vemircopan (ALXN2050) / AstraZeneca - LARVOL DELTA

Efficacy and Safety of Vemircopan in Generalized Myasthenia Gravis: A Randomized Clinical Trial. (PubMed, JAMA Neurol) - P2 | "In this double-blind, parallel-group, placebo-controlled phase 2 randomized clinical trial, vemircopan did not meet the prespecified threshold for efficacy, and consequently, the study was terminated. ClinicalTrials.gov Identifier: NCT05218096."

Clinical • Journal • CNS Disorders • Fatigue • Hepatology • Herpes Simplex • Infectious Disease • Liver Failure • Meningococcal Infections • Myasthenia Gravis

New Anticomplement Drugs in Nephrology - Mechanism and Indication. (PubMed, Kidney Blood Press Res) - "Anticomplement therapies represent a transformative advance in nephrology, offering targeted interventions that can improve outcomes for patients with complement-mediated kidney diseases. Their strategic use may reduce disease progression, manage inflammation, and mitigate organ damage, highlighting the potential of personalized treatment approaches in complement-driven renal disorders."

Journal • Review • ANCA Vasculitis • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Diabetic Nephropathy • Fibrosis • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Nephrology • Renal Disease • Systemic Lupus Erythematosus • Vasculitis

HEPATIC EXPRESSION OF MATURE-FACTOR D CAUSES C3-DEPENDENT FACTOR B DEPLETION WITH THERAPEUTIC POTENTIAL FOR COMPLEMENT MEDIATED DISEASE IN MICE (ISN-WCN 2026) - "Vemircopan was able to prevent FB depletion, unlike FD monoclonal antibody.Finally, the depletion of FB by AAV8/mature FD effectively prevented the development of disease in murine models of atypical hemolytic uremic syndrome and C3 glomerulopathy.Conclusion Our data suggest that the regulation of FD by MASP3 and the segregated biosynthesis of FD, FB and C3 have physiological significance. The ectopic expression of mature FD in the liver causes C3-dependent FB depletion, a phenomenon that could be exploited for the treatment of complement-mediated AP diseases."

Preclinical • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Developmental Disorders • Glomerulonephritis • PRSS3

Maternal and fetal pharmacokinetics (PK) of pegcetacoplan in paroxysmal nocturnal hemoglobinuria (PNH): A case report of use in pregnancy (ASH 2025) - "Aftertrials of vemircopan and iptacopan, she was transitioned to pegcetacoplan 1080 mg subcutaneous2x/week and achieved transfusion independence (hemoglobin ~110 g/L)...Thesefindings are consistent with preclinical non-human animal data and pegcetacoplan's physicochemicalproperties—a large, pegylated, and hydrophilic cyclic peptide, expected to have limited membranepermeability.In a patient with hemolytic PNH and inadequate hematologic response to eculizumab, conception onpegcetacoplan was not associated with adverse fetal/pregnancy outcomes, and third-trimesterreinitiation resulted in rapid hematologic improvement, transfusion independence, and anuncomplicated peripartum course.In conclusion, this report provides the first clinical and PK evidence suggesting that third-trimester use ofpegcetacoplan may be a viable treatment option in select pregnant patients with PNH with suboptimalresponse to C5 inhibitors. Following reinitiation of pegcetacoplan at 28 weeks GA,..."

Case report • Clinical • PK/PD data • Cardiovascular • Complement-mediated Rare Disorders • Diabetes • Genetic Disorders • Gestational Diabetes • Obesity • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

Efficacy and Safety of ALXN2050 in IgAN: Results of a Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial (KIDNEY WEEK 2025) - P2 | "Conclusion A non-statistically significant reduction in UP was observed with ALXN2050 180mg vs PBO. While ALXN2050 was generally well-tolerated in IgAN, a risk of liver enzyme elevation was identified from study-wide data review."

