Gimsilumab is an investigational, fully human IgG1 monoclonal antibody being investigated for its potential in the treatment of multiple inflammatory diseases and cancer. The drug specifically targets granulocyte-macrophage colony stimulating factor (GM-CSF), a molecule shown in preclinical studies to be involved in autoimmune diseases, including rheumatoid arthritis, multiple sclerosis and asthma.
Gimsilumab is currently being investigated as a monoclonal antibody for its potential in the treatment of rheumatoid arthritis (RA), a chronic, systemic, inflammatory disorder that attacks the synovial lining in joints and leads to inflammation, joint erosion and damage to surrounding tissue. A clinical trial application (CTA) and Investigational New Drug application (IND) for gimsilumab were approved by the regulatory authorities in the Netherlands and the United States. A Phase 1 study (NCT01357759), MORAb-022-001, in healthy volunteers and patients with rheumatoid arthritis was completed in July 2014.
MORAb-022-001 was a single-dose, dose-ascending, placebo-controlled, Phase 1 trial evaluating the safety and tolerability of the investigational, anti-GM-CSF, monoclonal antibody, gimsilumab, in healthy subjects (n=26) and mild-to-moderate Rheumatoid Arthritis (RA) patients (n=25).
In this study, all of the gimsilumab dose cohorts in the RA patients demonstrated decreases in their median 28-joint Disease Activity Score based on C-reactive protein (DAS28 (CRP)) by Day 5; however, only the highest single-dosed 10 mg/kg cohort showed a median decrease of more than 1.2 units, which is considered clinically meaningful according to the European League Against Rheumatism (EULAR). The overall incidence of Treatment Emergent Adverse Events was low, and there were no severe adverse events reported during the study for any subject. There were no Rheumatology Common Toxicity Criteria (RCTC) Grade 3 or 4 adverse events reported for subjects with RA in any dose cohort during the study. The pharmacokinetics for gimsilumab increased approximately in a linear, dose-proportional manner.
The responses observed with investigational monoclonal antibody, gimsilumab, in this Phase 1 trial with mild-to-moderate RA patients are very encouraging and support further research in randomized trials to evaluate the concept of inhibiting the cytokine GM-CSF in the treatment of patients with RA.
In addition, recent preclinical data generated by Morphotek have identified its role in oncology, whereby blocking GM-CSF with gimsilumab results in a pro-immunity microenvironment and associated tumor tissue death. Further preclinical studies are being conducted to position this compound for entry into clinical testing in oncology indications.
Current Clinical Studies
Gimsilumab Phase 1 Study (Completed)
This clinical study was a Phase 1, randomized, double-blind, placebo-controlled, single-dose, dose-escalation trial of gimsilumab in healthy patients and patients with rheumatoid arthritis.
This trial to evaluate the safety and tolerability of single escalating intravenous (IV) doses of gimsilumab in healthy patients and patients with rheumatoid arthritis (RA) has been completed. The top-line data were reported in a December 7, 2015 press release.
For more information visit ClinicalTrials.gov. (Identifier: NCT01357759)
The information contained herein is investigational and is not intended to make claims of safety or efficacy prior to approval by the FDA or other regulatory authorities. There is no guarantee that the agents described or their uses will be approved by the FDA or other regulatory authorities.