FDA Grants Priority Review to NDA of Avasopasem for RT-Induced Severe Oral Mucositis

The FDA has accepted for filing and granted priority review to the new drug application (NDA) for avasopasem manganese (GC4419) for the treatment of radiotherapy-induced severe oral mucositis (SOM) in patients with head and neck cancer who are receiving standard-of-care treatment, according to Galera Therapeutics, Inc.¹

The basis of the NDA comes from data of the phase 2b GT-201 (NCT02508389) and phase 3 ROMAN (NCT03689712) trials, which evaluated avasopasem in a total of 678 patients.

In GT-201, avasopasem was given at 90 mg and led to a significant reduction in median SOM duration vs treatment with placebo (1.5 vs 19 days; P = .024).² Findings showed that 43% of patients given treatment with avasopasem experienced SOM compared with 65% of patients given placebo (P = .009). Moreover, grade 4 SOM was seen in 16% of patients given avasopasem and 30% of patients given placebo arm (P = .045).

Then, the phase 3 ROMAN study was the confirmatory trial that demonstrated avasopasem significantly reduced incidence of SOM in this patient population. Data from the study were presented during the 2022 ASCO Annual Meeting, which revealed that through the course of intensity-modulated radiation therapy (IMRT), the incidence rate of SOM was decreased for patients who received avasopasem (n = 241) at 54% vs 64% among those who received placebo (n = 126; relative risk, 0.84; P = .045). The study met its primary end point.

“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, said in a press release.1

Avasopasem is a selective small molecule dismutase mimetic. The agent is designed to protect normal cells from radiation through converting radiation-induced superoxide into hydrogen peroxide.

The FDA set a Prescription Drug User Fee Act (PDUFA) target date of August 9, 2023, and the regulatory agency stated in its acceptance of filing letter that they are not planning to hold an advisory committee meeting for the application.

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

The primary end point of the study was the number of days of SOM in the 90 mg cohort vs that in the placebo cohort.

After the 2-year follow-up, patients given avasopasem plus radiotherapy and cisplatin had similar tumor outcomes and overall survival rates compared with patients who received the placebo and the standard of care. Regarding safety, avasopasem was generally well tolerated compared with placebo.

These results showed that avasopasem protected patients with head and neck cancers from SOM and did not affect the treatment benefit of standard-of-care chemoradiotherapy.

Then, the randomized, double-blind, placebo-controlled ROMAN trial enrolled 455 patients with locally advanced head and neck cancer who were administered standard-of-care radiotherapy in addition to cisplatin for a total of 7 weeks. Patients were randomly assigned 3:2 to receive avasopasem or placebo via infusion on the days they received radiation.

The primary end point of the study was cumulative incidence of SOM from the first IMRT fraction until the end of the study treatment periods with key the secondary end points of duration of SOM (total number of days) and total number of days that grade 4 SOM endured. Additional end points included safety and tolerability, as well as tumor outcomes at 1 to 2 years of follow-up.

In the exploratory analysis of ROMAN, findings showed the clinical benefit that avasopasem had in reducing the burden of SOM. Avasopasem also showed a meaningful reduction in long-term loss of kidney function associated with concurrent cisplatin.

When avasopasem was given prior to IMRT, patients had a 56% reduction in median duration of SOM vs with placebo (8 vs 18 days, respectively; P = .002). Patients given avasopasem vs placebo 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).²

Additionally, safety data were consistent with previously reported data from avasopasem.

“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,” added Sorensen, in the press release.

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 20, 2023. https://investors.galeratx.com/news-releases/

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