On December 12, 2022 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, reported the submission of its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for avasopasem for radiotherapy-induced severe oral mucositis (SOM) in patients with head and neck cancer (HNC) undergoing standard-of-care treatment (Press release, Galera Therapeutics, DEC 12, 2022, View Source [SID1234625072]). The FDA has granted Fast Track and Breakthrough Therapy designations to avasopasem for the reduction of SOM induced by radiotherapy. SOM is characterized by the inability to eat solid food or drink liquids and may require the surgical placement of feeding tubes to maintain nutrition and hydration. There are currently no FDA-approved drugs to reduce SOM for these patients.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"With submission of this NDA, we achieved an important milestone towards our goal of transforming radiotherapy, potentially bringing patients with HNC the first approved drug for SOM and relief from its tremendous burden," said Mel Sorensen, M.D., President and Chief Executive Officer of Galera Therapeutics. "Approximately 42,000 patients with HNC undergo standard-of-care radiotherapy every year in the U.S. and are at risk of developing SOM. Our two rigorous, placebo-controlled trials which enrolled nearly 700 patients give us confidence that avasopasem has the potential to provide meaningful clinical benefit for patients by reducing SOM incidence, days, and severity while also delaying its onset. We look forward to working closely with the FDA during the review process."

Dr. Sorensen continued, "Further, the reduction in cisplatin-related chronic kidney disease in patients treated with avasopasem reported in October may offer added clinical benefit to the large number of patients with HNC who receive cisplatin with their radiotherapy."

The NDA is supported by the randomized, double-blinded, placebo-controlled Phase 3 ROMAN and Phase 2b GT-201 trials which enrolled a total of 678 patients. 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. Avasopasem also showed clinically meaningful reductions in severity of SOM (Grade 4 incidence) compared to placebo. Exploratory analyses, such as time to SOM onset and SOM incidence at various landmarks of radiotherapy delivered, further demonstrated the clinical benefit of avasopasem in reducing the burden of SOM. Avasopasem was generally well tolerated compared to placebo. Overall, the adverse event (AE) incidences noted in the clinical trials 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 chemoradiation therapy. In addition, a prospectively defined exploratory analysis looking at renal function through 12 months follow-up showed that avasopasem reduced cisplatin-induced chronic kidney disease by 50%.

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 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) was also observed. Exploratory analyses, such as time to SOM onset and SOM incidence at various landmarks of radiotherapy delivered, also demonstrated the clinical benefit of avasopasem in reducing the burden of SOM, along with a reduction in long-term loss of kidney function associated with concurrent cisplatin. Avasopasem was generally well tolerated compared to placebo.

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.

About Severe Oral Mucositis (SOM)

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. In patients with head and neck cancer, radiotherapy is a mainstay of treatment. Approximately 70 percent of patients receiving radiotherapy for head and neck cancer develop SOM, defined by the inability to eat solid food or drink liquids. 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 small molecule 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.