Author: Chris Ryan

The FDA has granted priority review to the new drug application (NDA) for avasopasem manganese (GC4419) as a treatment for radiotherapy-induced severe oral mucositis (SOM) in patients with head and neck cancer undergoing standard-of-care treatment.1

The NDA was supported by data from the phase 2b GT-201 (NCT02508389) and phase 3 ROMAN (NCT03689712) trials, which enrolled a total of 678 patients.

Findings from GT-201 demonstrated that 90 mg avasopasem induced a significant reduction in median SOM duration compared with placebo (1.5 vs 19 days; P = .024).2 Additionally, 43% of patients treated with avasopasem experienced SOM compared with 65% of patients who received placebo (P = .009). Grade 4 instances of SOM occurred in 16% and 30% of patients in the avasopasem and placebo arms, respectively (P = .045).

In the ROMAN confirmatory trial, avasopasem also significantly reduced incidence of SOM.3 Data presented during the 2022 ASCO Annual Meeting showed that through the course of intensity-modulated radiation therapy (IMRT), SOM was reported in 54% of patients administered avasopasem (n = 241) vs 64% of those given placebo (n = 166; relative risk [RR], 0.84; P = .045), meeting the trial’s primary end point.

Additionally, when avasopasem was given prior to IMRT, patients experienced a 56% reduction in median duration of SOM compared with placebo (8 vs 18 days, respectively; P = .002). Compared with placebo, these patients also had a 27% reduction in incidence of grade 4 SOM (33% vs 24%; P = .052) and a 24% reduction in the mean number of days of grade 4 incidence (7.2 vs 5.5 days; P = .143).

The FDA assigned a Prescription Drug User Fee Act (PDUFA) target date of August 9, 2023. The regulatory agency indicated in its acceptance of filing letter that it is not planning to hold an advisory committee meeting for the application.1

“We are very pleased by the FDA’s acceptance of our NDA with priority review, which is a significant milestone as we prepare to bring this important product, if approved, to patients as soon as possible, and we look forward to working closely with the FDA during the review process,” Mel Sorensen, MD, president and chief executive officer of Galera Therapeutics, stated in a news release.

Avasopasem is a selective small molecule dismutase mimetic designed to protect normal cells, but not cancer cells, from radiation by converting radiation-induced superoxide, which initiates the tissue damage and inflammatory cascade that results in oral mucositis, into hydrogen peroxide.

GT-201 was a randomized, double-blind, placebo-controlled trial that enrolled 223 patients with locally advanced head and neck cancer. Patients received 7 weeks of standard-of-care radiotherapy plus cisplatin, and they were randomly assigned in a 1:1:1 fashion to receive 30 mg of avasopasem, 90 mg of avasopasem, or placebo by infusion on the days they were administered radiation.

The primary end point was the number of days of SOM in the 90 mg cohort compared with the placebo cohort.

Two-year follow-up from the trial showed that patients treated with avasopasem plus radiotherapy and cisplatin achieved similar tumor outcomes and overall survival as patients who received placebo plus standard of care.

Regarding safety, avasopasem was not associated with a clinically meaningful increase in the adverse effect profile expected for the target patient population receiving standard-of-care radiotherapy.

ROMAN was also a randomized, double-blind, placebo-controlled trial that enrolled 455 patients with locally advanced head and neck cancer. All patients were given standard-of-care radiotherapy plus cisplatin for seven weeks and randomly assigned in a 3:2 fashion to receive avasopasem or placebo by infusion on the days they received radiation.

An exploratory analysis of ROMAN also demonstrated the clinical benefit of avasopasem in reducing the burden of SOM, as well as a meaningful reduction in long-term loss of kidney function associated with concurrent cisplatin. Safety data were consistent with previously reported data from avasopasem.

1. Galera announces FDA acceptance and priority review of avasopasem NDA for radiotherapy-induced severe oral mucositis. News release. Galera Therapeutics. February 15, 2023. Accessed February 15, 2023.
2. Anderson CCM, Lee CM, Saunders DP, et al. Phase IIb, randomized, double-blind trial of GC4419 versus placebo to reduce severe oral mucositis due to concurrent radiotherapy and cisplatin for head and neck cancer. J Clin Oncol. 2019;37(34):3256-3265. doi:10.1200/JCO.19.01507
3. Anderson CM, Lee CM, Kelley Jr, et al. ROMAN: phase 3 trial of avasopasem manganese (GC4419) for severe oral mucositis (SOM) in patients receiving chemoradiotherapy (CRT) for locally advanced, nonmetastatic head and neck cancer (LAHNC). J Clin Oncol. 2022;40 (suppl 16):abstr 6005. doi:10.1200/JCO.2022.40.16_suppl.6005