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

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

Narsoplimab Treatment for Hematopoietic Cell Transplant Associated Thrombotic Microangiopathy (TA-TMA) – Real World Outcomes from an Expanded Access Program (TCT-ASTCT-CIBMTR 2025) - "In the HRAS cohort, 36 (36.0%) patients were confirmed to have failed eculizumab, with some failing >1 alternative therapy regimen prior to initiating narsoplimab. 128 allogeneic recipients (Full Analysis Set, FAS) were enrolled: 77 adults, median age 51.7 yrs (range 19 – 72), and 51 children, median age 10.1 yrs (range 0 – 18); 67 were male (52.3%). Median time of TA-TMA diagnosis was 98 days post HCT (range 0 – 1042). Risk stratification data were available in 102 patients of whom 100 (98.0%) – the High-Risk Analysis Subset (HRAS) – were confirmed to have had ≥1 HR feature with 80 (80.0%) having ≥2 ( Schoettler et al."

Clinical • Real-world • Real-world evidence • Acute Graft versus Host Disease • Cardiovascular • Graft versus Host Disease • Hematological Disorders • Hypertension • Immunology • Infectious Disease • Thrombocytopenia • Transplantation • HRAS

Omeros Announces Update on Statistical Analysis of Narsoplimab Pivotal Trial Primary Endpoint (Businesswire) - P2 | N=18 | NCT05855083 | Sponsor: Omeros Corporation | "Sensitivity analyses support the results of the primary endpoint analysis...Narsoplimab-treated patients had an over 2-fold reduction (hazard ratio = 0.42 [95% confidence interval: 0.21, 0.83]) to an over 4-fold reduction (hazard ratio = 0.24 [95% confidence interval: 0.13, 0.47] in risk of mortality; P-values ranging from 0.0124 to < 0.00001; The primary endpoint analysis, previously reported on December 19, 2024, showed an over 3-fold reduction in risk of mortality (hazard ratio = 0.32 [95% confidence interval: 0.23, 0.44]; p < 0.00001) in TA-TMA patients treated with narsoplimab compared to the external control registry TA-TMA patients not treated with narsoplimab; Omeros plans to resubmit to FDA later this quarter the BLA for narsoplimab to become the first approved therapeutic for TA-TMA...MAA submission to European regulators targeted by mid-year..."

EMA filing • FDA filing • P2 data • Transplantation

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 • CNS Tumor • Hematological Disorders • Hypertension • Nephrology • Neuroblastoma • Oncology • Pediatrics • Renal Disease • Solid Tumor • Thrombocytopenia • Transplantation • HP

A review of progress on complement and primary membranous nephropathy. (PubMed, Medicine (Baltimore)) - "Several clinical trials are presently underway to evaluate the efficacy of complement inhibitors, such as MASP2 antagonists (OMS721), C3 and C3b antagonists (APL2), FD inhibitors (BCX9930), C3aR antagonists (SB290157 and JR14a), FB inhibitors (LNP023). This article reviews the recent research progress on the role of the complement pathway in the pathogenesis of PMN, and underscores the importance of continued research into the complement pathway and its inhibitors, which may pave the way for groundbreaking advancements in the management of PMN."

Journal • Review • Glomerulonephritis • Nephrology • Renal Disease

Omeros Corporation Further Strengthens its Balance Sheet through Series of Financing Transactions Extending Maturity on a Majority of its Outstanding Debt into 2028 (Businesswire) - "Credit facility includes $25 million delayed draw term loan conditionally available to fund narsoplimab commercialization....The $25.0 million delayed draw term loan may be drawn once in full on or prior to June 3, 2025, conditioned on receipt of approval from the U.S. Food and Drug Administration of narsoplimab in hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA). Proceeds of the delayed draw term loan, if borrowed, must be used to fund the commercialization of narsoplimab and to pay transaction costs associated with the delayed draw term loan."

