melrilimab (GSK3772847) / J&J, GSK - LARVOL DELTA

A model-based approach using GSK3772847, an anti-interleukin-33 receptor monoclonal antibody, as a showcase to predict SC administration PK and free target dynamics based on PK and total target measurements after IV administration. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Further, a secondary objective was to demonstrate that prediction of SC data is feasible, based on an existing IV model and typical values of mAb parameters reported for SC absorption. GSK3772847, a human immunoglobulin G2 sigma isotype (IgG2f) mAb that binds to the extracellular domain of the interleukin-33 receptor (IL-33R or ST2) and neutralizes IL-33-mediated ST2 signaling, was used as a model compound for mAbs in this study."

Journal • IL33

Safety, tolerability, and pharmacokinetics of a single ascending subcutaneous dose of GSK3772847 in healthy participants. (PubMed, Pharmacol Res Perspect) - "Target engagement was demonstrated by reduced free soluble interleukin 33 (sIL-33) concentrations and substantially increased total sIL-33 concentrations compared with baseline. Subcutaneously administered GSK3772847 was well tolerated in healthy participants, including cohorts of Japanese and Chinese participants, and shows consistent PK and PD across injection sites and ethnicities."

Journal • PK/PD data • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases • IL33

Efficacy and safety of GSK3772847 in participants with moderate-to-severe asthma with allergic fungal airway disease: A phase IIa randomized, multicenter, double-blind, sponsor-open, comparative trial. (PubMed, PLoS One) - P2 | "Lack of clinical benefits with GSK3772847 was likely due to the small sample size, highlighting the need for larger prospective studies."

Journal • P2a data • Asthma • Immunology • Infectious Disease • Oncology • Pulmonary Disease • Respiratory Diseases • IL33

A Study to Evaluate the Safety and Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of GSK3772847 in Healthy Participants (clinicaltrials.gov) - P1; N=64; Completed; Sponsor: GlaxoSmithKline; Recruiting ➔ Completed

Clinical • Trial completion • Asthma • Immunology • Respiratory Diseases

GSK culls top respiratory disease prospect, delivering another blow to IL-33 field (Fierce Pharma) - "GlaxoSmithKline has culled...a phase 2 asthma drug it once identified as a top prospect for its faltering respiratory business. The decision to dump IL33r antagonist GSK3772847 follows lackluster clinical data on rival candidates against the same target....The cessation of the phase 2 and setbacks to other anti-IL-33 drugs pointed to the possibility of GSK killing off GSK3772847. Even so, the dumping of the candidate, which GSK attributed to 'portfolio prioritization,' marks a swift decline for an asset..."

Discontinued • Asthma • Immunology

A Study to Evaluate the Safety and Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of GSK3772847 in Healthy Participants (clinicaltrials.gov) - P1; N=64; Recruiting; Sponsor: GlaxoSmithKline; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Asthma • Respiratory Diseases

Repeat Dose Study of GSK3772847 in Participants With Moderate to Severe Asthma With Allergic Fungal Airway Disease (AFAD) (clinicaltrials.gov) - P2; N=18; Terminated; Sponsor: GlaxoSmithKline; Active, not recruiting ➔ Terminated; Recruitment was terminated early before meeting target enrolment due to a high screen failure rate and the feasibility of completing the study in a timely way

Clinical • Trial termination • Asthma • Immunology • Respiratory Diseases

The First-in-Human Study of CNTO 7160, an Anti-Interleukin-33 Receptor Monoclonal Antibody, in Healthy Subjects and Patients with Asthma or Atopic Dermatitis. (PubMed, Br J Clin Pharmacol) - "This first-in-human study provides PK, PD, and safety data, supporting further clinical investigation of CNTO 7160 in patients with asthma and AD."

Clinical • Journal • P1 data • Asthma • Atopic Dermatitis • Dermatitis • Dermatology • Dermatopathology • Immunology • Respiratory Diseases

A Study to Evaluate the Safety and Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of GSK3772847 in Healthy Participants (clinicaltrials.gov) - P1; N=64; Not yet recruiting; Sponsor: GlaxoSmithKline

Clinical • New P1 trial • Asthma • Immunology • Respiratory Diseases

Repeat Dose Study of GSK3772847 in Participants With Moderate to Severe Asthma With Allergic Fungal Airway Disease (AFAD) (clinicaltrials.gov) - P2; N=18; Active, not recruiting; Sponsor: GlaxoSmithKline; N=46 ➔ 18

Clinical • Enrollment change

Repeat Dose Study of GSK3772847 in Participants With Moderate to Severe Asthma With Allergic Fungal Airway Disease (AFAD) (clinicaltrials.gov) - P2; N=46; Active, not recruiting; Sponsor: GlaxoSmithKline; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Interleukin-33 modulates inflammation and may be treated as a biomarker in endometriosis (ESHRE 2019) - "Wider implications of the findings: Whether IL-33 is involved in endometriosis alone or in combination with other factors is unclear; however, this molecule is possibly a potential biomarker and novel therapy target for managing endometriosis. Furthermore, the inhibitor of IL-33 (CNTO-7160), currently examined in clinical trials, may possibly be developed as new therapy for endometriosis."

Biomarker

Efficacy and Safety Study of GSK3772847 in Subjects With Moderately Severe Asthma (clinicaltrials.gov) - P2; N=168; Completed; Sponsor: GlaxoSmithKline; Active, not recruiting ➔ Completed

Clinical • Trial completion

Repeat Dose Study of GSK3772847 in Participants With Moderate to Severe Asthma With Allergic Fungal Airway Disease (AFAD) (clinicaltrials.gov) - P2; N=46; Recruiting; Sponsor: GlaxoSmithKline; Trial completion date: Oct 2019 ➔ Jan 2020; Trial primary completion date: Jul 2019 ➔ Oct 2019

Clinical • Trial completion date • Trial primary completion date

Efficacy and Safety Study of GSK3772847 in Subjects With Moderately Severe Asthma (clinicaltrials.gov) - P2; N=167; Active, not recruiting; Sponsor: GlaxoSmithKline; Phase classification: P1/2 ➔ P2

Clinical • Phase classification

GSK3772847: Proof-of-concept data from P1/2 trial (NCT03207243) for moderately severe asthma in H1 2019 (GSK) - Q4 2018 Results

P2 data