vemircopan (ALXN2050) / AstraZeneca - LARVOL DELTA

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

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

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

Targeting complement in IgA nephropathy. (PubMed, Clin Kidney J) - "Several ongoing trials are evaluating the efficacy of new agents against factor B (iptacopan, Ionis-FB-L), C3 (pegcetacoplan), factor D (vemircopan, pelecopan), C5 (ravulizumab, cemdisiran) and C5a receptor 1 (avacopan). In this study, we provide a comprehensive review of the role of complement in IgAN, including the emerging mechanisms of complement activation and the promising potential of complement inhibitors as a viable treatment option for IgAN."

Journal • Review • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease

221: RestoreD: A clinical trial with oral ALXN2050 – a Complement Factor D inhibitor - for Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (lgAN) (ACR Convergence 2023) - "Non-CME"

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

ALXN2050-MG-201: Study of ALXN2050 in Adult Participants With Generalized Myasthenia Gravis (clinicaltrials.gov) - P2 | N=70 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Myasthenia Gravis • CFB

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

New P1 trial

ALXN2050-MG-201: Study of ALXN2050 in Adult Participants With Generalized Myasthenia Gravis (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: Alexion | Trial completion date: Sep 2025 ➔ Dec 2025 | Trial primary completion date: Jun 2023 ➔ Nov 2023

Trial completion date • Trial primary completion date • CNS Disorders • Myasthenia Gravis • CFB

Study of ALXN2050 in Participants With Hepatic Impairment (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Alexion | Trial completion date: Oct 2023 ➔ Oct 2024 | Trial primary completion date: May 2023 ➔ Apr 2024

Trial completion date • Trial primary completion date • Hepatology

Vemircopan (ALXN2050) monotherapy in paroxysmal nocturnal haemoglobinuria: Interim data from phase 2 Open-Label Proof-of-Concept study (BSH 2023) - P2 | "No new safety signals were identified during the 12-week period. This analysis provides proof of concept of vemircopan in PNH and suggests that phase 3 trials are warranted."

Clinical • Monotherapy • P2 data • Anemia • Cardiovascular • CNS Disorders • Complement-mediated Rare Disorders • Epilepsy • Fatigue • Hematological Disorders • Infectious Disease • Meningococcal Infections • Pain • Paroxysmal Nocturnal Hemoglobinuria • Thrombosis

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=30 | Recruiting | Sponsor: Alexion | Not yet recruiting ➔ Recruiting

Enrollment open

A PHASE 2 STUDY EVALUATING THE EFFICACY AND SAFETY OF ALXN2050, A COMPLEMENT FACTOR D INHIBITOR, IN IMMUNOGLOBULIN A NEPHROPATHY OR PROLIFERATIVE LUPUS NEPHRITIS (LN) (ISN-WCN 2023) - P2 | "View Large Image Figure Viewer Download Hi-res image Download (PPT) Results The study design incorporates 3:1:3 randomization in favor of the study drug arm, continued administration of standard of care medications in all treatment groups, placebo crossover to treatment for IgA nephropathy, and potential use of rescue therapy for renal flare for LN. Conclusions This abstract was also submitted to American Society of Nephrology (ASN) Annual Meeting 2022."

Clinical • P2 data • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease

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=30 | Not yet recruiting | Sponsor: Alexion

New P1 trial