Galera Announces FDA Acceptance and Priority Review of Avasopasem NDA for Radiotherapy-Induced Severe Oral Mucositis

PDUFA target date of August 9, 2023

Avasopasem would be first drug approved for SOM in patients with head and neck cancer

MALVERN, Pa., Feb. 15, 2023 (GLOBE NEWSWIRE) -- Galera Therapeutics, Inc. (Nasdaq: GRTX), a clinical-stage biopharmaceutical company focused on developing and commercializing a pipeline of novel, proprietary therapeutics that have the potential to transform radiotherapy in cancer, today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing and granted priority review to the New Drug Application (NDA) for avasopasem manganese for radiotherapy (RT)-induced severe oral mucositis (SOM) in patients with head and neck cancer (HNC) undergoing standard-of-care treatment. There are currently no FDA-approved drugs to reduce SOM for these patients. With the 6-month priority review designation, the Prescription Drug User Fee Act (PDUFA) target date assigned by the FDA for this NDA is August 9, 2023. The FDA indicated in its acceptance of filing letter that it is not planning to hold an advisory committee meeting on the application.

The FDA previously granted Breakthrough Therapy and Fast Track designations to avasopasem for the reduction of SOM induced by RT.

"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,” said Mel Sorensen, M.D., President and Chief Executive Officer of Galera Therapeutics.

Dr. Sorensen continued: “Each year approximately 42,000 U.S. patients with HNC are at high risk of developing SOM as a part of their cancer treatment. The impact of SOM, the most burdensome toxicity of standard-of-care RT, on a patient’s physical and psychological wellbeing is substantial, particularly when hospitalization and surgical placement of feeding tubes to maintain nutrition and hydration are required. In some patients, SOM is so debilitating that they may delay and/or discontinue potentially curative RT, undermining their care. 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.”

The NDA is supported by two randomized, double-blind, placebo-controlled trials (Phase 3 ROMAN and Phase 2b GT-201), which enrolled a total of 678 patients. Both trials demonstrated clinically meaningful reductions across key measures of patients’ SOM burden, including decreasing the incidence and number of days of SOM, decreasing the severity (incidence of Grade 4 oral mucositis, the inability to eat or drink), and delaying the time to SOM onset. In addition, follow-up data that was collected on renal function through 12 months post administration of RT and avasopasem point to another clinically meaningful benefit for these patients, most of whom receive cisplatin chemotherapy as part of their care. In the ROMAN trial, results on a pre-defined exploratory endpoint showed that avasopasem reduced cisplatin-induced chronic kidney disease by half at one year.  

In both trials, the reported side effects were consistent with those caused by RT and cisplatin, other than some increases in rates of hypotension and mild nausea with avasopasem. There were nominal decreases in the rates of some side effects associated with RT or with cisplatin among avasopasem patients in the combined trials, such as oropharyngeal pain, radiation skin injury, tinnitus, and acute kidney injury.

After long-term follow-up in both trials, patients treated with avasopasem in combination with the standard-of-care regimen (RT plus cisplatin) demonstrated comparable tumor outcomes and overall survival to patients in the placebo arm, showing that avasopasem protected HNC patients from SOM without affecting the treatment benefit of standard-of-care chemoradiotherapy.

About the Phase 3 Roman Trial

The Phase 3 ROMAN trial (GTI-4419-301) was a randomized, double-blind, placebo-controlled trial in 455 patients designed to evaluate the ability of avasopasem to reduce radiation-induced SOM in patients with locally advanced HNC, receiving seven weeks of standard-of-care radiotherapy plus cisplatin. Patients were randomized to one of the two treatment groups (3:2) to receive 90 mg of avasopasem or placebo by infusion on the days they receive their radiation treatment.

Results from the 455-patient ROMAN trial demonstrated a clinically meaningful reduction in patients’ SOM burden across multiple endpoints, with statistically significant reductions on the primary endpoint of incidence of SOM and the secondary endpoint of number of days of SOM, more than halving the median number of days a patient suffered SOM. Meaningful reduction in the number of patients who developed the most severe form of SOM (Grade 4, the inability to eat or drink) was also observed. Exploratory analyses, such as time to SOM onset and SOM incidence at various landmarks of cumulative radiotherapy delivered, also demonstrated the clinical benefit of avasopasem in reducing the burden of SOM, along with a meaningful reduction in long-term loss of kidney function associated with concurrent cisplatin.

Avasopasem was generally well tolerated compared to placebo. Overall, the adverse event (AE) incidences were consistent with the interpretation that avasopasem was not associated with a clinically meaningful increase in the AE profile expected for the target patient population receiving standard-of-care radiotherapy.

After one-year follow-up in the ROMAN trial, patients treated with avasopasem in combination with the standard-of-care regimen (RT plus cisplatin) demonstrated comparable tumor outcomes and overall survival to patients in the placebo arm, showing that avasopasem protected HNC patients from SOM without affecting the treatment benefit of standard-of-care chemoradiotherapy.

About the Phase 2b GT-201 Trial

The GT-201 trial (GTI-4419-201) was a randomized, double-blind, placebo-controlled trial in 223 patients designed to evaluate the ability of avasopasem to reduce radiation-induced SOM in patients with locally advanced HNC, receiving seven weeks of standard-of-care radiotherapy plus cisplatin. Patients were randomized to one of the three treatment groups (1:1:1) to receive either 30 mg or 90 mg of avasopasem or placebo by infusion on the days they receive their radiation treatment.

