navenibart (STAR-0215) / Kaken Pharma, BioCryst Pharmaceuticals - LARVOL DELTA

Current and future therapies for bradykinin-mediated angioedema (PubMed, Dermatologie (Heidelb)) - "On-demand treatment options include plasma-derived and recombinant C1 inhibitor (C1INH) concentrates, the bradykinin B2 receptor antagonist icatibant, and, more recently, the first orally available plasma kallikrein inhibitor, sebetralstat...LTP therapies include subcutaneous and intravenous C1INH preparations, the oral kallikrein inhibitor berotralstat, the anti-kallikrein monoclonal antibody lanadelumab, the factor XIIa inhibitor garadacimab, and the antisense oligonucleotide donidalorsen. Currently under development are the oral bradykinin B2 receptor antagonist deucrictibant, which is intended for both on-demand treatment and long-term prophylaxis in different formulations, long-acting antibodies, such as navenibart, and CRISPR/Cas9-based gene-editing therapies, such as NTLA-2002 with potential functional curative properties. In particular, orally available and long-acting therapies are expected to improve adherence, self-management, and quality of life in..."

Journal • Review • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

ALPHA-ORBIT: A Study of Navenibart in Participants With Hereditary Angioedema (clinicaltrials.gov) - P3 | N=157 | Active, not recruiting | Sponsor: Astria Therapeutics, Inc. | Enrolling by invitation ➔ Active, not recruiting | Trial completion date: Sep 2027 ➔ Jun 2027 | Trial primary completion date: Mar 2027 ➔ Dec 2026

Enrollment closed • Trial completion date • Trial primary completion date • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

A Trial to Compare the Pharmacokinetics of Two Presentations of Navenibart in Healthy Participants (clinicaltrials.gov) - P1 | N=180 | Recruiting | Sponsor: Astria Therapeutics, Inc.

New P1 trial

ALPHA-ORBIT: A Study of Navenibart in Participants With Hereditary Angioedema (clinicaltrials.gov) - P3 | N=145 | Enrolling by invitation | Sponsor: Astria Therapeutics, Inc. | Recruiting ➔ Enrolling by invitation

Enrollment status • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

A Long-Term Study of Navenibart in Participants With Hereditary Angioedema (clinicaltrials.gov) - P3 | N=145 | Enrolling by invitation | Sponsor: Astria Therapeutics, Inc.

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

Monoclonal antibodies in the management of hereditary angioedema. (PubMed, Expert Opin Biol Ther) - "This review focuses on the evaluation of three monoclonal antibodies developed for LTP of HAE, namely lanadelumab (Takhzyro®), garadacimab (Andembry®), and navenibart, in this order. The transition from older non-targeted LTP options to the use of monoclonal antibody-based therapies has fundamentally changed the treatment landscape by offering a safe, effective, and highly targeted solution. Although having different pharmacological characteristics, these LTP options share the same objective: to achieve complete disease control."

Journal • Review • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

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

STAR-0215-302: A Long-term Study of Navenibart in Participants with Hereditary Angioedema (clinicaltrialsregister.eu) - P2/3 | N=53 | Not yet recruiting | Sponsor: Astria Therapeutics Inc.

New P2/3 trial • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

An Open-Label Phase 1b/2 Trial of Navenibart, a Long-Acting Plasma Kallikrein Inhibitor for Hereditary Angioedema. (PubMed, J Allergy Clin Immunol) - "Navenibart was well tolerated and substantially reduced hereditary angioedema attacks, providing support for every-3-month and every-6-month administration of navenibart to prevent hereditary angioedema attacks."

Journal • P1/2 data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Infectious Disease • Nephrology • Pain

Navenibart Demonstrates Durable Efficacy and Tolerability Across Biological Sexes: Subgroup Analysis from the ALPHA-STAR Trial (AAAAI 2026) - P1/2 | "Conclusions Navenibart demonstrated consistent and durable efficacy with a favorable safety profile regardless of biological sex. These findings support the continued evaluation of navenibart (every 3- and 6-month) in a Phase 3 trial (ALPHA-ORBIT, NCT068428)."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

New Submission (AAAAI 2026) - P3 | "Conclusions Navenibart demonstrated favorable long-term safety and durable efficacy for up to 24 months to date in this trial. Q3M and Q6M regimens maintained robust disease control, validating ongoing evaluation in the Phase 3 ALPHA-ORBIT trial (NCT06842823)."

Late-breaking abstract • Breast Cancer • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Infectious Disease • Musculoskeletal Pain • Nephrology • Solid Tumor

Navenibart Delays Time to First Attack in Hereditary Angioedema: Results from ALPHA-STAR (AAAAI 2026) - P1/2 | "Median time to first attack in each cohort was: 450 mg, 109/171 days observed; 600/300 mg, 241/258 days observed; 600/600 mg, not estimable (7/12 participants had no HAE attack during treatment period). Conclusions The time to first attack data support the efficacy of navenibart in the reduction of HAE attacks and the continued investigation of every 3- and 6-month regimens in the Phase 3 trial (ALPHA-ORBIT, NCT068428)."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

"Emerging role of plasma kallikrein inhibitors in preventing hereditary angioedema flares in pregnancy". (PubMed, Ann Med Surg (Lond)) - "This article examines the emerging role of plasma kallikrein inhibitors in HAE prophylaxis during pregnancy, discusses the pharmacologic profile and potential advantages of Navenibart, and proposes cautious, preliminary clinical considerations within a shared decision-making framework. Multidisciplinary care and further research are urgently needed to establish safety and define the place of these agents in obstetric HAE management."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Obstetrics

Final Results From ALPHA-STAR A Phase 1b/2 Trial Of Navenibart In Hereditary Angioedema (ACAAI 2025) - P1/2 | "Conclusion Navenibart robustly and durably decreased the HAE attack rate with a favorable safety profile. Every 3- and 6-month regimens are currently being investigated in a Phase 3 trial (ALPHA-ORBIT, NCT068428)."

