The FDA has issued a complete response letter to the new drug application seeking the approval of avasopasem manganese as a treatment for radiotherapy-induced severe oral mucositis in patients with head and neck cancer undergoing standard-of-care treatment.
The FDA has issued a complete response letter (CRL) to 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 undergoing standard-of-care treatment.1
The regulatory agency ruled that data from the phase 3 ROMAN (NCT03689712) and phase 2b GT-201 (NCT02508389) trials did not sufficiently demonstrate substantial evidence of avasopasem’s efficacy and safety in reducing SOM in this patient population, and an additional clinical trial will be needed for resubmission of the NDA, according to an announcement from Galera Therapeutics.
Following the CRL, the company shared that they plan on requesting a Type A meeting with the FDA to further discuss the decision and next steps for supporting resubmission of the NDA. They will also explore potential partnerships for the continued development of avasopasem and rucosopasem manganese (GC4711).
“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.”
The initial BLA was supported by data from 678 patients enrolled across ROMAN and GT-201. In GT-201, patients treated with avasopasem experienced a median duration of SOM of 1.5 days compared with 19 days for those treated with placebo (P = .024).2 Furthermore, the rates of SOM were 43% and 65% in the avasopasem and placebo arms, respectively (P = .009). The rates of grade 4 SOM were 16% and 30%, respectively (P = .045).
In the confirmatory ROMAN study, 54% of patients treated with avasopasem (n = 241) and intensity-modulated radiation therapy (IMRT) experienced SOM vs 64% of those given placebo (n = 166; relative risk, 0.84; P = .045).3 Grade 4 SOM was reported in 24% of patients in the avasopasem arm compared with 33% of those in the placebo arm (P = .052). The median duration of SOM was 8 days for avasopasem compared with 18 days for placebo (P = .002), and the mean number of days of grade 4 SOM was 5.5 for avasopasem and 7.2 for placebo (P = .143).
The randomized, double-blind, placebo-controlled GT-201 trial enrolled 223 patients with locally advanced oral cavity or oropharynx cancer who planned to be treated with definitive or postoperative IMRT.2 Patients received standard-of-care radiotherapy plus cisplatin and were randomly assigned 1:1:1 to receive 30 mg of avasopasem (n = 73), 90 mg of avasopasem (n = 76), or placebo (n = 74) by infusion prior to each fraction of radiation.
The primary end point was duration of SOM in the avasopasem cohorts compared with the placebo cohort.
Regarding safety, no significant toxicities specific to avasopasem were observed, and there was no increase in the known toxicities of IMRT plus cisplatin.
ROMAN was a randomized, double-blind, placebo-controlled trial that included 455 patients with locally advanced, squamous cell oral cavity or oropharynx cancer who were eligible for treatment with 7 weeks of IMRT plus cisplatin.3 Patients were randomly assigned 3:2 to receive 90 mg of avasopasem or placebo on the days they received radiation for 7 weeks.
The primary end point was the incidence of SOM through IMRT. Secondary end points included the total days of SOM and the incidence and total number of days of grade 4 SOM.
Safety data showed avasopasem was generally well tolerated, and findings were consisting with the phase 2 results.