The Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for avasopasem manganese (GC4419) for radiotherapy (RT)-induced severe oral mucositis (SOM) in patients with head and neck cancer undergoing standard of care treatment.
Avasopasem is a selective dismutase mimetic designed to convert superoxide to hydrogen peroxide, thereby stopping the cascade that results in radiation damage to normal tissue. The NDA is supported by the randomized, double-blind, placebo-controlled phase 3 ROMAN trial (ClinicalTrials.gov Identifier: NCT03689712) and the phase 2b GT-201 (ClinicalTrials.gov Identifier: NCT02508389) trial. These studies enrolled a total of 678 patients with locally advanced, nonmetastatic squamous cell carcinoma of the head and neck.
In the ROMAN trial (N=455), results showed that treatment with avasopasem met the primary endpoint demonstrating a statistically significant 16% relative reduction in the incidence of SOM (54% vs 64%; P =.045) and a 56% relative reduction in the duration of SOM (median, 8 vs 18 days; P =.002) compared with placebo. There were also improvements observed across multiple secondary and exploratory endpoints, including the incidence and duration of grade 4 incidence of SOM.
An analysis at 1 year showed that avasopasem did not affect the treatment benefit of standard of care chemoradiotherapy. Tumor outcomes and overall survival were observed to be similar in the avasopasem and placebo arms.
In the GT-201 trial, treatment with avasopasem statistically significantly reduced the duration of SOM compared with placebo (median, 1.5 days vs 19 days; P =.024). Avasopasem was also associated with a lower incidence of SOM (43% vs 65%; P =.009) and grade 4 SOM (16% vs 30%; P =.045) compared with placebo.
“The impact of SOM, the most burdensome toxicity of standard-of-care RT, on a patient’s physical and psychological wellbeing is substantial, particularly when hospitalization and surgical placement of feeding tubes to maintain nutrition and hydration are required,” said Mel Sorensen, MD, President and Chief Executive Officer of Galera Therapeutics. “In some patients, SOM is so debilitating that they may delay and/or discontinue potentially curative RT, undermining their care. Avasopasem, if approved, has the potential to reduce pain and suffering for these patients, as well as reduce the costs associated with hospitalizations, surgical placement of feeding tubes, and other treatment burdens.”
A Prescription Drug User Fee Act target date of August 9, 2023 has been set for the application.
- Galera announces FDA acceptance and Priority Review of avasopasem NDA for radiotherapy-induced severe oral mucositis. News release. Galera Therapeutics, Inc. Accessed February 15, 2023. https://www.globenewswire.com/news-release/2023/02/15/2608650/0/en/Galera-Announces-FDA-Acceptance-and-Priority-Review-of-Avasopasem-NDA-for-Radiotherapy-Induced-Severe-Oral-Mucositis.html.
- Anderson CM, 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. Published online October 16, 2019. doi:10.1200/JCO.19.01507
- 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. Published online June 2, 2022. doi:10.1200/JCO.2022.40.16_suppl.6005