FDA Issues CRL for Avasopasem for Severe Mucositis in Head & Neck Cancer

The FDA gave priority review to the NDA for avasopasem for patients with radiotherapy-induced severe oral mucositis in February 2023.

The FDA has issued a complete response letter to a new drug application (NDA) for avasopasem manganese (GC4419) as a treatment for radiotherapy-induced severe oral mucositis among patients with head and neck cancer receiving standard-of-care, according to a press release from Galera Therapeutics, Inc.¹

The regulatory agency highlighted that data in the NDA, which included supporting findings from the phase 3 ROMAN trial (NCT03689712) and the phase 2b GT-201 trial (NCT02508389), were not sufficient for demonstrating the efficacy and safety of avasopasem in reducing severe oral mucositis in this patient population. Additionally, investigators were required to include findings from an additional clinical trial as part of resubmitting their NDA.

Developers are looking to request a Type A meeting with the FDA to discuss the next steps for resubmitting the NDA for avasopasem.

“This response from the FDA is deeply disappointing for Galera and for patients [with] severe oral mucositis,” Mel Sorensen, MD, president and chief executive officer at Galera, said in the press release. “We continue to believe in avasopasem’s potential to bring a meaningful benefit to these patients who currently have no FDA-approved drugs for this debilitating condition.”

According to findings from the ROMAN trial that investigators presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, treatment with avasopasem resulted in a severe oral mucositis rate of 54% compared with 64% in patients who received placebo over the course of intensity-modulated radiation therapy (IMRT; relative risk [RR], 0.84; P = .045).² Avasopasem also produced a 56% reduction in the median duration of severe oral mucositis relative to placebo (18 days vs 8 days; P = .002) as well as a 27% reduction in grade 4 incidence of oral mucositis (33% vs 24%; P = .052) and a 24% reduction in the mean number of days of grade 4 oral mucositis (7.2 days vs 5.5 days; P = .143).

In the phase 3 ROMAN trial, 407 patients with locally advanced head and neck cancer were randomly assigned 3:2 to receive 90 mg oof avasopasem via a 60-minute infusion or matched placebo. The primary end point of the trial was the cumulative incidence of severe oral mucositis, and secondary end points included duration of severe oral mucositis and incidence and duration of grade 4 events.

In the GT-201 trial, a 90 mg dose of avasopasem meaningfully reduced severe oral mucositis duration (P = .024)³. The agent also reduced the rate of severe oral mucositis related to IMRT (P = .009), including grade 4 oral mucositis (P = .045), relative to placebo.

In the phase 2b GT-210 trial, 223 patients with locally advanced head and neck cancer were randomly assigned 1:1:1 to receive 30 mg or 90 mg of avasopasem, or placebo as an infusion plus standard-of-care radiotherapy cisplatin. The primary end point of the trial was duration of severe oral mucositis per World Health Organization criteria. Secondary end points included treatment-emergent adverse effects (AEs) and the rate of severe oral mucositis.

Across both trials, AEs following treatment with avasopasem were comparable with those caused by radiotherapy and cisplatin outside of some increases in rates of hypotension and mild nausea.4 Additionally, there were some nominal decreases in AEs including oropharyngeal pain, radiation skin injury, tinnitus, and acute kidney injury.

The FDA gave priority review to the NDA for avasopasem for patients with radiotherapy-induced severe oral mucositis in February 2023.⁴

References

1. Galera receives complete response letter from U.S. FDA for avasopasem manganese. News release. Galera Therapeutics, Inc. August 9, 2023. Accessed August 10, 2023. bit.ly/45oPvLY
2. 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
3. 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. doi:10.1200/JCO.19.01507
4. Galera announces FDA acceptance and priority review of avasopasem NDA for radiotherapy-induced severe oral mucositis. News release. Galera Therapeutics. February 15, 2023. Accessed August 10, 2023. bit.ly/3EbuLfj