with narsoplimab was shown to be not only an effective but also a remarkably safe treatment option with no evidence of an increased risk of infectious complications in both children and adults."

Clinical • Real-world • Real-world evidence • Acute Graft versus Host Disease • Anemia • Bone Marrow Transplantation • Cardiovascular • Graft versus Host Disease • Hematological Disorders • Hypertension • Immunology • Infectious Disease • Pediatrics • Thrombocytopenia • Transplantation • HP

Management of a Complex Case of Transplant-Associated Thrombotic Microangiopathy in a Pediatric Patient with High-Risk Neuroblastoma (ASH 2024) - "Initial treatment included Eculizumab with minimal response. Treatment was changed to Narsoplimab (OMS721), and Defibrotide was added with minimal response...Defibrotide was discontinued, and further therapy with plasmapheresis/PLEX (Plasma Exchange) and Rituximab was added...The case underscores the necessity of a multidisciplinary approach to address TA-TMA and highlights the importance of adjusting therapy based on the response.ConclusionTA-TMA in patients with high-risk neuroblastoma is rare but is a serious complication of treatment, and the management is complex. This case demonstrates the need for a coordinated, personalized treatment strategy to optimize treatment outcomes."

Clinical • Anemia • Bone Marrow Transplantation • Cardiovascular • Hematological Disorders • Hypertension • Nephrology • Neuroblastoma • Oncology • Pediatrics • Renal Disease • Solid Tumor • Thrombocytopenia • Transplantation • HP

Survival in Adults with High Risk TA-TMA - A Comparative Analysis of Narsoplimab Versus Supportive Care. (PubMed, Blood Adv) - P, P2 | "In conclusion, in patients with high-risk TA-TMA, narsoplimab treatment significantly reduced mortality relative to a well-matched external control group who did not receive narsoplimab. These results support narsoplimab as a potential therapeutic option for TA-TMA."

Journal • Bone Marrow Transplantation • Transplantation

The FDA has assigned a PDUFA target action date of December 26, 2025, for its review of narsoplimab in the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy/TA-TMA. (RTTNews)

PDUFA • Transplantation

Omeros Announces Publication Highlighting Survival Outcomes in TA-TMA Patients Treated with Narsoplimab Under Its Global Expanded Access Program (Yahoo Finance) - "Authored by an international panel of pediatric and adult transplant experts, the manuscript – titled 'Narsoplimab Results in Excellent Survival in Adults and Children with Hematopoietic Cell Transplant Associated Thrombotic Microangiopathy (TA-TMA)' – reports survival outcomes in patients treated with narsoplimab as first-line therapy and in those who failed prior treatments, including C5 inhibitors. Consistent with previous narsoplimab clinical studies, no safety signals of concern were observed."

Clinical data • Transplantation

Narsoplimab Results in Excellent Survival in Adults and Children With Hematopoietic Cell Transplant Associated Thrombotic Microangiopathy (TA-TMA). (PubMed, Am J Hematol) - "One-year overall survival (OS) in pediatric allogeneic recipients with HR TA-TMA who received narsoplimab as first-line therapy (n = 12) was 75.0% and 56.2% in those who received treatment as ≥ second-line (n = 25, 20 refractory to eculizumab). There were no concerning safety signals. In this real-world study enriched with patients with severe TA-TMA, survival was excellent in children and adults, supporting the use of narsoplimab."

Journal • Oncology • Pediatrics • Solid Tumor • Transplantation

FDA delays Omeros' 2nd attempt at transplant drug's approval by 3 months (FierceBiotech) - "Omeros had been given a deadline of Sept. 25 for the agency to reconsider whether to approve the anti-MASP-2 antibody narsoplimab for hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA)...The FDA had requested further information in relation to Omeros’ application and, after receiving the biotech’s response, informed the company that the decision date has been pushed back to Dec. 26...The agency explained that 'assuming no major deficiencies are identified during its review, labeling discussions are planned to begin no later than Oct. 2025'..."