Commercial • Rare Diseases

A Case of Eculizumab-Refractory Transplant-Associated Thrombotic Microangiopathy Responsive to Narsoplimab (NKF-SCM 2024) - "Despite high morbidity and mortality associated with TA-TMA, best practice for management remains unclear. We describe a patient with high-risk TA-TMA refractory to Eculizumab. Narsoplimab was subsequently used with evidence of response."

Clinical • Acute Kidney Injury • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Cardiovascular • Hematological Disorders • Infectious Disease • Inflammation • Ischemic stroke • Nephrology • Renal Disease • Thrombocytopenia • Thrombosis • Transplantation • HP

Safety and efficacy of narsoplimab in pediatric and adult patients with transplant-associated thrombotic microangiopathy: a real-world experience. (PubMed, Bone Marrow Transplant) - "Narsoplimab proved to be effective and safe in the treatment of high-risk TA-TMA, with no increased infectious complications or other safety signals of concern across all age groups. The high response rates and the encouraging survival outcomes underscore the potential of narsoplimab as a valuable therapeutic option, particularly for high-risk cases."

Journal • Real-world • Real-world evidence • Bone Marrow Transplantation • Pediatrics • Transplantation

Omeros Corporation Reports First Quarter 2024 Financial Results (Businesswire) - "We continue working toward a resubmission of our biologics license application ('BLA') for narsoplimab in hematopoietic stem cell transplant-associated thrombotic microangiopathy ('TA-TMA')....We continue to engage with FDA regarding the analysis plan and other expectations for resubmission of our BLA....A manuscript directed to the outcome of narsoplimab treatment in 20 real-world adult and pediatric patients – 19 of whom had high-risk characteristics – is expected to be published soon in the Nature journal Bone Marrow Transplantation....Recent developments regarding OMS527, our phosphodiesterase 7 ('PDE7') inhibitor program focused on addictions and compulsive disorders as well as movement disorders....We expect to complete the preclinical cocaine interaction study by the end of 2024."

Clinical • FDA filing • Preclinical • Anemia • Bone Marrow Transplantation • Hematological Disorders • Nicotine Addiction

Vulnerable Vessels: Microvascular Disease in Post-Transplant AYA Patients with Diamond-Blackfan Anemia (ASPHO 2024) - "Patient 1 received defibrotide prophylaxis to prevent sinusoidal obstructive syndrome (SOS) and had an uncomplicated clinical course post-transplant...TA-TMA treatment with eculizumab was followed by narsoplimab administration due to an unsatisfactory clinical response... We present four AYA patients who underwent HSCT for DBA. Three patients (75%) developed severe microvascular disease and two (66%) succumbed to this complication. In addition, genetic mutations were only identified in 50% of the patients."

Clinical • Post-transplantation • Acute Graft versus Host Disease • Anemia • Bone Marrow Transplantation • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hypertension • Immunology • Infectious Disease • Myelodysplastic Syndrome • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thrombocytopenia • Transplantation

BI-FUNCTIONAL C5 ANTIBODY-FUSION PROTEIN (LP-005) WITH POTENTIAL BEST-IN-CLASS BIOACTIVITY FOR COMPLEMENT INHIBITION (ISN-WCN 2024) - " The sequence of Eculizumab, Ravulizumab, Crovalimab, Pozelimab, Narsoplimab, were obtained from INN. In summary, LP-005 is a novel bifunctional anti-C5 monoclonal antibody fusion protein, with highest bioactivity in CP, AP, LP. LP-005 is also engineered to change it surface charge (PI) and FcRn binding, which together has the potential to be a bestin-class drug candidate with improved pharmacokinetic properties and strongest in-vitro and in-vivo bioactivity."

