FDA Delivers Complete Response Letter to Avasopasem NDA for Severe Oral Mucositis

The new drug application (NDA) seeking the approval of avasopasem manganese (GC4419) as a treatment for radiotherapy-induced severe oral mucositis (SOM) in patients with head and neck cancer has received a complete response letter from the FDA.¹

According to an announcement from Galera Therapeutics, the FDA has stated that the data from the phase 3 ROMAN (NCT03689712) and phase 2b GT-201 (NCT02508389) trials failed to substantially demonstrate the agent’s safety and efficacy in reducing SOM for patients receiving radiotherapy. For the manufacturers to resubmit the NDA, they will need to produce data from an additional clinical trial.

“This response from the FDA is deeply disappointing for Galera and for patients who suffer from SOM,” Mel Sorensen, MD, president and chief executive officer of Galera Therapeutics, stated in a news 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.

Avasopasem is a selective dismutase mimetic that was designed to treat SOM in patients with locally advanced head and neck cancer and to reduce radiotherapy-induced esophagitis in patients with lung cancer.

The initial NDA was supported by findings from the phase 3 ROMAN trial (NCT03689712). The trial enrolled patients with locally advanced head and neck cancer to receive 60-72 Gy of intensity-modulated radiation therapy plus cisplatin. For those who were randomly assigned to receive 90 mg of avasopasem 1 hour prior to their radiotherapy fraction (n = 241), the incidence of severe oral mucositis was 54%. For those who received placebo (n = 166), the rate of SOM was 33%, and this 27% difference in occurrence rate was deemed significantly significant (P = .052). The median duration of SOM throughout was 8 days vs 18 days, respectively, which was also statistically significant (P = 0.002).²

Patients who received the treatment also experienced a median onset SOM time of 49 days, while those in the placebo arm had 38 median days to onset. This translated to a relative reduction of 29% (P = .002). The overall utilization of feeding tubes was reduced among those who received avasopasem. The rates of use were reduced by 21%, and the rates of narcotics use for oral mucositis pain was 13%.

Galera Therapeutics has stated that they intend to request a Type A meeting to better understand the FDA’s decision and discuss next steps for NDA resubmission.¹

References

1. Galera Receives Complete Response Letter from U.S. FDA for Avasopasem Manganese. News release. Galera Therapeutics. August 9, 2023. Accessed August 9, 2023. https://investors.galeratx.com/news-releases/news-release-details/galera-receives-complete-response-letter-us-fda-avasopasem
2. Cullen E, Brown H, Carringer J, Amado A, Pitre L, and Anderson C. ROMAN: phase 3 trial of avasopasem manganese (GC4419) for SOM (SOM) in patients receiving chemoradiotherapy (CRT) for locally advanced head and neck cancer (LAHNC). Paper presented at: 48th Annual Oncology Nursing Society Congress; April 26-30, 2023; San Antonio, TX. Accessed June 7, 2023. https://ons.confex.com/ons/2023/meetingapp.cgi/Paper/12846