FDA event • PDUFA • Transplantation

Targeting the Roots of Kidney Disease: Systematic Review of the Therapies Targeting the Complement System. (PubMed, Medicina (Kaunas)) - "Meanwhile, avacopan, a C5a receptor antagonist, addresses ANCA-associated vasculitis (AAV) by mitigating inflammation and enabling reduced reliance on corticosteroids. Similarly, narsoplimab, which inhibits MASP-2, targets the lectin pathway implicated in conditions such as aHUS. Iptacopan, a factor B inhibitor, focuses on the alternative pathway and demonstrates efficacy in managing C3 glomerulopathy (C3G). A systematic review of complement-targeted therapies was conducted, analysing studies from 2013 to 2023 that address unmet medical needs in primary and secondary glomerular diseases. Our systematic review of complement-targeted therapies shows that these tailored and innovative treatments may specifically address unmet medical needs in primary and secondary glomerular diseases."

Journal • Review • ANCA Vasculitis • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • Inflammation • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Vasculitis

Complement Inhibition in IgA Nephropathy (KSN 2025) - "In a phase 3 trial, iptacopan achieved a ~38% greater reduction in proteinuria versus placebo at 9 months on top of standard care, leading to its accelerated approval as the first complement inhibitor for IgAN. An antisense oligonucleotide targeting factor B (IONIS-FB-LRx) similarly reduced proteinuria by ~44% in a phase 2 study, and a phase 3 trial is ongoing. In contrast, the lectin pathway inhibitor narsoplimab (anti-MASP-2) did not meet its primary endpoint in a phase 3 trial, despite promising early-phase results. We will also discuss other investigational approaches, including proximal complement blockade at C3 (pegcetacoplan) and terminal pathway inhibition (e.g., C5 monoclonal antibodies and C5a receptor antagonists). While terminal complement inhibitors like eculizumab have shown anecdotal benefits in severe IgAN, robust trial data in primary IgAN are awaited...While targeting the alternative pathway has shown the most consistent benefit to date, additional..."

Fibrosis • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammation • Lupus Nephritis • Renal Disease

Omeros Submits Narsoplimab Marketing Authorization Application to the European Medicines Agency for the Treatment of TA-TMA (Businesswire) - "Omeros Corporation...announced the recent submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for narsoplimab for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA)...The MAA includes response-based analyses in narsoplimab-treated TA-TMA patients as well as analyses comparing overall survival between narsoplimab-treated patients and a well-matched external control group...The submission also includes outcomes in over 130 TA-TMA patients treated with narsoplimab under Omeros’ expanded access program....The review procedure begins in mid-July and will follow a standard review timeline. The Committee for Medicinal Products for Human Use (CHMP) will conduct the scientific assessment and will issue an opinion at the end of the review. This opinion is typically adopted by the European Commission, with a final decision expected in mid-2026."

EMA approval • EMA filing • Hematological Disorders • Transplantation

Translating biomarker insights into practice: a path forward in TA-TMA management. (PubMed, Front Med (Lausanne)) - "Eculizumab therapy, a biomarker-guided C5 blocker, significantly improves clinical outcomes in severe TA-TMA; however, there is a lack of knowledge on how to select second-line complement inhibitors or combination therapies for cases with a suboptimal response to eculizumab. This article proposes practical approaches to increasing the specificity and attributability of TA-TMA diagnostic biomarkers by integrating clinically available supportive diagnostic tests and provides insights into potential biomarkers for currently available novel complement inhibitors. These findings help ensure timely diagnosis, prevent irreversible organ injury, and improve outcomes in HSCT recipients with TA-TMA."

