Epysqli (eculizumab-aagh) / AffaMed Therap, Samsung, Teva - LARVOL DELTA

Long-term therapy with eculizumab biosimilar in patients with paroxysmal nocturnal hemoglobinuria: Two-year interim results of a prospective multicenter observational study (ASH 2025) - "Introduction: The complement C5-inhibition with eculizumab or ravulizumab is a current standard of care in patients with paroxysmal nocturnal hemoglobinuria (PNH)...The prospective multicenter observational study ECU-PNH-N02 was initiated to evaluate the results of long-term therapy with a biosimilar of eculizumab (Elizaria®) in a Russian cohort of patients with PNH in accordance with national treatment protocols... Thus, the results of the study indicate a long-term stable course of PNH during safe and effective treatment with a biosimilar of eculizumab. Acknowledgments: The authors thank all the investigators and patients who participated and continues to participate in this study."

Clinical • Observational data • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Pneumonia • Rare Diseases • Respiratory Diseases

The use of danicopan as an add-on therapy in a ravulizumab-treated adult patient with paroxysmal nocturnal hemoglobinuria (PNH) and concomitant stage IV renal failure has induced a marked improvement of anemia and of clinically significant extravascular hemolysis in absence of deterioration of renal function (ASH 2025) - "In 2019, this patient was treated with biosimilar eculizumab (phase 3 trial- ABP959-Amgen) till spring 2022. In conclusion, danicopan has demonstrated high efficacy in increasing hemoglobin level (range 2.3-3 g/dL), and reducing markers of hemolysis in a PNH patient with concomitant stage IV renal failure, having an inadequate hematological response to either eculizumab or ravulizumab (hemoglobin <9•5 g/dL). Interestingly, renal function was not affected by the combined use of ravulizumab and danicopan, during a 11 months- follow-up observation period."

Clinical • Metastases • Anemia • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Endocrine Disorders • Hematological Disorders • Hypertension • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Thrombosis

Study design of A phase 3, open-label trial for pozelimab and cemdisiran combination therapy in patients with paroxysmal nocturnal hemoglobinuria with inadequate control of intravascular hemolysis (ASH 2025) - "Treatment for PNH includes C5 inhibitorssuch as eculizumab/biosimilar, ravulizumab, and crovalimab, however, patients under terminalcomplement inhibition can experience residual intravascular hemolysis due to incomplete C5 blockade.The combination of pozelimab (a monoclonal antibody that prevents activation of C5) and cemdisiran (asilencing RNA that reduces production of circulating C5) is a novel approach being investigated for itsability to achieve durable inhibition of the terminal complement pathway. During the ext period, the secondary endpoints willinclude percent change in LDH from baseline to ext week 24 and ext week 52, normalization of LDH ateach visit through ext week 52, inclusive, and adequate control of hemolysis at each visit through extweek 52. Recruitment for this study is expected to begin around November 2025."

Clinical • Combination therapy • P3 data • Bone Marrow Transplantation • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Efficacy of SB12 (Eculizumab Biosimilar) in Asian and Non-Asian Patients with Paroxysmal Nocturnal Hemoglobinuria: Subgroup Analysis of a Global Phase III Randomized Controlled Trial (ASH 2023) - "Conclusion SB12 showed comparable efficacy to ECU in complement-inhibitor naïve PNH patients in both Asian and Non-Asian subgroups. No patient developed anti-drug antibodies nor discontinued due to lack of efficacy during the study period."

Clinical • P3 data • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Efficacy of Parallel and Crossover Analysis As Well As Pharmacokinetic Similarity Were Confirmed between ABP 959 and Eculizumab Reference Product in Patients with PNH (ASH 2023) - "Introduction: ABP 959, a biosimilar to eculizumab reference product (RP), binds to the human complement component 5 protein to inhibit terminal complement activation. Similarity in clinical efficacy in both parallel and crossover comparisons as determined by hemolysis in patients with PNH was established between ABP 959 and eculizumab RP. Additionally, analyses of serum total and unbound PK concentrations for patients with PNH further demonstrated PK similarity between ABP 959 and eculizumab RP. The results of this study, along with previously demonstrated analytical, non-clinical, clinical PK/PD in healthy adults, and efficacy and safety evaluations in PNH patients, further support a demonstration of no clinically meaningful differences between ABP 959 and eculizumab RP."

