ABBV-3373 / AbbVie - LARVOL DELTA

An anti-TNF-glucocorticoid receptor modulator antibody-drug conjugate is efficacious against immune-mediated inflammatory diseases. (PubMed, Sci Transl Med) - "Clinical data for a human anti-TNF-GRM ADC (ABBV-3373) from a single ascending dose phase 1 study in healthy volunteers demonstrated antibody-like pharmacokinetic profiles and a lack of impact on serum cortisol concentrations at predicted therapeutic doses. These data suggest that an anti-TNF-GRM ADC may provide improved efficacy beyond anti-TNF alone in immune mediated diseases while minimizing systemic side effects associated with standard GC treatment."

Journal • Contact Dermatitis • Immunology • Inflammation • Oncology • Rheumatoid Arthritis • Rheumatology

Minimising the payload solvent exposed hydrophobic surface area optimises the antibody-drug conjugate properties. (PubMed, RSC Med Chem) - "Solving the crystal structure of compound 2, the GRM payload from ABBV-3373 and ABBV-154, in the ligand binding domain of the glucocorticoid receptor (GR) revealed key information to facilitate optimal ADC payload design. Confirmation of the stereochemistry of the acetal in compound 2 as (R) was established. Finally, the importance of minimising the exposed hydrophobic surface area of a payload to reduce the negative impact on the properties of resulting ADCs, like aggregation, was rationalised by comparison of (R)-acetal compound 2 and (S)-acetal compound 3."

Journal • Oncology

A first-in-human study of the novel immunology antibody drug conjugate, ABBV-3373, in healthy participants. (PubMed, Br J Clin Pharmacol) - "ABBV-3373 had favorable PK profiles, manageable immunogenicity, and was generally well tolerated. Except for a transient effect at 900 mg IV, there was no apparent impact on serum cortisol. Study results supported further clinical development of ABBV-3373."

Journal • P1 data • Inflammation

Discovery of ABBV-3373, an Anti-TNF Glucocorticoid Receptor Modulator Immunology Antibody Drug Conjugate. (PubMed, J Med Chem) - "In a chronic mouse arthritis model, mouse anti-TNF GRM ADCs were efficacious after a single dose of 10 mg/kg i.p. for over 30 days. Data on the unconjugated payloads and mouse surrogate anti-TNF ADCs identified payload 17 which was conjugated to a human anti-TNF antibody and advanced to the clinic as ABBV-3373."

Journal • Contact Dermatitis • Immunology • Oncology • Rheumatology

[VIRTUAL] ANTI-TNF GLUCOCORTICOID RECEPTOR MODULATOR ANTIBODY DRUG CONJUGATE FOR THE TREATMENT OF AUTOIMMUNE DISEASES (EULAR 2021) - "These data suggest that an anti-TNF ADC delivering a GRM payload into activated immune cells may provide improved efficacy in immune mediated diseases, while minimizing systemic side effects associated with standard GC treatment."

Contact Dermatitis • Immunology • Inflammation • Rheumatoid Arthritis • Rheumatology

[VIRTUAL] EFFICACY AND SAFETY OF ABBV-3373, A NOVEL ANTI-TNF GLUCOCORTICOID RECEPTOR MODULATOR ANTIBODY DRUG CONJUGATE, IN PATIENTS WITH MODERATE TO SEVERE RHEUMATOID ARTHRITIS DESPITE METHOTREXATE THERAPY: A PHASE 2A PROOF OF CONCEPT STUDY (EULAR 2021) - "Background: ABBV-3373 is a novel antibody drug conjugate composed of adalimumab (ADA) linked to a proprietary and highly potent glucocorticoid receptor modulator (the anti-inflammatory payload) currently evaluated for the treatment of rheumatoid arthritis (RA). These data demonstrate the clinical efficacy of ABBV-3373 and its potential to provide improved outcomes for RA pts compared to ADA. The safety profile of ABBV-3373 was generally similar to ADA."

Clinical • P2a data • Immunology • Infectious Disease • Inflammatory Arthritis • Pneumonia • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P2; N=48; Active, not recruiting; Sponsor: AbbVie; Recruiting ➔ Active, not recruiting; Trial completion date: Jun 2021 ➔ Dec 2023

Clinical • Enrollment closed • Trial completion date • Immunology • Rheumatoid Arthritis • Rheumatology • CRP

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P1; N=45; Recruiting; Sponsor: AbbVie; Trial primary completion date: Dec 2020 ➔ Jun 2021

Clinical • Trial primary completion date • Immunology • Rheumatoid Arthritis • Rheumatology • CRP

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P1; N=45; Recruiting; Sponsor: AbbVie; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Immunology • Rheumatoid Arthritis • Rheumatology • CRP

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P2; N=45; Recruiting; Sponsor: AbbVie; Phase classification: P1 ➔ P2; Trial completion date: Aug 2020 ➔ Jun 2021; Trial primary completion date: Aug 2020 ➔ Dec 2020

Clinical • Phase classification • Trial completion date • Trial primary completion date • Immunology • Rheumatoid Arthritis • Rheumatology • CRP

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P1; N=45; Not yet recruiting; Sponsor: AbbVie

Clinical • New P1 trial • Immunology • Rheumatoid Arthritis • Rheumatology • CRP

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P1; N=45; Recruiting; Sponsor: AbbVie; Trial completion date: Jun 2021 ➔ Aug 2020; Trial primary completion date: Jun 2021 ➔ Aug 2020

Clinical • Trial completion date • Trial primary completion date • Immunology • Rheumatoid Arthritis • Rheumatology • CRP

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P2; N=48; Completed; Sponsor: AbbVie; Recruiting ➔ Completed; N=133 ➔ 48

Clinical • Enrollment change • Trial completion • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P2; N=133; Recruiting; Sponsor: AbbVie; Active, not recruiting ➔ Recruiting; N=48 ➔ 133; Trial completion date: Dec 2023 ➔ Nov 2020; Trial primary completion date: Dec 2020 ➔ Jun 2020

Clinical • Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Immunology • Rheumatoid Arthritis • Rheumatology • CRP

"ABBV-3373, anti-THF antibody conjugated for rheumatoid arthritis @AbbVie. First results in humans. #ASCPT2021" (@Cortellis)

Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology