Avasopasem for the treatment of radiotherapy-induced severe oral mucositis

ABSTRACTIntroduction Oral mucositis (OM) remains a significant, highly symptomatic, disruptive side effect of radiation and concomitant chemoradiation therapy used for the treatment of squamous cell cancers of the head and neck. Despite its clinical and economic burden, implementation of an effective intervention has been elusive.Areas covered Increased understanding of the complexity of the biological basis for its pathogenesis has yielded potential druggable targets such as the mitigation of superoxide formation and oxidative stress. Avasopasem manganese is a selective superoxide dismutase mimetic being developed by Galera Therapeutics, which recently submitted a New Drug Application (NDA) to the FDA for a severe OM indication. This review describes the preclinical and clinical studies which led to, and supported the NDA, and assesses the potential utility of avasopasem clinically.Expert opinion Avasopasem manganese appears to effectively mitigate severe OM associated with concomitant chemoradiation used in the treatment of head and neck cancers, as well as cisplatin-associated renal toxicity in the absence of impairing tumor response.KEYWORDS: Oral mucositisradiationchemoradiationhead and neck canceravasopasem manganeseclinical development Article highlights Oral mucositis remains a common, significant, and treatment-limiting side effect of standard chemoradiation regimens used as therapy for squamous cell cancers of the head and neck.Oxidative stress is a critical component in the initiation of the biological events which precipitate in OM development.Avasopasem manganese, a superoxide dismutase mimetic, appears to effectively supplement naturally occurring antioxidant mechanism to favorably protect normal oral mucosa while not interfering with tumor cell radiosensitivity.Pre-clinical and clinical data have consistently indicated that avasopasem manganese is safe and effective in mitigating the course and incidence of severe mucositis associated with chemoradiation regimens.The requirement for intravenous administration in proximity to radiation administration could require infrastructure changes in high volume practices and/or coordination between radiotherapy sites and infusion centers.Avasopasem appears to be positioned to be a breakthrough intervention for an otherwise unmanageable complication of chemoradiation therapy.Declaration of interestDr Sonis is an employee of Biomodels, LLC and Primary Endpoint Solutions, LLC. Both companies assist industry, government, and academics to study and enable drugs, biologicals, and devices to treat patients for a variety of indications including cancer and the side effects and toxicities of its treatment. Both companies have done contract work for Galera. Dr Sonis does not have equity in any of the companies with which either organization works.The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.AcknowledgmentsWe thank Robert Beardsley for providing historical background on the development of avasopasem manganese.Additional informationFundingThis paper was not funded.