Clinical • PK/PD data • Atypical Hemolytic Uremic Syndrome • CNS Disorders • Complement-mediated Rare Disorders • Hematological Disorders • Myasthenia Gravis • Nephrology • Neuromyelitis Optica Spectrum Disorder • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Complement C5 Inhibitor (Anti-C5) and Neonatal Fc Receptor Antagonist Anti-FcRn in Myasthenia Gravis at University Public Hospitals of Paris, France (AP-HP): What Is the Market Share of These New Treatments? (ISPOR-EU 2025) - "This falls to 352 DDD in 2023 with the arrival of ravulizumab, then goes to 1861 DDD in 2024 despite the eculizumab biosimilar. Prescriptions are tending towards efgartigimod-IV, though ravulizumab continues to hold an important place, particularly in long-stay patients, where it replaces eculizumab and generates the highest costs. However, this trend could change with the arrival of subcutaneous forms available in community pharmacies (zilucoplan, efgartigimod-SC and rozanolixizumab), potentially modifying therapeutic practices and hospital costs."

Clinical • CNS Disorders • Myasthenia Gravis

EXTRAPOLATION TO NEUROMYELITIS OPTICA SPECTRUM DISORDER (NMOSD) INDICATION FOR EPYSQLI®, SB12 (BIOSIMILAR TO REFERENCE ECULIZUMAB) (WCN 2025) - "The totality-of-the-evidence compared to ECU-RP and the scientific evidence from existing data on ECU-RP support the potential use of EPYSQLI® in NMOSD by principle of extrapolation."

CNS Disorders

Pharmacological Therapies in Paroxysmal Nocturnal Haemoglobinuria: Focus on Complement Inhibition. (PubMed, Drugs) - "This has been largely supplanted by a longer-acting antibody, ravulizumab, targeting the same binding site on C5...Other terminal inhibitors available include eculizumab biosimilars, crovalimab, pozelimab and cemdisiran (combination)...Currently available proximal inhibitors (and their targets) are pegcetacoplan (C3), danicopan (Factor D) and iptacopan (Factor B). While effective, as with all other complement inhibitors, there is a risk of breakthrough IVH with their use and approaches to manage this complication are being developed."

Journal • Review • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Thrombosis

LONG-TERM SAFETY OF SB12 IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: UP TO 2-YEAR EXTENSION TREATMENT SAFETY DATA (EHA 2025) - P3 | "Background: SB12 (EPYSQLITM) is a biosimilar to eculizumab reference product (ECU), developed for treating paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome in Europe. SB12 demonstrated long-term safety up to 158 weeks, consistent with the findings of the phase III study. No new safety signals were identified, and no fatal cases occurred throughout the entire treatment period, with all SAEs resolving completely."

Clinical • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Nephrology • Novel Coronavirus Disease • Paroxysmal Nocturnal Hemoglobinuria • Pneumonia • Rare Diseases • Respiratory Diseases

FEMALE GENDER IS PROBABLY ASSOCIATED WITH WORSE HEMATOLOGIC RESPONSE TO C5 INHIBITORS IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (EHA 2025) - "This study included 96 patients with PNH who received either an eculizumab biosimilar (Elizaria, n=83) or ravulizumab (Ultomiris, n=13). Female gender is likely associated with a worse hematologic response to C5 inhibitors, potentially due to a higher incidence of extravascular hemolysis. This observation may be speculatively explained by differences in immune system activity between males and females. A history of AA was also identified as a predictor of suboptimal response."

Anemia • Aplastic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Samsung Bioepis Presents Long-Term Safety Data of EPYSQLI (Eculizumab) in PNH at the European Hematology Association (EHA) Congress 2025 (Businesswire) - P3 | N=50 | NCT04058158 | Sponsor: Samsung Bioepis Co., Ltd. | "A total of 46 patients from the Phase 3 study received ET. During ET, seven patients (15.2%) experienced a total of 14 SAEs with no occurrence of fatal cases, and all patients fully recovered without permanently discontinuing the treatment. The exposure-adjusted event rate (EAER) was comparable between initial 52-week period and ET period (EAER were 0.13 and 0.17, respectively), and there was no statistically difference between initial 52-week and ET period in EAER (p-value = 0.76). The study is consistent with the findings of the Phase 3 study with no newly identified safety signals and no fatal cases occurred throughout the entire treatment period with all SAEs resolving completely."