Biomarker • Journal • Bone Marrow Transplantation • Hematological Disorders • Transplantation

Complex Case of Transplant-Associated Thrombotic Microangiopathy in High-Risk Neuroblastoma (ASPHO 2025) - "Initially, Eculizumab was used with minimal response, followed by Narsoplimab (OMS721) and Defibrotide, with only slight improvement...Despite treatment, minimal response was observed, and therapy was adjusted to include plasmapheresis/PLEX and Rituximab, which led to significant improvement... TA-TMA is a rare but severe complication of hematopoietic stem cell transplantation, leading to endothelial damage and complement dysregulation, causing microvascular hemolytic anemia and end-organ dysfunction. Early recognition and treatment are essential to reduce morbidity and mortality. This case highlights the challenges in managing high-risk neuroblastoma complicated by TA-TMA."

Clinical • Anemia • Bone Marrow Transplantation • Cardiovascular • Hematological Disorders • Hypertension • Nephrology • Neuroblastoma • Oncology • Renal Disease • Solid Tumor • Thrombocytopenia • Transplantation • HP

FDA Accepts Resubmission of BLA for Narsoplimab for Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (TA-TMA) and Assigns Late September PDUFA Date (Businesswire) - "Omeros Corporation...today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the resubmission of the Biologics License Application (BLA) for narsoplimab for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA). The resubmission was classified as a Class 2 resubmission and pursuant to the Prescription Drug User Fee Act (PDUFA) has been assigned a target action date for the FDA decision in late September 2025....Omeros is also preparing a marketing authorization application (MAA) for narsoplimab in TA-TMA, which is targeted for submission to the European Medicines Agency later this quarter."

FDA filing • PDUFA • Transplantation

Narsoplimab for refractory transplantation-associated thrombotic microangiopathy (TA-TMA) in adult patients receiving allogeneic hematopoietic stem cell transplantation (AHSCT). (PubMed, Bone Marrow Transplant) - No abstract available

Journal • Bone Marrow Transplantation • Transplantation

TRANSPLANT-ASSOCIATED THROMBOTIC MICROANGIOPATHY: CLINICAL EXPERIENCE AND OUTCOMES (EBMT 2025) - "Outcomes for TA-TMA remain poor, with better responses to complement directed therapies like Eculizumab and Narsoplimab than plasma exchange. Our study aims to evaluate the incidence, clinical features, risk factors, and outcomes of TA-TMA in our center, in a resource limited setting where we do not have routine access to tests like serum C5b-9 and therapies like Defibrotide and Eculizumab...All patients received post-transplant cyclophosphamide (PTCy) along with a CNI (which was on-going at the time of TA-TMA diagnosis) and mycophenolate mofetil as GVHD prophylaxis...Six patients had CMV reactivation at the time of onset of TA-TMA and were on ganciclovir or valganciclovir therapy... TA-TMA is not as uncommon as previously thought, especially after haplo-HSCT. Older age, onset earlier in the post-HSCT course and higher LDH at diagnosis were associated with increased risk of mortality in our cohort. A proactive screening based on HSCT risk factors may help in earlier..."

Clinical • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Cardiovascular • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Nephrology • Thrombocytopenia • Thrombosis • Transplantation

THERAPY-RESISTANT TRANSPLANT-ASSOCIATED THROMBOTIC MICROANGIOPATHY IN A PEDIATRIC PATIENT (SCCM 2025) - "Despite a prolonged course of monoclonal antibody treatment with Eculizumab and Ravulizumab, her condition continued to deteriorate. She also received complementary treatment with methylprednisolone, acetylcysteine, Rituximab and Basiliximab. Although her TMA has been persistently treated, her TMA markers worsen, for this reason compassionate use of Narsoplimab was recommended...This case emphasizes the need for a multidisciplinary approach including Hematologist, Oncologist, Nephrologist, Transplant team and Critical Care. In addition, it stresses the importance of further research into TA-TMA and its treatment options."

