Avasopasem Receives Priority Review for Radiotherapy-Induced Severe Oral Mucositis

The FDA has granted avasopasem a priority review for severe oral mucositis in patients with head and neck cancer who are receiving radiotherapy.

The FDA has granted priority review to the new drug application (NDA) for avasopasem manganese (GC4419) as a treatment for radiotherapy-induced severe oral mucositis (SOM) in patients with head and neck cancer undergoing standard-of-care treatment. The Prescription Drug User Fee Act (PDUFA) target date is August 9, 2023.1

Two trials supported the New Drug Application (NDA) for avasopasem. These were the phase 3 ROMAN (NCT03689712) and Phase 2b GT-201 trials (NCT02508389), both of which were randomized, double-blind, and placebo-controlled trials which, together, enrolled 678 participants.2,3 In both trials, avasopasem was found to lead to a meaningful reduction in incidence and numbers of days with SOM, decreased SOM severity, and a delayed onset time for SOM. In addition, follow-up data assessing patients’ renal function through 12 months post radiotherapy and avasopasem suggest that the treatment may delivers a meaningful reduction in long-term loss of kidney function with concurrent cisplatin.1


ROMAN enrolled a total of 455 patients with locally advanced HNC who were receiving 7 weeks of standard-of-care radiotherapy plus cisplatin.2 These patients were then randomly assigned 3:2 to receive either 90-mg of avasopasem or placebo (both administrated via infusion) on the same day as their radiation treatment.

Findings from the trial, which were presented during the 2022 ASCO Annual Meeting, showed that avasopasem significantly reduced incidence of severe oral mucositis across all intensity-modulated radiation therapy (IMRT) landmarks. Specifically, through IMRT the incidence rate was 54% with avasopasem compared with 64% with placebo (relative risk [RR], 0.84; P = .045) meeting the trial’s primary end point.

In addition, treatment with avasopasem prior to IMRT led to a 56% reduction in the median days of oral mucositis (18 vs 8 days, respectively; P =.002), a 27% reduction in grade 4 incidence (33% vs 24%, respectively; P = .052), and a 24% reduction in the mean number of days of grade 4 incidence (7.2 vs 5.5 days, respectively; P = .143).

According to investigators, avasopasem was tolerable for patients compared with placebo. The adverse event profile was considered consistent with what would be expected with a group of patients receiving standard-of-care radiotherapy.

Moreover, one-year post follow-up, the patients who received avasopasem in combination with the standard-of-care regimen (radiotherapy plus cisplatin) reported comparable tumor outcomes and overall survival rates of those in the placebo, suggesting that the treatment protected patients from SOM without compromising their overall treatment efficacy with chemoradiotherapy.

2b GT-201 Trial

The GT-201 trial (GTI-4419-201) enrolled a total of 223 patients to be randomly assigned 1:1;1 to receive either 30 mg or 90 mg of avasopasem or placebo by infusion on the days they received radiation.3 Like with the ROMAN trial, all enrolled patients were receiving 7 weeks of standard-of-care radiotherapy plus cisplatin.

Again, in this trial, the SOM duration was significantly reduced, from 19 days to 1.5 days (P = .024). The rate of SOM incidence between placebo and 90-mg dose intervention arm were 65% vs 43% (P = .009) and the rate of grade 4 incidence was knocked down to 16% from 30% (P = .045). Modest improvements were also observed among those who received the 30-mg dose. No specific increase of toxicities was observed in this trial.

Potential Implications for Practice

Radiotherapy is considered standard-of-care for patients with head-and-neck cancer, however, SOM is a common toxicity associated with this treatment.1 SOM is characterized by acute inflammation or mucus membranes in the mouth and throat and can prevent a patient from eating solid foods or drinking liquids. Consequently, this toxicity can lead to hospitalization or surgical placement of a feeding tube to maintain nutrition and hydration.

It is estimated that 42,00 patients with head and neck cancer will receive radiotherapy; 70% of whom are anticipated to develop SOM during their treatment. However, there are currently no FDA-approved agents to mitigate SOM patients with head and neck cancers.

“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, noted in a news release announcing the priority review.

“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,” he concluded.


  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 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):6005. doi:10.1200/JCO.2022.40.16_suppl.6005
  3. 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

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