verducatib (BI 1291583) / Boehringer Ingelheim - LARVOL DELTA

Phase III AIRTIVITY study design: verducatib (BI 1291583) in people with bronchiectasis. (PubMed, ERJ Open Res) - P3 | "All pulmonary exacerbations are adjudicated. If the efficacy of verducatib is demonstrated and there is a favourable benefit-risk ratio, the AIRTIVITY results will provide confirmatory evidence for the use of verducatib 2.5 mg in a large and broad bronchiectasis population, independent of underlying aetiology."

Journal • P3 data • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CTSC

A Study in Healthy Men to Test Whether Carbamazepine Influences the Amount of Verducatib in the Blood (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open

Impact of the dipeptidyl peptidase 1 (DPP1) inhibitor verducatib on severe pulmonary exacerbations (PExs) in bronchiectasis: Pooled Phase 2 results from AIRLEAF® and CLAIRLEAF® (ERS 2026) - "1Chalmers JD et al. Eur Respir J 2025; 65:2401551"

P2 data • Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study in Healthy People to Measure How Different Doses of Verducatib Affect the Heart (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Test How Verducatib is Taken up in the Body of Healthy Chinese Participants (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion

A Study in Healthy Men to Test Whether Carbamazepine Influences the Amount of Verducatib in the Blood (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P1 trial

A Study in Healthy People to Measure How Different Doses of Verducatib Affect the Heart (clinicaltrials.gov) - P1 | N=56 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P1 trial

The AIRTIVITY Study: A Study to Find Out Whether BI 1291583 Helps People With Bronchiectasis (clinicaltrials.gov) - P3 | N=1755 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Oct 2028 ➔ Dec 2027 | Trial primary completion date: Sep 2028 ➔ Jun 2027

Trial completion date • Trial primary completion date • Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study to Test How BI 1291583 is Taken up in the Blood of People With and Without Liver Problems (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Sep 2026 ➔ Dec 2026 | Trial primary completion date: Sep 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Hepatology

The AIRTIVITY® Study: A Study to Find Out Whether BI 1291583 Helps People With Bronchiectasis (clinicaltrials.gov) - P3 | N=1680 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open • Bronchiectasis • Pulmonary Disease • Respiratory Diseases

The AIRTIVITY™ Study: A Study to Find Out Whether BI 1291583 Helps People With Bronchiectasis (clinicaltrials.gov) - P3 | N=1755 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Oct 2028 ➔ Aug 2027 | Trial primary completion date: Sep 2028 ➔ Jul 2027

Trial completion date • Trial primary completion date • Bronchiectasis • Pulmonary Disease • Respiratory Diseases

The AIRTIVITY® Study: A Study to Find Out Whether BI 1291583 Helps People With Bronchiectasis (clinicaltrials.gov) - P3 | N=1680 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P3 trial • Bronchiectasis • Pulmonary Disease • Respiratory Diseases

The AIRTIVITY™ Study: A Study to Find Out Whether BI 1291583 Helps People With Bronchiectasis (clinicaltrials.gov) - P3 | N=1755 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Aug 2027 ➔ Oct 2028 | Trial primary completion date: Jul 2027 ➔ Sep 2028

Trial completion date • Trial primary completion date • Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study to Test How Verducatib is Taken up in the Body of Healthy Chinese Participants (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Active, not recruiting

Enrollment closed

Final pooled data from Phase II studies (AIRLEAF®, CLAIRLEAF®) of the dipeptidyl peptidase 1 (or Cathepsin C) inhibitor verducatib in bronchiectasis (WBC 2026) - No abstract available

P2 data • Bronchiectasis • Pulmonary Disease • Respiratory Diseases • CTSC

Pediatric simulations of verducatib (BI 1291583) in adolescents to support Phase III dose selection (WBC 2026) - No abstract available

Clinical • P3 data • Pediatrics

Subgroup analysis: AIRLEAF® Phase II study of a dipeptidyl peptidase 1 (DPP1, or CatC) inhibitor, verducatib, in adults with non–cystic fibrosis bronchiectasis (WBC 2026) - No abstract available

Clinical • P2 data • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Pharmacotherapy options and drug development in bronchiectasis: spotlight on dipeptidyl-peptidase inhibitors. (PubMed, Expert Opin Pharmacother) - "The recent regulatory approval of brensocatib, a DPP-1 inhibitor, represents a milestone in the development of targeted therapies for bronchiectasis.This review provides a narrative overview of available treatments for bronchiectasis, with a particular focus on DPP-1 inhibitors, and discusses their potential role and integration into clinical practice...A major challenge will be identifying the patients most likely to benefit. Despite uncertainties, these agents have the potential to redefine treatment for this complex disease."

