BMN 331 / BioMarin - LARVOL DELTA

Status of Current Clinical Trials on Therapy for Hereditary Angioedema (IMMUNOLOGY 2026) - "The sole drug in phase 4 is CSL312 (Garadacimab), a fully human IgG4 monoclonal antibody targeting activated factor XIIa. Drugs in phase 3 include: NTLA-2002, a single-dose intravenous gene therapy targeting inactivation of the KLKB1 gene; Navenibart, an IgG1 monoclonal antibody inhibiting activated kallikrein; OCTA-C1-INH, a virus-inactivated, nanofiltrated, highly purified concentrate of C1-INH derived from pooled human plasma; ADX-324, an siRNA therapy to reduce hepatic production of prekallikrein (PKK); Donidalorsen, an antisense oligonucleotide targeted against hepatic PKK mRNA; Sebetralstat and berotralstat, both plasma kallikrein inhibitors that reduce production of bradykinin; and deucrictibant, a competitive bradykinin B2 receptor antagonist. Advances in gene therapy, biologics, RNA interference therapeutics, and improved replacement strategies hold promise for transforming both rescue and prophylactic management for HAE. Ongoing evaluation of safety,..."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Gene Therapies • Hereditary Angioedema • AVEN

HAErmony-1: A Gene Therapy Study of BMN 331 in Subjects With Hereditary Angioedema (clinicaltrials.gov) - P1/2 | N=44 | Active, not recruiting | Sponsor: BioMarin Pharmaceutical | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene therapy • Cardiovascular • Complement-mediated Rare Disorders • Gene Therapies • Hereditary Angioedema

Clinical Progress in Hepatic Targeting for Novel Prophylactic Therapies in Hereditary Angioedema. (PubMed, J Allergy Clin Immunol Pract) - "Donidalorsen is an investigational GalNAc-conjugated antisense oligonucleotide that binds to prekallikrein mRNA in the liver and reduces the expression of prekallikrein...ADX-324 is a GalNAc-conjugated siRNA being investigated in HAE...NTLA-2002 is an investigational in vivo clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based therapy designed to knock out the prekallikrein-coding KLKB1 gene in hepatocytes; a phase 1/2 study is ongoing. Findings from these and other ongoing studies are highly anticipated with the expectation of expanding the array of treatment options in HAE."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Gene Therapies • Hereditary Angioedema

HAErmony-1: A Gene Therapy Study of BMN 331 in Subjects With Hereditary Angioedema (clinicaltrials.gov) - P1/2 | N=34 | Recruiting | Sponsor: BioMarin Pharmaceutical | Initiation date: Nov 2021 ➔ Feb 2022

Trial initiation date • Cardiovascular • Complement-mediated Rare Disorders • Gene Therapies • Hereditary Angioedema

HAErmony-1: A Gene Therapy Study of BMN 331 in Subjects With Hereditary Angioedema (clinicaltrials.gov) - P1/2; N=34; Recruiting; Sponsor: BioMarin Pharmaceutical; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Cardiovascular • Complement-mediated Rare Disorders • Gene Therapies • Hereditary Angioedema

HAErmony-1: A Phase 1/2 Safety, Tolerability & Efficacy Gene Therapy Study of BMN 331 in Subjects With Hereditary Angioedema (clinicaltrials.gov) - P1/2; N=34; Not yet recruiting; Sponsor: BioMarin Pharmaceutical

Clinical • New P1/2 trial • Cardiovascular • Complement-mediated Rare Disorders • Gene Therapies • Hereditary Angioedema