Clinical • P1/2 data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

A Long-Term Study of Navenibart in Participants With Hereditary Angioedema (clinicaltrials.gov) - P3 | N=145 | Enrolling by invitation | Sponsor: Astria Therapeutics, Inc.

New P3 trial • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Astria Therapeutics Now Enrolling HAE Patients in the European Union for the Phase 3 ALPHA-ORBIT Trial (Businesswire) - "Astria is enrolling the ongoing ALPHA-ORBIT trial with clinical trial sites open and accepting HAE patients across the United States, Europe, United Kingdom, Canada, Hong Kong, South Africa, Japan, North Macedonia, and Israel."

Trial status • Hereditary Angioedema

A Long-term Study of STAR-0215 in Participants With Hereditary Angioedema (clinicaltrials.gov) - P2 | N=56 | Active, not recruiting | Sponsor: Astria Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Astria Therapeutics Announces Publication of Navenibart Phase 1a Healthy Subject Results in the Annals of Allergy, Asthma & Immunology (Businesswire) - P1a | N=41 | NCT05477160 | Sponsor: Astria Therapeutics, Inc. | "Astria Therapeutics, Inc...announced that results from a Phase 1a trial in healthy subjects supporting navenibart’s potential to provide long-acting, safe, and effective attack prevention for hereditary angioedema (HAE) with dosing every 3 and 6 months have been published in the Annals of Allergy, Asthma & Immunology....Overview of results from the Phase 1a trial of navenibart in healthy subjects: For all doses ≥300 mg, navenibart mean half-life ranged from 82 to 105 days, supporting the potential for administration every 3 and 6 months. Navenibart’s inhibition of plasma kallikrein activity versus placebo was statistically significant (P<0.05); Navenibart was well-tolerated, with similar rates of adverse events between navenibart and placebo, and no serious adverse events were observed; Results demonstrated early proof of concept for navenibart as a potential long-acting therapy for HAE."

P1 data • Hereditary Angioedema

ALPHA-STAR: A Study of STAR-0215 in Participants With Hereditary Angioedema (clinicaltrials.gov) - P1/2 | N=29 | Completed | Sponsor: Astria Therapeutics, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Sep 2025 ➔ Mar 2025 | Trial primary completion date: Sep 2025 ➔ Mar 2025

Trial completion • Trial completion date • Trial primary completion date • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Safety and Pharmacokinetics of Long-Acting Plasma Kallikrein Inhibitor Navenibart (STAR-0215) in Healthy Adults. (PubMed, Ann Allergy Asthma Immunol) - "In this first-in-human study, up to 1200 mg of navenibart was well tolerated and demonstrated an extended half-life with durable plasma kallikrein inhibition."

Journal • PK/PD data • Cardiovascular • Complement-mediated Rare Disorders • Dermatology • Hereditary Angioedema

ALPHA-ORBIT: A Study of Navenibart in Participants with Hereditary Angioedema (clinicaltrials.gov) - P3 | N=145 | Recruiting | Sponsor: Astria Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Astria Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides a Corporate Update (Businesswire) - "Navenibart (STAR-0215): All of the 16 target enrollment patients from ALPHA-STAR have entered the ALPHA-SOLAR long-term open-label trial. Initial safety and efficacy data from ALPHA-SOLAR, with Q3M and Q6M administration, are expected mid-2025."

P2 data • Hereditary Angioedema

ALPHA-ORBIT: A Study of Navenibart in Participants with Hereditary Angioedema (clinicaltrials.gov) - P3 | N=145 | Not yet recruiting | Sponsor: Astria Therapeutics, Inc.

New P3 trial • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Astria Therapeutics Initiates ALPHA-ORBIT Phase 3 Pivotal Trial of Navenibart in Hereditary Angioedema (Businesswire) - "Astria Therapeutics, Inc...today announced the initiation of the ALPHA-ORBIT Phase 3 clinical trial of navenibart in people living with hereditary angioedema (HAE). Navenibart has the potential to provide rapid and sustained HAE attack prevention with a very low treatment burden and administration every 3 months (Q3M) and every 6 months (Q6M)...Top-line results from the trial are anticipated in early 2027."

P3 data: top line • Trial status • Hereditary Angioedema

Astria Therapeutics to Present at Upcoming American Academy of Allergy, Asthma and Immunology and World Allergy Organization Joint Congress (Businesswire) - "Astria Therapeutics, Inc...today announced that it will present three posters at the American Academy of Allergy, Asthma and Immunology (AAAAI) and World Allergy Organization (WAO) Joint Congress in San Diego, California on March 2, 2025."

Clinical protocol • P1/2 data • Preclinical • Atopic Dermatitis • Hereditary Angioedema