Journal • Review • Bronchiectasis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study to Test How Verducatib is Taken up in the Body of Healthy Chinese Participants (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P1 trial

Final Pooled Data From Phase II Studies (AIRLEAF®, CLAIRLEAF®) of the Dipeptidyl Peptidase 1 (Or Cathepsin C) Inhibitor Verducatib in Bronchiectasis (ATS 2026) - No abstract available

P2 data • Bronchiectasis • Pulmonary Disease • Respiratory Diseases • CTSC

Bronchiectasis Treatment Goals, Unmet Needs, and Emerging Therapies: A Podcast. (PubMed, Pulm Ther) - "In the phase 3, 52-week ASPEN trial, brensocatib significantly reduced exacerbation burden, and the 25-mg dose reduced lung function decline and nominally significantly improved patient-reported symptoms compared with placebo. Additional therapies in development include other DPP1 inhibitors (verducatib and HSK31858) and drugs targeting phosphodiesterase 3/4 inhibition (ensifentrine) and anti-interleukin-33 (itepekimab). Overall, the future is promising for patients with the historically neglected and underdiagnosed disease bronchiectasis, with growing awareness and new therapeutic tools becoming available. Podcast (MP4 81554 KB)."

Journal • Bronchiectasis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pediatrics • Pulmonary Disease • Respiratory Diseases • IL33

A Phase II study (CLAIRAFLY®) evaluating safety, tolerability, pharmacokinetics and pharmacodynamics of the DPP1 (CatC) inhibitor BI 1291583 in cystic fibrosis: Effects of CFTR modulator therapy use (NACFC 2025) - P2 | " Of the 22 participants randomized, 50.0% had stable CFTRmt use at baseline (9 participants (40.9%) on elexacaftor/ivacaftor/tezacaftor). This study suggests that CFTRmt use has no effect on the BI 1291583 safety profile or PK. Sputum NE activity was reduced for people with CFBE with or without CFTRmt, with a potential for greater effect relative to baseline in people on CFTRmt. Interestingly, in this population with a history of PExs, baseline sputum NE activity was similar regardless of CFTRmt use, with both groups having similar levels to those seen in AIRLEAF®."

Clinical • P2 data • PK/PD data • Bronchiectasis • Cystic Fibrosis • Dental Disorders • Genetic Disorders • Immunology • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Periodontitis • Pulmonary Disease • Respiratory Diseases • CFTR • CTSC • ELANE

A Phase II study (CLAIRAFLY®) to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of the dipeptidyl peptidase 1 (cathepsin C) inhibitor BI 1291583 in adults with cystic fibrosis bronchiectasis (WBC 2025) - P2 | "The safety, tolerability, PK and PD of BI 1291583 were similar in both CLAIRAFLY® and AIRLEAF®. These findings support the inclusion of both people with CFBE and non–CFBE in the Phase III AIRTIVITY® study."

Clinical • P2 data • PK/PD data • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CTSC • ELANE

Study design of a Phase III study (AIRTIVITY®) of the novel dipeptidyl peptidase 1 (cathepsin C) inhibitor BI 1291583 in people with bronchiectasis (WBC 2025) - "AIRTIVITY® intends to further evaluate evidence for the efficacy, safety and tolerability of BI 1291583 2.5mg in a large and broad population of people with bronchiectasis. AIRTIVITY® is due to begin in Q2 2025."

P3 data • Asthma • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • CTSC

Results from a Phase II study (AIRLEAF®) of the dipeptidyl peptidase 1 (cathepsin C) inhibitor BI 1291583 in adults with bronchiectasis (WBC 2025) - "Results from AIRLEAF® show that the DPP1 inhibitor BI 1291583 at a dose of 2.5mg and 5mg reduced the risk of experiencing a PEx in adults with bronchiectasis, while demonstrating a similar safety profile to placebo. These results support the continued clinical development of BI 1291583, with the 2.5mg dose to be assessed in the Phase III AIRTIVITY® study that is planned to begin in Q2 2025."

Clinical • P2 data • Bronchiectasis • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • CTSC