Severe oral mucositis (SOM) is induced by radiation treatment and is the most frequent major radiation-induced side effect observed in patients with head and neck cancer (HNC). SOM induces intense oral pain and dysphagia and limits a patient's ability to eat and drink, which can lead to severe weight loss and a requirement for enteral or parenteral nutritional support. Patients that develop SOM are often hospitalized, and symptoms can force patients to stop cancer treatment for an undefined period of time or terminate early, thus reducing cancer treatment efficacy (Elting et al., 2008; Vera-Llonch et al., 2006). Thus, SOM impacts both quality of life and clinical outcomes in HNC patients. Currently, there are no FDA-approved preventive or therapeutic options for patients that develop radiation-induced SOM. Only symptomatic treatments such as opioids and mouthwashes are currently considered as part of the standard of care for this indication.

The global incidence of HNC was approximately 690,000 cases in 2012 (Globocan 2012; Gupta, 2016). The incidence of HNC in the U.S. was approximately 63,000 cases in 2017 (cancer.net) and is projected to increase to more than 93,000 new cases by 2030 (Gupta et al., 2016). A similar increase is also predicted in the European Union (EU) Five (France, Germany, Italy, Spain and the United Kingdom).

These projections include all HNC patients, regardless of the anatomic location of their disease. However, the most rapidly growing sub-population of HNC are patients with oropharyngeal cancer (OPC) (Chaturvedi et al., 2011; Ramqvist et al., 2010). The oropharynx is comprised largely of immune tissue and includes the soft palate, the base (rear one third) of the tongue, and the tonsils. In the U.S., the incidence of OPC is approaching 70% of all HNC, the majority of which (approximately 70%) is affected by the human papilloma virus (HPV+) (Chaturvedi et al., 2011; Jordan et al., 2012; Gooi et al., 2016). The incidence of OPC is also increasing in the rest of the world (>30% of HNC) (Taberna et al., 2017), with >50% of all OPC being HPV+ (Gupta et al., 2016; Fakhry et al., 2015).

Recent data (Vatca et al., 2014) have demonstrated that HPV+ OPC patients have a 6.9-fold increased risk of developing SOM during radiation treatment, and that onset of SOM occurs sooner than in HPV- OPC patients. These observations suggest that HPV+ OPC patients may be more likely to benefit from Validive treatment than other HNC patients. The incidence of HPV+ OPC has outpaced the incidence of HPV- HNC by 4-5-fold over the past decade (Chaturvedi et al., 2011; Castellsagué et al., 2017). We project that this trend will continue for at least the next 20-25 years (another generation) in the U.S. based on the predicted increase in high-risk oral HPV infections due to the lack of adequate use of HPV vaccinations in children (Castellsagué et al., 2017). Thus, the HPV+ OPC population could be a driver of market growth for Validive, and also represents a potentially molecularly defined population for the clinical development of this drug (Taberna et al., 2017; Castellsagué et al., 2017).

Phase 2 Data

Analysis of a completed randomized, placebo controlled Phase 2 trial comparing the effects of Validive to placebo in reducing the incidence of SOM supports further development of Validive in oropharyngeal cancer.

Phase 2 Data