P3 data • Paroxysmal Nocturnal Hemoglobinuria

A Cost Minimization and Budget Impact Analysis of an Eculizumab Biosimilar, ABP 959, From the Spanish Healthcare Perspective (ISPOR 2025) - "OBJECTIVES: To estimate the economic consequences of adopting ABP 959, an eculizumab biosimilar, for treating paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uremic syndrome (aHUS). The CMA and BIA both demonstrated substantial estimated cost savings with ABP 959 compared with originator eculizumab and ravulizumab. The savings in drug acquisition costs offset the higher administration costs from more frequent administrations of ABP 959 compared with ravulizumab. These results support the rapid adoption of ABP 959 in treating PNH and aHUS."

HEOR • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Paroxysmal Nocturnal Hemoglobinuria

Validation for soluble C5b-9 detection and comparative analysis of three quantification methods. (PubMed, J Immunol Methods) - "This study confirms that the Quidel sC5b-9 ELISA kit is a reliable tool for detecting complement activation and inhibition. However, the Hycult assay offers a broader dynamic range which can be an important consideration when assessing assay suitability for for disease monitoring and therapeutic assessments."

Journal

SB12, Biosimilar To Eculizumab (Complement 5 Inhibitor) For Generalized Myasthenia Gravis (P4-8.013). (PubMed, Neurology) - "Mr. KIM has received personal compensation for serving as an employee of Samsung Bioepis Co., Ltd.."

Clinical • Journal • Atypical Hemolytic Uremic Syndrome • CNS Disorders • Complement-mediated Rare Disorders • Hematological Disorders • Inflammation • Myasthenia Gravis • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Teva and Samsung Bioepis Announce Biosimilar EPYSQLI (eculizumab-aagh) Injection Now Available in the United States (GlobeNewswire) - "Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd...and Samsung Bioepis Co., Ltd. today announced the availability of EPYSQLI (eculizumab-aagh) in the U.S. EPYSQLI is a biosimilar to Soliris (eculizumab) for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS) and generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AchR) antibody positive. EPYSQLI will be offered at a 30% discount of the Wholesale Acquisition Cost (WAC) of the reference product, Soliris, offering one of the greatest cost-saving biosimilars to Soliris in the U.S."

Launch US • Atypical Hemolytic Uremic Syndrome • Myasthenia Gravis • Paroxysmal Nocturnal Hemoglobinuria

EPYSQLI (SB12; Biosimilar to Reference Eculizumab) in Asian and Non-Asian Patients With Paroxysmal Nocturnal Hemoglobinuria: Subgroup Analysis of a Global Phase III Randomized Controlled Trial. (PubMed, EJHaem) - "In addition, transfusion avoidance (68.1% for SB12 vs. 72.9% for ECU, p-value of 0.4492) and hemoglobin stabilization (SB12-ECU: 6.3%, 95% confidence interval [CI] [-21.5, 34.1] and SB12-ECU: 2.5%, 95% CI [-24.8, 29.8] using stringent criteria) as post-hoc endpoints were not substantially different between SB12 and ECU treatment groups in the overall population as well as in Asians and Non-Asians. In conclusion, this subgroup analysis by race (Asians and Non-Asians) supports comparable efficacy and safety between SB12 and reference eculizumab in global PNH patients including no difference in transfusion avoidance effect."

Clinical • Journal • P3 data • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

SB12, Biosimilar To Eculizumab (Complement 5 Inhibitor) For Generalized Myasthenia Gravis (AAN 2025) - "Comprehensive analytical and clinical studies of SB12 compared to ECU-RP support its use for gMG. Further clinical studies in gMG could provide valuable insight in the treatment."

Atypical Hemolytic Uremic Syndrome • CNS Disorders • Complement-mediated Rare Disorders • Hematological Disorders • Inflammation • Myasthenia Gravis • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

The Path to Accessible Care: Development and Impact of Eculizumab Biosimilars for Paroxysmal Nocturnal Hemoglobinuria and Atypical Hemolytic Uremic Syndrome. (PubMed, BioDrugs) - "Clinical use of biosimilars in Europe in the last 15 years has demonstrated that they are as safe and effective as their reference products, and can also drive cost reductions and increase patients' access to treatment. This review aims to increase awareness about the importance of biosimilars of reference eculizumab and their entry for use in patients with paroxysmal nocturnal hemoglobinuria or atypical hemolytic uremic syndrome based on the accumulated experience of other previously approved biosimilars, and to provide an overview of the stringent biosimilar development pathway in general and the concept of extrapolation in particular."

