Anti–Oral Mucositis Drug Granted Breakthrough Status

The FDA has granted Breakthrough Therapy and Fast Track designation to GC4419, for reduction of severe oral mucositis caused by radiation therapy.

The US Food and Drug Administration (FDA) recently granted Breakthrough Therapy designation to GC4419 (Galera Therapeutics) for reduction of the duration, incidence, and severity of severe oral mucositis induced by radiation therapy with or without systemic therapy. The FDA has also granted GC4419 Fast Track designation, according to a news release from Galera Therapeutics.

GC4419 is a highly selective, potent small molecular dismutase mimetic. The drug is able to rapidly convert the superoxide generated by radiation therapy into hydrogen peroxide, thus reducing the effects of radiation-induced severe oral mucositis. (Superoxide damages epithelial cells in the mouth.)

The lead indication for GC4419 is in patients with head and neck cancer, for whom radiation therapy is a mainstay of treatment. Approximately 70% of patients receiving chemoradiotherapy for head and neck cancer develop severe oral mucositis, defined by the World Health Organization as grade 3 or 4. These patients typically experience significant pain and are unable to eat solid food or drink liquids.

GC4419 received the Breakthrough Therapy designation based on the results of a phase IIb clinical trial. In this double-blind study, 223 patients with head and neck cancer were randomly assigned in a 1:1:1 ratio to 30 mg of GC4419, 90 mg of GC4419, or placebo by infusion on the days that they received their radiation treatment.

The duration of oral mucositis was reduced by 92%-from 19 days to 1.5 days-in patients treated with GC4419 (P = .024). The drug also reduced the incidence of oral mucositis through completion of radiation by 34% (P = .009) and lessened the severity of the condition by 47% (P = .045).

In a separate news release, Galera Therapeutics announced dosing of the first patient in a phase I/II study of GC4419 in patients with pancreatic cancer. Preclinical data have shown that GC4419 has the potential to improve the effectiveness of radiation in harming cancer cells while preventing its toxicity in normal tissue.

“Our recently completed 223-patient Phase 2b trial of GC4419 in head and neck cancer demonstrated GC4419’s ability to limit radiation-induced healthy tissue damage by reducing the duration, incidence and severity of radiation and chemotherapy-induced oral mucositis,” Mel Sorensen, MD, President and CEO of Galera, said in the press release. “We seek to build upon these results with this anti-tumor trial in LAPC and generate robust data to demonstrate GC4419’s potential to change the management of radiation therapy by both protecting normal tissue and improving the effectiveness of radiation, making more surgical resections possible.”