Clinical • P2 data • Glomerulonephritis • Hepatology • IgA Nephropathy • Immunology • Inflammatory Arthritis • Liver Failure • Lupus • Lupus Nephritis • Nephrology • Rare Diseases • Renal Disease

Efficacy and Safety of ALXN2050 (Vemircopan) in Lupus Nephritis: Results of a Phase 2 Trial (KIDNEY WEEK 2025) - P2 | "Conclusion There was no statistically significant difference in proteinuria reduction with ALXN2050 vs PBO. Liver enzyme elevation was determined to be an identified risk with ALXN2050 after study-wide data review."

Clinical • P2 data • Glomerulonephritis • Hepatology • IgA Nephropathy • Immunology • Inflammatory Arthritis • Liver Failure • Lupus • Lupus Nephritis • Nephrology • Rare Diseases • Renal Disease

Iptacopan Treatment Improves Clinical Parameters in a Real-World Cohort with Paroxysmal Nocturnal Hemoglobinuria: Evidence from a Managed Access Program (ASH 2024) - "Overall, 5 (14.3%) patients were complement treatment-naïve, and 30 (85.7%) patients were reported to receive ≥1 prior complement inhibitor therapies including eculizumab (23 [65.7%]), ravulizumab (15 [42.9%]), pegcetacoplan (7 [20.0%]), vemircopan (6 [17.1%]), and others. At the time of iptacopan retreatment request, a higher proportion of patients reported near normal Hb levels and reticulocyte count, had a reduced number of transfusion visits, and improved fatigue and treatment satisfaction. Additional long-term results may provide better understanding of iptacopan safety and efficacy in real-world patients with PNH."

Clinical • Real-world • Real-world evidence • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

Efficacy and Safety of Vemircopan as Monotherapy in Patients With Paroxysmal Nocturnal Hemoglobinuria. (PubMed, Blood Adv) - P2 | "Adults (≥18 years) with PNH who were treatment-naive, switched from eculizumab with hemoglobin (Hgb) <10 g/dL, or rolled over from danicopan monotherapy (ACH471-103 trial; NCT03181633) were enrolled. This trial evaluating vemircopan monotherapy in patients with PNH met its primary efficacy endpoint; however, concerns regarding BT-IVH risk and suboptimal, inconsistent control of IVH emerged, leading to early trial termination. This trial was registered with ClinicalTrials.gov (NCT04170023) and EudraCT (2019-003830-17)."

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

First-in-Class Clinically Investigated Oral Factor D Inhibitors for the Treatment of Complement-Mediated Diseases. (PubMed, Pharm Res) - "Preclinical evaluations of danicopan and vermicopan provided rationales to conduct clinical studies in complement-mediated diseases. Recently, danicopan was approved as an add-on therapy to the C5 inhibitors ravulizumab or eculizumab for the treatment of extravascular hemolysis in patients with PNH."

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

The Role of Complement in the Pathogenesis and Treatment of Myasthenia Gravis. (PubMed, Cells) - "This has led to the development of the first C5 inhibitors approved for myasthenia gravis with AchR antibodies: eculizumab, ravulizumab, and zilucoplan. Other clinical trials are currently in progress, investigating the potential therapeutic role of other targets, including the Factor B inhibition or hepatic synthesis of the C5 protein. Other proposed potential targets that have not yet been clinically tested are also discussed in this review article."

Journal • Review • CNS Disorders • Immunology • Myasthenia Gravis

Study of ALXN2050 in Participants With Hepatic Impairment (clinicaltrials.gov) - P1 | N=26 | Terminated | Sponsor: Alexion Pharmaceuticals, Inc. | Trial completion date: May 2025 ➔ Aug 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: May 2025 ➔ Aug 2024; Sponsor decision.

Trial completion date • Trial primary completion date • Trial termination • Hepatology

AstraZeneca CEO defends 'fantastic' Alexion buyout in face of $753M hit from dropped drug (FierceBiotech) - "Buying Alexion remains a 'fantastic acquisition' for AstraZeneca, the Big Pharma’s CEO has said, even as the company takes a $753 million hit for abandoning one of the drugs from that acquisition...The drug in question, vemircopan, was once a hot prospect at AstraZeneca...the abandonment of other Alexion drugs in the form of ALXN1840 for Wilson disease and ALXN1820 for sickle cell disease...The drugmaker said....in its fourth-quarter clinical trials update that it stopped the studies because of a lack of efficacy. AstraZeneca used slightly different language when disclosing the broader termination of the program, attributing the decision to phase 2 safety and efficacy data."

