Avasopasem manganese (GC4419) is an investigational selective dismutase mimetic drug in development as a radioprotector in combination with radiation therapy (RT), with the goal to reduce side effects from radiation therapy.

  • In preclinical studies, our selective dismutase mimetics significantly reduced immediate and long-term radiation damage to normal tissue in a variety of organs.
  • Avasopasem received Breakthrough Therapy and Fast Track Designations from the U.S. Food and Drug Administration for the reduction of the incidence and severity of radiation induced oral mucositis in head and neck cancer.
  • Avasopasem has completed two randomized trials, both of which met the primary endpoint, to evaluate reduction of severe oral mucositis in patients with head and neck cancer undergoing radiation therapy.1-2

GT-201 Clinical Trial

Avasopasem was studied in a randomized, double-blinded, placebo-controlled 223-patient trial (GT-201) at 44 North American sites. In the trial, avasopasem met the primary endpoint by demonstrating a 92% reduction in median number of days of SOM in the 90 mg treatment arm as compared to placebo.2

 

GT-201 Randomized Clinical Trial results

 

The overall adverse event profile in each of the avasopasem arms was comparable to that in the placebo arm and seemed consistent with the known toxicities of IMRT plus cisplatin when either severe events or events of mild severity grades or grades 3 or greater were considered.  Adverse effects that appeared related to avasopasem were limited to transient, mild-to moderate decreases in blood pressure.2

In this trial, tumor outcomes were maintained at one and two years.3

Anderson CM, 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 cancerJ Clin Oncol. 2019;37:3256-3265.

 

GTI-4419-301 (ROMAN) Phase 3 Clinical Trial

Avasopasem was also studied in a randomized, double-blinded, placebo-controlled 455-patient Phase 3 clinical trial (GTI-4419-301) at 97 North American sites.  In this trial, avasopasem met the primary endpoint by demonstrating a statistically significant reduction in the incidence of SOM (p = 0.045), as well as in the number of days of SOM (p = 0.002).

Results from ROMAN Phase 3

Avasopasem was generally well tolerated. Adverse event frequencies were comparable between treatment groups without clear AVA-specific toxicity or increase in cisplatin-attributable toxicity. The most common adverse events in both arms were lymphopenia, nausea, and fatigue, and the most common severe (grade ≥3) adverse events were lymphopenia, leukopenia, and neutropenia.4

Anderson CM, Lee C, 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). Presented at ASCO Annual Meeting, June 3, 2022.

Galera is on track to file an NDA for avasopasem for the treatment of radiotherapy-induced severe oral mucositis (SOM) in patients with locally advanced head and neck cancer with the U.S. Food and Drug Administration (FDA) by the end of 2022.


References:

  1. Anderson CM, Sonis ST, Lee CM, et al. Phase 1b/2a Trial of the Superoxide Dismutase Mimetic GC4419 to Reduce Chemoradiotherapy-Induced Oral Mucositis in Patients With Oral Cavity or Oropharyngeal Carcinoma. Int J Radiat Oncol. Published Online October 16, 2017.
  2. Anderson CM, 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;37:3256-3265.
  3. Anderson CM, Lee CM, Saunders D, et al. Tumor outcomes of 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. Presented at: Multidisciplinary Head and Neck Cancer Symposium, February 27-29, 2020.
  4. Anderson CM, Lee C, 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). Presented at ASCO Annual Meeting, June 3, 2022.

 

Investigational Drug – Not for Commercial Distribution