The FDA has granted a fast-track designation for RRx-001 and accepted the investigational new drug application for a phase 2b trial of severe oral mucositis in chemotherapy- and radiation-treated patients with head & neck cancer.
The FDA granted a fast-track designation to RRx-001 for the prevention of severe oral mucositis in chemotherapy- and radiation-treated patients with head and neck cancer, according to EpicentRx, Inc.1
The FDA also accepted the investigational new drug application that will commence the follow-on, phase 2b trial, of KEVLARx, in this same patient population.
"The fast-track designation is great news for EpicentRx, and it puts us one step closer to a potential treatment for this critical unmet need of oral mucositis with RRx-001," said Tony Reid, MD, chief executive officer of EpicentRx, in the press release.
RRx-001 is a direct NLRP3 inhibitor and Nrf2 upregulator that has anti-inflammatory and antioxidant properties. Currently, the agent is being investigated in a phase 3 trial (NCT05566041) for the treatment of patients with small cell lung cancer (SCLC). Additionally, RRx-001 is under development as a medical countermeasure for nuclear and radiological emergencies, as well as for patients with neurodegenerative diseases, including Parkinson's and amyotrophic lateral sclerosis/motor neurone disease.
The potential of RRx-001 as a protective agent for non-cancer, or normal cells, is linked with its abilities to activity as an NLRP3 inflammasome inhibitor and as an activator of the Nrf2 antioxidant transcription factor.
The agent was previously studied in the phase 2 PREVLAR trial (NCT03515538). According to a study published in International Journal of Radiation Oncology, Biology and Physics, data from PREVLAR demonstrated that RRx-001 protects against severe oral mucositis in patients receiving radiation and chemotherapy for head and neck cancer.2
PREVLAR was a multi-institutional, randomized trial that evaluated the safety and efficacy of 3 dosing schedules of RRx-001 to protect against the development of oral mucositis in patients receiving concomitant chemoradiation for oral and oropharyngeal cancers.
A total of 53 patients were enrolled in the trial, and 46 and 45 individuals contributed to the reported safety and efficacy data, respectively. Across all 3 active arms, RRx-001 was infused fully in 86% of patients and all 3 treatment cohorts of RRx-001 led to a similar or lower oral mucositis duration relative to control.3
Findings showed that pre-radiation RRx-001 alone led to favorable impacts in the incidence and duration of severe oral mucositis, and that the treatment was safe. Patients given treatment with RRx-001 responded no differently to their cancer compared with patients in a control arm when evaluated 2 years after they completed treatment with chemoradiation.
In arm 1, there was the lowest median duration of severe oral mucositis at 8.5 days vs 24 days in controls among patients who developed at least 1 day of severe oral mucositis. Additionally, no severe adverse events were attributed to the study drug.
The larger, phase 2, randomized study, KEVLARx, is planned to further assess the role of RRx-001 and determine how it works for the prevention of oral mucositis in first-line head and neck cancer.
"The results noted in PREVLAR suggest that RRx-001 may provide protection from severe radiation-associated mucositis with a dosing schedule that is highly desirable for both patients and radiation oncologists.I look forward to further study of this treatment in the subsequent KEVLAR study," said Stephen Sonis, MD, Harvard professor of oral medicine and member of the distinguished faculty of the Dana-Farber Cancer Institute, and co-author on the manuscript, in the press release.2