Results from the 223-patient Phase 2b trial demonstrated a meaningful reduction in patients’ SOM burden across multiple endpoints, with a statistically significant reduction on the primary endpoint of number of days of SOM in the 90 mg avasopasem arm compared to placebo. Avasopasem also resulted in clinically meaningful reductions in the incidence, severity (Grade 4 incidence), and onset of SOM compared to placebo. Avasopasem was generally well tolerated compared to placebo. The FDA granted Breakthrough Therapy designation to avasopasem for the reduction of SOM induced by radiotherapy, based on the positive results of the GT-201 trial.

Avasopasem was generally well tolerated compared to placebo. Overall, the adverse event (AE) incidences were consistent with the interpretation that avasopasem was not associated with a clinically meaningful increase in the AE profile expected for the target patient population receiving standard-of-care radiotherapy.

After two-year follow-up in the GT-201 trial, patients treated with avasopasem in combination with the standard-of-care regimen (RT plus cisplatin) demonstrated comparable tumor outcomes and overall survival to patients in the placebo arm, showing that avasopasem protected HNC patients from SOM without affecting the treatment benefit of standard-of-care chemoradiotherapy.

The FDA granted Breakthrough Therapy designation to avasopasem for the reduction of SOM induced by radiotherapy, based on the positive results of the GT-201 trial.

About Severe Oral Mucositis (SOM)

SOM, acute inflammation of mucus membranes in the mouth and throat that prevents a patient from eating solid food or drinking liquids, is a common and burdensome toxicity of radiotherapy, which is the standard-of-care treatment for head and neck cancer. Approximately 42,000 patients with head and neck cancer undergo standard-of-care radiotherapy every year in the U.S. and are at risk of experiencing SOM, and approximately 70 percent of patients will develop SOM during treatment. The impact on patients who develop SOM is substantial, particularly when hospitalization and/or surgical placement of feeding (PEG) tubes to maintain nutrition and hydration are required. SOM can adversely affect cancer treatment outcomes by causing interruptions in radiotherapy, which may compromise the otherwise good prognosis for tumor control in many of these patients. There is currently no drug approved to prevent or treat SOM for these patients.

About Avasopasem

Avasopasem manganese 90 mg (avasopasem, or GC4419) is a selective dismutase mimetic in development for the reduction of radiotherapy-induced severe oral mucositis (SOM) in patients with locally advanced head and neck cancer (HNC) and for the reduction of radiotherapy-induced esophagitis in patients with lung cancer. The FDA has granted Fast Track and Breakthrough Therapy designations to avasopasem for the reduction of SOM induced by radiotherapy. Avasopasem is currently under FDA priority review for radiotherapy-induced SOM in patients with HNC undergoing standard-of-care treatment.

About Galera Therapeutics

Galera Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing and commercializing a pipeline of novel, proprietary therapeutic candidates that have the potential to transform radiotherapy in cancer. Galera’s selective dismutase mimetic product candidate avasopasem manganese (avasopasem, or GC4419) is being developed for radiotherapy-induced toxicities. The Company’s second product candidate, rucosopasem manganese (rucosopasem, or GC4711), is in clinical-stage development to augment the anti-cancer efficacy of stereotactic body radiation therapy in patients with non-small cell lung cancer and locally advanced pancreatic cancer. Galera is headquartered in Malvern, PA. For more information, please visit www.galeratx.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding: the expectations surrounding the continued advancement of Galera’s product pipeline; the potential safety and efficacy of Galera’s product candidates and their regulatory and clinical development; the potential to obtain approval by the U.S. Food and Drug Administration for avasopasem for the treatment of radiotherapy-induced severe oral mucositis (SOM) in patients with locally advanced head and neck cancer at any time, including on or about August 9, 2023; the ability of avasopasem to provide meaningful clinical benefit to patients by reducing the number who develop SOM and how long they are afflicted with it; the ability of avasopasem to delay onset of SOM and decrease the number of patients who develop the most severe form of SOM; the potential of avasopasem to offer clinical benefit to a large number of patients with HNC who receive cisplatin; the clinical benefit in reducing the burden of SOM along with reduction in long-term loss of kidney function associated with concurrent cisplatin; the ability of avasopasem to protect HNC patients from SOM without affecting the treatment benefit of standard-of-care chemoradiotherapy; and the Company’s ability to achieve its goal of transforming radiotherapy in cancer treatment with its selective dismutase mimetics. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause Galera’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: Galera’s limited operating history; anticipating continued losses for the foreseeable future; needing substantial funding and the ability to raise capital; Galera’s dependence on avasopasem manganese (GC4419); uncertainties inherent in the conduct of clinical trials; difficulties or delays enrolling patients in clinical trials; the FDA’s acceptance of data from clinical trials outside the United States; undesirable side effects from Galera’s product candidates; risks relating to the regulatory approval process; failure to capitalize on more profitable product candidates or indications; ability to receive or maintain Breakthrough Therapy Designation or Fast Track Designation for product candidates; failure to obtain regulatory approval of product candidates in the United States or other jurisdictions; ongoing regulatory obligations and continued regulatory review; risks related to commercialization; risks related to competition; ability to retain key employees and manage growth; risks related to intellectual property; inability to maintain collaborations or the failure of these collaborations; Galera’s reliance on third parties; the possibility of system failures or security breaches; liability related to the privacy of health information obtained from clinical trials and product liability lawsuits; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; environmental, health and safety laws and regulations; the impact of the COVID-19 pandemic on Galera’s business and operations, including preclinical studies and clinical trials, and general economic conditions; risks related to ownership of Galera’s common stock; and significant costs as a result of operating as a public company. These and other important factors discussed under the caption “Risk Factors” in Galera’s Annual Report on Form 10-K for the year ended December 31, 2021 filed with the U.S. Securities and Exchange Commission (SEC), Galera’s Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2022, and Galera’s other filings with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any forward-looking statements speak only as of the date of this press release and are based on information available to Galera as of the date of this release, and Galera assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise.

Investor Contacts:
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