Discontinued • Trial status • Genetic Disorders • IgA Nephropathy • Lupus Nephritis • Sickle Cell Disease

Study of ALXN2050 in Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN) (clinicaltrials.gov) - P2 | N=102 | Terminated | Sponsor: Alexion Pharmaceuticals, Inc. | Trial completion date: Jun 2026 ➔ Dec 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jun 2026 ➔ Dec 2024; Sponsor Decision.

Trial completion date • Trial primary completion date • Trial termination • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease

Study of ALXN2050 in Participants With Hepatic Impairment (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Trial completion date: Oct 2024 ➔ May 2025 | Trial primary completion date: Oct 2024 ➔ May 2025

Trial completion date • Trial primary completion date • Hepatology

Study of ALXN2050 in Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN) (clinicaltrials.gov) - P2 | N=126 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting | N=70 ➔ 126

Enrollment change • Enrollment closed • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease

Study of ALXN2050 in Participants With Hepatic Impairment (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology

Study of ALXN2050 in Participants With Hepatic Impairment (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Trial primary completion date: Apr 2024 ➔ Sep 2024

Trial primary completion date • Hepatology

Study of the Oral Factor D (FD) Inhibitor ALXN2050 in PNH Patients as Monotherapy (clinicaltrials.gov) - P2 | N=29 | Terminated | Sponsor: Alexion Pharmaceuticals, Inc. | Trial completion date: Oct 2026 ➔ Mar 2024 | Active, not recruiting ➔ Terminated; Did not appropriately control IVH; significantly increased rates of BTH and LDH excursions (LDH excursions is defined by LDH values > X2ULN) compared to ravulizumab.

Monotherapy • Trial completion date • Trial termination • Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

A Study to Investigate the Pharmacokinetic Profile of ALXN2050 Modified Release Prototype Formulations and Immediate Release Reference Tablet in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=80 | Completed | Sponsor: Alexion Pharmaceuticals, Inc. | Recruiting ➔ Completed | N=30 ➔ 80

Enrollment change • Trial completion

Potential Drug Interaction Study Between Vemircopan and Rosuvastatin, Metformin, Levonorgestrel/Ethinyl Estradiol-containing Oral Contraceptives, and Carbamazepine (clinicaltrials.gov) - P1 | N=60 | Completed | Sponsor: Alexion Pharmaceuticals, Inc. | Recruiting ➔ Completed

Trial completion

ALXN2050-MG-201: Study of ALXN2050 in Adult Participants With Generalized Myasthenia Gravis (clinicaltrials.gov) - P2 | N=70 | Terminated | Sponsor: Alexion Pharmaceuticals, Inc. | Trial completion date: Dec 2025 ➔ Apr 2024 | Active, not recruiting ➔ Terminated; Sponsor decision

Trial completion date • Trial termination • CNS Disorders • Myasthenia Gravis

Study of ALXN2050 in Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN) (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | N=126 ➔ 70

Enrollment change • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease

Potential Drug Interaction Study Between Vemircopan and Rosuvastatin, Metformin, Levonorgestrel/Ethinyl Estradiol-containing Oral Contraceptives, and Carbamazepine (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Initiation date: Oct 2023 ➔ Jan 2024

Trial initiation date

Study of ALXN2050 in Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN) (clinicaltrials.gov) - P2 | N=126 | Recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Trial primary completion date: Jan 2024 ➔ Jun 2026

Trial primary completion date • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease

Potential Drug Interaction Study Between Vemircopan and Rosuvastatin, Metformin, Levonorgestrel/Ethinyl Estradiol-containing Oral Contraceptives, and Carbamazepine (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open