CNS Disorders • Glomerulonephritis • Hematological Disorders • IgA Nephropathy • Inflammatory Arthritis • Lupus • Nephrology • Renal Disease

I-SPY_COVID: I-SPY COVID-19 TRIAL: An Adaptive Platform Trial for Critically Ill Patients (clinicaltrials.gov) - P2 | N=1500 | Recruiting | Sponsor: QuantumLeap Healthcare Collaborative | Trial completion date: Nov 2024 ➔ Jul 2030 | Trial primary completion date: Jul 2023 ➔ Jul 2028

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

ARTEMIS - IGA: Study of the Safety and Efficacy of OMS721 in Patients With Immunoglobulin A (IgA) Nephropathy (clinicaltrials.gov) - P3 | N=356 | Terminated | Sponsor: Omeros Corporation | Trial completion date: Apr 2023 ➔ Oct 2023 | Recruiting ➔ Terminated | Trial primary completion date: Aug 2020 ➔ Oct 2023; IA did not show positive results. Study is terminated, and in process of closing

Trial completion date • Trial primary completion date • Trial termination • Glomerulonephritis • IgA Nephropathy • Renal Disease

Successful use of narsoplimab to treat allogeneic transplant-associated thrombotic microangiopathy while maintaining sirolimus. (PubMed, Bone Marrow Transplant) - No abstract available

Journal • Transplantation

Advances in the treatment of IgA nephropathy with biological agents. (PubMed, Chronic Dis Transl Med) - "There are four main categories of biological agents used to treat IgA nephropathy, specifically anti-CD20 monoclonal antibodies, anti-BLyS or APRIL monoclonal antibodies, monoclonal antibodies targeting both BLyS and APRIL (telitacicept and atacicept), and monoclonal antibodies inhibiting complement system activation (narsoplimab and eculizumab). However, further research on the dosages, treatment duration, long-term efficacy, and safety of these biological agents is required."

Journal • Review • Glomerulonephritis • IgA Nephropathy • Infectious Disease • Nephrology • Renal Disease

Real-World Experience with Narsoplimab (OMS721) for the Treatment of Transplant-Associated Thrombotic Microangiopathy (TCT-ASTCT-CIBMTR 2024) - "One patient had a partial response to narsoplimab at 5 weeks and was subsequently changed to eculizumab, and after an extended treatment, achieved a complete response. Narsoplimab can be administered safely without significant adverse events and can result in clinical resolution of TA-TMA with durable response. Six patients in this cohort had major ABO incompatibility making transfusion independence a poor predictor of response. Haptoglobin was paradoxically increased, likely as an acute phase reactant, in patients with acute GVHD."

Clinical • Real-world • Real-world evidence • Acute Graft versus Host Disease • Febrile Neutropenia • Graft versus Host Disease • Hematological Disorders • Immunology • Neutropenia • Thrombocytopenia • Transplantation • HP

I-SPY_COVID: I-SPY COVID-19 TRIAL: An Adaptive Platform Trial for Critically Ill Patients (clinicaltrials.gov) - P2 | N=1500 | Recruiting | Sponsor: QuantumLeap Healthcare Collaborative | Trial completion date: Nov 2023 ➔ Nov 2024

Trial completion date • Infectious Disease • Novel Coronavirus Disease

Efficacy and Safety Study of Narsoplimab in Pediatric Patients With High-Risk Hematopoietic Stem Cell Transplant TMA (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: Omeros Corporation

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Pediatrics • Transplantation

Compassionate Use Narsoplimab for Severe, Refractory Transplant Associated Thrombotic Microangiopathy in Children. (PubMed, Transplant Cell Ther) - "In this cohort of ill children with rTA-TMA and multiple comorbidities, 3 patients benefitted from narsoplimab. Notably, the 2 patients with resolution of organ involvement did not have steroid refractory acute GVHD, which is thought to be a critical driver of TA-TMA. Additional studies are needed to determine which patients are most likely to benefit from narsoplimab and which markers may be most helpful to monitor lectin pathway activation and inhibition."

Journal • Acute Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • Transplantation