orilanolimab IV (ALXN1830 IV) / AstraZeneca - LARVOL DELTA

SYNT001: A Humanized IgG4 Monoclonal Antibody That Disrupts the Interaction of FcRn and IgG for the Treatment of IgG-Mediated Autoimmune Diseases (ASH 2017) - P1b; "SYNT001 was well tolerated and produced rapid, durable, and clinically significant reductions in all IgG subclasses and CIC in healthy volunteers. Both the level and duration of the pharmacodynamic effect provide strong support for the potential efficacy of SYNT001 as a therapeutic agent in the treatment of IgG-mediated autoimmune diseases such as WAIHA. Accordingly, a phase 1b study of SYNT001 in WAIHA patients is underway (www.clinicaltrials.gov ID: NCT03075878)."

Clinical • Biosimilar • Complement-mediated Rare Disorders • Hematological Malignancies • Immunology

Safety, Tolerability, and Activity of ALXN1830 Targeting the Neonatal Fc Receptor in Chronic Pemphigus. (PubMed, J Invest Dermatol) - P1b/2 | "ALXN1830 was well tolerated with headache as the most common adverse event. This study reveals the importance of FcRn in the biology of pemphigus and potential for use of ALXN1830 in pemphigus treatment."

Clinical • Journal • Complement-mediated Rare Disorders • Dermatopathology • Immunology • Pain • Pemphigus Vulgaris • CRP

ALXN1830 in Patients With Warm Autoimmune Hemolytic Anemia (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: Alexion Pharmaceuticals; N=32 ➔ 0; Suspended ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology

Blocking FcRn in humans reduces circulating IgG levels and inhibits IgG immune complex-mediated immune responses. (PubMed, Sci Adv) - "In addition, IgG IC induction of inflammatory pathways was dependent on FcRn and inhibited by SYNT001. These studies expand the role of FcRn in humans by showing that it controls not only IgG protection from catabolism but also inflammatory pathways associated with IgG ICs involved in a variety of autoimmune diseases."

Journal • Immunology

FcRn blockade with SYNT001 for the treatment of pemphigus (IID 2018) - P1b; "These interim data show SYNT001 is well tolerated in PV and PF. This first-in-human study in pemphigus provides initial proof-of-concept for anti-FcRn treatment with SYNT001 in this disorder."

Biosimilar • CNS Disorders • Complement-mediated Rare Disorders • Dermatology • Immunology • Pain • Rare Diseases

ALXN1830 in Patients With Warm Autoimmune Hemolytic Anemia (clinicaltrials.gov) - P2; N=32; Suspended; Sponsor: Alexion Pharmaceuticals; Trial completion date: Dec 2021 ➔ Apr 2023; Initiation date: Feb 2020 ➔ Jul 2021; Not yet recruiting ➔ Suspended; Trial primary completion date: Jun 2021 ➔ Oct 2022

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Trial suspension • Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Rare Diseases

ALXN1830 in Patients with Warm Autoimmune Hemolytic Anemia ALXN1830 en pacientes con anemia hemolítica autoinmunitaria por anticuerpos calientes (clinicaltrialsregister.eu) - P2; N=32; Ongoing; Sponsor: Alexion Pharmaceuticals, Inc.

Clinical • New P2 trial • Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Rare Diseases • HP

ALXN1830 in Patients With Warm Autoimmune Hemolytic Anemia (clinicaltrials.gov) - P2; N=32; Not yet recruiting; Sponsor: Alexion Pharmaceuticals

Clinical • New P2 trial

Next-generation Fc receptor-targeting biologics for autoimmune diseases. (PubMed, Autoimmun Rev) - "These include PF-06755347 (GL-2045), CSL730 (M230), CSL777 and Pan Fc Receptor Interacting Molecule (PRIM). Neonatal Fc receptor (FcRn)-targeting therapeutics block the FcRn receptor and are represented by candidate drugs such as the Fc fragment efgartigimod and the monoclonal antibodies rozanolixizumab (UCB7665), M281 and SYNT001. Finally, Fc and FcγR-targeting therapeutics, comprise molecules that target the Fc of IgG, such as the recombinant soluble FcγIIb receptor valziflocept (SM101/SHP652) and various monoclonal antibodies directed against the receptors...Although initial results are promising, further long-term data and a better understanding of the unique mechanisms of action of the different molecules are needed. The efficacy, safety, convenience of administration, duration of effects, and cost will all contribute to determining which of the molecules will be successful in the clinic."

Journal • Review

A Safety and Dose-Finding Study of SYNT001 in Subjects With Pemphigus (Vulgaris or Foliaceus) (clinicaltrials.gov) - P1b/2; N=8; Terminated; Sponsor: Alexion Pharmaceuticals; N=16 ➔ 8; Recruiting ➔ Terminated; Study objectives achieved

Clinical • Enrollment change • Trial termination

A Safety Study of SYNT001 in Subjects With Warm Autoimmune Hemolytic Anemia (WAIHA) (clinicaltrials.gov) - P1b/2; N=8; Terminated; Sponsor: Alexion Pharmaceuticals; Phase classification: P1b ➔ P1b/2; N=16 ➔ 8; Trial completion date: Jan 2019 ➔ Aug 2019; Recruiting ➔ Terminated; Trial primary completion date: Jan 2019 ➔ Aug 2019; Focus resources on a planned phase 2/3 study

Clinical • Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Trial termination