FDA Grants Priority Review to Avasopasem for Treatment-Related Oral Mucositis

The FDA has accepted and granted priority review to a new drug application for avasopasem manganese (GC4419) for radiotherapy-induced severe oral mucositis in patients with head and neck cancer, according to a press release from Galera Therapeutics.¹

With a Prescription Drug User Fee Act date of August 9, 2023, avasopasem may become the first FDA-approved drug for reducing radiotherapy-induced severe oral mucositis in patients with head and neck cancer.

Currently, there are not any drugs approved by the FDA to reduce severe oral mucositis within this population. The Prescription Drug User Fee Act date has been set for August 9, 2023.

Data from the phase 3 ROMAN trial (NCT03689712) and the phase 2b GT-201 trial (NCT02508389) supported the new drug application for avasopasem, which collectively included a total of 678 patients. Findings from both trials identified clinically meaningful reductions in severe oral mucositis burdens, including a reduced incidence and number of days of severe oral mucositis, incidence of grade 4 oral mucositis, the inability to eat or drink, and delaying time to severe oral mucositis onset.

In the ROMAN trial, avasopasem also reduced cisplatin-induced chronic kidney disease by half after 1 year.

In both trials, patients who received avasopasem plus cisplatin and radiotherapy had similar tumor responses and overall survival as patients in the placebo arms, demonstrating that avasopasem protected patients from severe oral mucositis without affecting the benefit of chemotherapy.

“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,” Mel Sorensen, MD, president and chief executive officer of Galera Therapeutics, said in the press release.

Investigators of the randomized, double-blind, placebo-controlled phase 3 ROMAN trial assessed the capability of avasopasem in reducing radiation-induced severe oral mucositis in 455 patients with locally advanced head and neck cancer. Patients were randomized 3:2 to receive either 90 mg of avasopasem or placebo plus standard-of-care radiotherapy and cisplatin.

The primary end point of the ROMAN trial was incidence of severe oral mucositis, and a secondary end point was duration of severe oral mucositis. Exploratory end points included the time to severe oral mucositis onset and severe oral mucositis incidence at various times during delivery of cumulative radiotherapy.

Investigators of the randomized, double-blind, placebo-controlled phase 2b GT-201 trial assessed avasopasem in 223 patients with locally advanced head and neck cancer. Patients were randomly assigned 1:1:1 to either receive 30 mg or 90 mg of avasopasem or placebo via infusion plus standard-of-care radiotherapy and cisplatin.

One of the primary end points of the GT-201 trial was duration of severe oral mucositis among patients.

In the ROMAN and GT-201 trials, the reported adverse effects (AEs) were consistent with those typically associated with radiotherapy and cisplatin excluding some increases in hypotension and mild nausea with avasopasem. Investigators also highlighted nominal decreases in the rates of some AEs in both trials, including oropharyngeal pain, radiation skin injury, tinnitus, and acute kidney injury.

The FDA previously received the new drug application for avasopasem for the management of radiotherapy-induced severe oral mucositis in head and neck cancer in December 2022.²

References

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. bit.ly/3EbuLfj
2. Galera submits new drug application for avasopasem for severe oral mucositis. News release. Galera Therapeutics. December 12, 2022. Accessed February 15, 2023. https://bit.ly/3uJlztq