Clinical • Anemia • Bone Marrow Transplantation • Cardiovascular • CNS Tumor • Gastrointestinal Disorder • Hematological Disorders • Hypertension • Metabolic Disorders • Nephrology • Neuroblastoma • Oncology • Pediatrics • Renal Disease • Solid Tumor • Thrombocytopenia • Transplantation • HP

Omeros Announces Robust Results for Narsoplimab Expanded Access Program in TA-TMA (Businesswire) - "'The results from the expanded access program are further compelling evidence of the effectiveness of narsoplimab in TA-TMA,' stated Miguel-Angel Perales, MD...'The EAP accepted all-comers globally - adult and pediatric patients in the real-world setting. Many are representative of the most challenging patients that we at MSKCC and the community of transplant experts worldwide regularly attempt to treat. With the now overwhelming clinical survival data and the absence of any identified safety signal, there is a clear need for narsoplimab in the treatment of our patients with TA-TMA, and we look forward to the drug’s rapid approval.'"

Media quote

Omeros Announces Robust Results for Narsoplimab Expanded Access Program in TA-TMA (Businesswire) - P2 | N=49 | NCT04247906 | Sponosr: Omeros Corporation | "The results from these analyses further support the robustness of the previously reported results from the statistical analysis plan agreed with FDA, with representative analyses of the combined EAP and pivotal trial patients yielding hazard ratios ranging from 0.34 (95 percent confidence interval: 0.21, 0.53) to 0.46 (95 percent confidence interval: 0.35, 0.60) and p-values ranging from less than 0.00001 to 0.00002. Consistent with all previous clinical experience with narsoplimab, no safety signals of concern were observed...Overall survival using Inverse Probability of Treatment Weighting (IPTW) with all specified risk factors: Hazard ratio = 0.37 (95 percent confidence interval: 0.28, 0.48)...Overall survival using IPTW with only treatment as a factor: Hazard ratio = 0.46 (95 percent confidence interval: 0.35, 0.60)."

P2 data • Immunology • Transplantation

Omeros Corporation Announces Availability on its Website of Materials Accompanying Narsoplimab Presentations at the 2025 Tandem Meetings (Businesswire) - "Omeros Corporation...today announced the availability on its website of materials accompanying two presentations given at the 2025 Tandem Meetings – the Transplantation & Cellular Therapy Meetings of the American Society for Transplantation and Cellular Therapy and the Center for International Blood and Marrow Transplant Research...The slides accompanying a presentation by Michelle Schoettler, M.D., Assistant Professor of Pediatric Oncology and Hematopoietic Cellular Therapy at Emory University, of overall survival data from 128 allogeneic transplant patients with TA-TMA treated with narsoplimab under the expanded access program. The poster presented by Piyatida Chumnumsiriwath, M.D., of the Hematopoietic Stem Cell Transplantation and Cellular Therapy Program at the University of California, Irvine, reporting outcomes from a single-center cohort of adult TA-TMA patients who were treated with narsoplimab after failing eculizumab treatment."

Clinical • Transplantation

Omeros Corporation Announces Upcoming Presentations Detailing Outcomes of Narsoplimab Treatment for TA-TMA Under an Expanded Access Program (Businesswire) - "Omeros Corporation...today announced two presentations that will be featured at the 2025 Tandem Meetings – the Transplantation & Cellular Therapy Meetings of the American Society for Transplantation and Cellular Therapy and the Center for International Blood and Marrow Transplant Research, to be held February 12-15, 2025 in Honolulu, Hawaii. Both presentations report real world outcomes from patients with hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) treated with narsoplimab supplied by Omeros under an expanded access program, also referred to as compassionate use. The first reports overall survival of 128 allogeneic transplant patients with TA-TMA treated with narsoplimab under the expanded access program...The second reports on a single-center cohort of adult TA-TMA patients who were treated with narsoplimab after failing eculizumab treatment."

Clinical • Real-world • Hematological Disorders

Narsoplimab for Refractory Transplantation-Associated Thrombotic Microangiopathy (TA-TMA) in Adult Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT) (TCT-ASTCT-CIBMTR 2025) - "Patients with TA-TMA refractory to eculizumab appear to respond to narsoplimab with improvement in fluid retention and MODS. A prospective study is warranted to further explore these findings."

Clinical • Acute Kidney Injury • Bone Marrow Transplantation • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Hypertension • Nephrology • Pain • Renal Disease • Transplantation • HP