RG6173 / Roche - LARVOL DELTA

Airway tryptase levels inform the lack of clinical efficacy of the tryptase inhibitor MTPS9579A in asthma. (PubMed, Allergy) - "The MTPS9579A dose tested in the phase 2a study was insufficient to inhibit tryptase in bronchial lining fluid, likely contributing to the observed lack of efficacy."

Journal • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A mechanistic PK/PD model to enable dose selection of the potent anti-tryptase antibody (MTPS9579A) in patients with moderate-to-severe asthma. (PubMed, Clin Transl Sci) - "The PK/PD model predicted that 1800 mg MTPS9579A i.v. q4w results in 95.7% suppression of active tryptase at the steady-state trough concentration. Understanding how the exposure-response relationship of MTPS9579A in healthy subjects translates to patients with asthma is critical for future clinical studies assessing tryptase inhibition in the airway of patients with moderate-to-severe asthma."

Journal • PK/PD data • Allergy • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Late Breaking Abstract - Effects of anti-tryptase antibody in upper and lower airway of asthmatics (ERS 2022) - "In nasosorption, complete inhibition of active tryptase was observed post-dose at both dose levels; however, no consistent reduction was observed in bronchosorption at the highest dose tested. PK/PD modeling supports that lack of PD effect in bronchosorption is likely due to insufficient MTPS9579A partitioning to inhibit the high levels of active tryptase in the lower airway."

Late-breaking abstract • Asthma • Immunology • Respiratory Diseases

A Study of MTPS9579A in Participants With Refractory Chronic Spontaneous Urticaria (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Genentech, Inc. | N=240 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MTPS9579A in Patients With Asthma Requiring Inhaled Corticosteroids and a Second Controller (clinicaltrials.gov) - P2a | N=135 | Completed | Sponsor: Genentech, Inc. | Active, not recruiting ➔ Completed

Trial completion • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A Study of MTPS9579A in Participants With Refractory Chronic Spontaneous Urticaria (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Genentech, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Spontaneous Urticaria • Dermatology • Urticaria

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MTPS9579A in Patients With Asthma Requiring Inhaled Corticosteroids and a Second Controller (clinicaltrials.gov) - P2a; N=134; Active, not recruiting; Sponsor: Genentech, Inc.; Trial completion date: Sep 2022 ➔ May 2022

Clinical • Trial completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A Study of MTPS9579A in Participants With Refractory Chronic Spontaneous Urticaria (clinicaltrials.gov) - P2; N=240; Not yet recruiting; Sponsor: Genentech, Inc.

Clinical • New P2 trial • Chronic Spontaneous Urticaria • Dermatology • Urticaria

Dose-dependent inactivation of airway tryptase with a novel dissociating anti-tryptase antibody (MTPS9579A) in healthy participants: a randomized trial. (PubMed, Clin Transl Sci) - "A favorable safety and tolerability profile supports further assessment of MTPS9579A in asthma. Understanding the exposure-response relationships using the novel PD biomarker will help inform clinical development, such as dose selection or defining patient subgroups."

Clinical • Journal • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MTPS9579A in Patients With Asthma Requiring Inhaled Corticosteroids and a Second Controller (clinicaltrials.gov) - P2a; N=160; Recruiting; Sponsor: Genentech, Inc.; Trial completion date: Dec 2021 ➔ Sep 2022; Trial primary completion date: Dec 2021 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date • Asthma • Immunology • Respiratory Diseases

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MTPS9579A in Patients With Asthma Requiring Inhaled Corticosteroids and a Second Controller (clinicaltrials.gov) - P2a; N=160; Recruiting; Sponsor: Genentech, Inc.; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open • Asthma • Respiratory Diseases

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MTPS9579A in Patients With Asthma Requiring Inhaled Corticosteroids and a Second Controller (clinicaltrials.gov) - P2a; N=160; Active, not recruiting; Sponsor: Genentech, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Asthma • Immunology • Respiratory Diseases

Local Airway Concentration of Anti-Tryptase Antibody (MTPS9579A) Predicts Extent of Tryptase Disruption (AAAAI 2020) - "Local airway pharmacokinetics can be used to predict tryptase activity levels in the upper airway and may be extrapolated to the lung using PK/PD modeling. Future studies will explore how this work translates to asthmatics and to further explore the relationship between the PKPD in upper and lower airway."

Tryptase

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MTPS9579A in Patients With Asthma Requiring Inhaled Corticosteroids and a Second Controller (clinicaltrials.gov) - P2a; N=160; Recruiting; Sponsor: Genentech, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Late Breaking Abstract - Dose-dependent inactivation of airway tryptase with a novel dissociating anti-Tryptase antibody (MTPS9579A) in healthy volunteers (ERS 2019) - "A novel immunoassay was used to demonstrate for the first time that an investigative antibody therapeutic (MTPS9579A) can inhibit tryptase activity in the upper airway. A favorable safety and tolerability profile supports further assessment of MTPS9579A in asthma. PKPD relationship may help inform future trials."

Clinical • Late-breaking abstract

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MTPS9579A in Patients With Asthma Requiring Inhaled Corticosteroids and a Second Controller (clinicaltrials.gov) - P2a; N=160; Not yet recruiting; Sponsor: Genentech, Inc.

Clinical • New P2a trial