Journal • Review • Atypical Hemolytic Uremic Syndrome • Cardiovascular • CNS Disorders • Complement-mediated Rare Disorders • Hematological Disorders • Myasthenia Gravis • Nephrology • Neuromyelitis Optica Spectrum Disorder • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

Samsung Bioepis and Teva Enter into a Strategic Partnership for Commercialization of EPYSQLI (eculizumab-aagh) in the United States (GlobeNewswire) - "Samsung Bioepis Co., Ltd. and Teva Pharmaceutical Industries Ltd...announced today that the companies have entered into a license, development and commercialization agreement for EPYSQLI (eculizumab-aagh), Samsung Bioepis’ biosimilar to Soliris (eculizumab-aagh) in the United States (U.S.). Under the terms of the agreement, Samsung Bioepis will be responsible for the development, regulatory registration, manufacture and supply of the product, while Teva will be responsible for commercialization of the product in the U.S. The financial terms of the agreement remain confidential."

Licensing / partnership • Paroxysmal Nocturnal Hemoglobinuria

RESULTS OF LONG-TERM THERAPY WITH A BIOSIMILAR OF ECULIZUMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA. (PubMed, Acta Haematol) - "The study findings confirm the long-term efficacy and safety of biosimilar in patients with PNH."

Journal • Alopecia • Chronic Kidney Disease • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease

Totality of the evidence supports extrapolation of atypical hemolytic uremic syndrome (aHUS) Indication for EPYSQLI (biosimilar to reference eculizumab) (ESPN 2024) - "Aims/Purpose: EPYSQLI (SB12), a biosimilar to eculizumab reference product (ECU-RP), was approved by the European Medicines Agency in May 2023 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), for which a confirmatory Phase III study was conducted. EPYSQLI (SB12) is a biosimilar to ECU-RP based on the totality-of-the-evidence, demonstrating their analytical, pharmacology and clinical comparability, and supporting its extrapolation to reference product indications, such as aHUS."

Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Hematological Disorders • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Comparative clinical efficacy and safety of biosimilar ABP 959 and eculizumab reference product in patients with paroxysmal nocturnal hemoglobinuria. (PubMed, Am J Hematol) - P3 | "ABP 959 is a biosimilar to the eculizumab reference product (RP), which is approved for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH). The results of this study in patients with PNH, along with previously demonstrated similarity of analytical, nonclinical, and clinical pharmacokinetics and pharmacodynamics in healthy volunteers support a demonstration of no clinically meaningful differences between ABP 959 and eculizumab RP. Clinical Trial Registration: NCT03818607."

Clinical • Journal • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

FDA Approves Samsung Bioepis’ EPYSQLI (eculizumab-aagh) as a Biosimilar to Soliris (eculizumab) (GlobeNewswire) - "Samsung Bioepis Co., Ltd. announced today that the U.S. Food and Drug Administration (FDA) has approved the Biologics License Application (BLA) for EPYSQLI (eculizumab-aagh) as a biosimilar to Soliris (eculizumab). EPYSQLI has been approved for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy. EPYSQLI is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS)."

FDA approval • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria

TRANSFUSION AVOIDANCE WITH EPYSQLI™ (SB12), A BIOSIMILAR TO REFERENCE ECULIZUMAB: A POST-HOC ANALYSIS FROM THE PIVOTAL PHASE III STUDY. (EHA 2024) - "Transfusion avoidance by SB12 versus ECU treatments showed comparable results, although the small samplesize represents a limit to data interpretation. Overall, transfusion avoidance results support the previouslydemonstrated clinical efficacy of EPYSQLI (SB12), a biosimilar to reference eculizumab."

P3 data • Retrospective data • Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria

EVALUATION OF HEREDITARY FRUCTOSE TOLERANCE IN PREVALENT PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA, HEMOLYTIC UREMIC SYNDROME, OR MYASTHENIA GRAVIS (EHA 2024) - "Inclusion of sorbitol in ABP 959, an eculizumabbiosimilar, enhances the stability of ABP 959 when frozen, but may raise concern for patients with hereditaryfructose intolerance (HFI) who cannot metabolize sorbitol. By analyzing decades of patient medical records and claims data from the US, Germany and the UK, thelikelihood for a patient of having both HFI and eculizumab indicated conditions is very low. If HFI is suspected,a detailed symptom history should be collected prior to initiating treatment with biosimilar ABP 959."

Clinical • Atypical Hemolytic Uremic Syndrome • CNS Disorders • Complement-mediated Rare Disorders • Hematological Disorders • Myasthenia Gravis • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases