The FDA has issued a complete response letter in response to the new drug application (NDA) for avasopasem manganese (GC4419), intended for treating radiotherapy-induced severe oral mucositis (SOM) in patients with head and neck cancer undergoing standard-of-care treatment.
Earlier, the FDA had granted a priority review to the NDA, primarily based on data from the Phase IIb GT-201 (NCT02508389) and Phase III ROMAN (NCT03689712) trials. These trials indicated a notable reduction in the median duration of SOM at 1.5 days compared to the 19 days with placebo (P = 0.024) in the Phase II trial, and in the Phase III study, the incidence rate was lowered to 54% versus 64% (relative risk, 0.84; P = 0.045). Despite this, the complete response letter stated that the trial data didn’t provide sufficient evidence to establish the efficacy and safety of avasopasem in reducing SOM. The FDA indicated that another clinical trial would be necessary before submitting the NDA.
Galera Therapeutics, the developer of avasopasem, announced in a press release their plans for an upcoming Type A meeting with the FDA to discuss the path forward for the drug. The company also intends to form partnerships with other firms to continue the development of both avasopasem and another drug, rucosopasem manganese (GC4711).
“This response from the FDA is deeply disappointing for Galera and for patients who suffer from severe oral mucositis. 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. As we explore a potential approval path for avasopasem, we are taking decisive actions to extend our cash runway. Unfortunately, this necessitates reducing our workforce by approximately 70%. We are grateful for the many contributions our talented team has made over the years and their commitment to avasopasem.”
– Mel Sorensen, M.D., Galera’s President and CEO
Avasopasem, a selective small molecule dismutase mimetic, is designed to protect normal cells from radiation therapy by converting radiation-induced superoxide into hydrogen peroxide. The Phase II study validated this approach as it effectively safeguarded patients from radiotherapy-induced SOM without compromising the treatment’s benefits for those with head and neck cancer.
The GT-201 study enrolled 223 patients with locally advanced head and neck cancer who had received at least 7 weeks of standard-of-care radiotherapy plus cisplatin. After randomizing patients to receive 30 mg of avasopasem, 90 mg of avasopasem, or placebo, the study found that the 90 mg dose of the agent was optimal. This led to the ROMAN trial, which enrolled 455 patients and randomized them 3:2 to receive avasopasem or placebo. However, the primary endpoint of the ROMAN study was the cumulative incidence of SOM from the first intensity-modulated radiation therapy (IMRT) fraction until the end of the study treatment periods.
“We will continue our focus on completing enrollment of our rucosopasem GRECO trials. Our GRECO-2 trial is a 220-patient trial in locally advanced pancreatic cancer intended to build upon the positive results observed in our placebo-controlled pilot trial, where we saw meaningful improvements in multiple endpoints including overall survival and tumor outcomes. There is an urgent need for novel therapies to extend survival in patients with pancreatic cancer, and we believe rucosopasem’s unique mechanism of action in combination with SBRT could offer a transformative treatment option.”
– Mel Sorensen, M.D., Galera’s President and CEO
Results from the ROMAN study indicated that administering avasopasem prior to IMRT led to a 56% reduction in the median duration of SOM compared to placebo at 8 days versus 18 days (P = 0.002). Additionally, patients had a 27% reduction in the incidence of grade 4 SOM (P = 0.052) and a 34% reduction in the mean number of days of grade 4 SOM incidence at 7.2 days versus 5.5 days (P = 0.143).
As of June 30, 2023, Galera had $38.8 million in cash, cash equivalents and marketable securities, according to its preliminary estimate. This number is not final and may change after the Company completes its financial closing procedures. The Company will submit its Quarterly Report on Form 10-Q for the quarter that ended on June 30, 2023 on August 14, 2023. The Company now anticipates that its current cash will last until the second quarter of 2024.
