GC4419, also known as avasopasem manganese, has successfully completed two clinical trials to reduce severe oral mucositis in patients with head and neck cancer undergoing radiation therapy and also receiving cisplatin, a chemotherapy drug.1, 2 We demonstrated proof-of-concept with GC4419 for this indication in a randomized, double-blinded, placebo-controlled 223-patient Phase 2b trial. In the trial, GC4419 met the primary endpoint by demonstrating a 92% reduction in median duration of SOM in the 90 mg treatment arm as compared to placebo, which was statistically significant and consistent with the results of our Phase 1b/2a SOM trial.2 Key secondary endpoints evaluating the incidence and severity of SOM also demonstrated substantial dose-dependent reductions of 34% and 47%, respectively, in the 90 mg treatment arm, and GC4419 was well tolerated in this trial.2 The following chart depicts the course of SOM in each patient in the 90 mg treatment arm or the placebo arm who experienced at least one episode of SOM during the course of his or her treatment and follow-up. Each bar represents a single patient and illustrates the length of time between that patient’s first evaluated instance of SOM and his or her last evaluated instance of SOM, along with the severity of his or her SOM during that interval.
This chart demonstrates that (1) fewer patients in the 90 mg treatment arm developed SOM than in the placebo arm, (2) fewer patients in the 90 mg treatment arm developed Grade 4 OM than in the placebo arm, and (3) on average, SOM did not last as long for patients in the 90 mg treatment arm. This is consistent with the observed reductions in the individual numerical endpoints of median duration, incidence and severity.
In addition, as in our other clinical trials and pre-clinical studies to date, in this trial, the anti-cancer efficacy of radiotherapy was maintained through one year when combined with GC4419. Following consultation with the FDA, we initiated a single confirmatory, randomized, placebo-controlled Phase 3 registrational trial of a 90 mg dose of GC4419 in patients with locally advanced head and neck cancer receiving radiotherapy, which we refer to as the ROMAN Trial.
GC4419 has received Breakthrough Therapy and Fast Track designations from the U.S. Food and Drug Administration. For additional details on ongoing clinical trials with GC4419, please visit www.clinicaltrials.gov.