GC4419 Receives FDA Breakthrough Therapy Designation for the Reduction of Severe Oral Mucositis


On February 28, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to GC4419, a highly selective and potent small molecule dismutase mimetic, for the reduction of the duration, incidence, and severity of severe oral mucositis induced by radiation therapy with or without systemic therapy.

Approximately 70% of patients with head and neck cancer receiving radiotherapy develop severe oral mucositis, a painful complication caused by excessive superoxide generated during treatment that breaks down epithelial cells in the mouth. By leveraging a dismutase mimetic platform to rapidly convert the superoxide generated by radiation therapy into hydrogen peroxide, GC4419 is thought to reduce the duration, incidence, and severity of radiation-induced severe oral mucositis.

There is currently no drug approved to prevent or treat severe oral mucositis in patients with head and neck cancer.

“Breakthrough Therapy designation from the FDA further validates the meaningful efficacy and safety results GC4419 demonstrated in our recent phase IIb clinical trial and highlights the urgent need for a treatment option for severe oral mucositis,” said Mel Sorensen, MD, President and CEO of Galera Therapeutics. “We look forward to working closely with the FDA on the continued development of GC4419 for the reduction of severe oral mucositis in patients in order to efficiently advance the clinical program and ultimately bring GC4419 to patients in need.”

Clinical Trial

Breakthrough Therapy designation for GC4419 was granted based on the data from Galera’s double-blind, randomized, placebo-controlled phase IIb clinical trial in 223 patients with head and neck cancer.

In the trial, GC4419 reduced the duration of severe oral mucositis from 19 days to 1.5 days (92%), the incidence of severe oral mucositis through completion of radiation by 34%, and the severity of patients’ oral mucositis by 47%, while demonstrating acceptable safety when added to a standard radiotherapy regimen.

GC4419 has also received Fast Track designation from the FDA for the reduction of the severity and incidence of radiation and chemotherapy-induced oral mucositis.

About GC4419

GC4419 is a highly selective and potent small molecule dismutase mimetic that closely mimics the activity of human superoxide dismutase enzymes. GC4419 works to reduce elevated levels of superoxide caused by radiation therapy by rapidly converting superoxide to hydrogen peroxide and oxygen. Left untreated, elevated superoxide can damage noncancerous tissues and lead to debilitating side effects, including oral mucositis, which can limit the antitumor efficacy of radiation therapy.

Conversion of elevated superoxide to hydrogen peroxide, which is selectively more toxic to cancer cells, can also enhance the effect of radiation on tumors, particularly with stereotactic body radiation therapy, which produces high levels of superoxide. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.