A Phase 2, randomized, double-blind, 4-arm, multicenter study to demonstrate the efficacy and safety of topical dosage formulations of a prescription drug product for actinic keratosis

PROJECT SUMMARY / ABSTRACT Acinic Keratoses (AK) are premalignant skin lesions with the potential to develop into Cutaneous Squamous cell Carcinoma (CSCC), which is the second most common type of cancer and when metastatic has a mortality rate that is higher than melanoma. There is a high unmet need for topical AK medications with shorter treatment durations and enhanced efficacy that can eradicate AK and treat the surrounding cancerized field. The Product of this SBIR will be a Food and Drug Administration approved fixed dose combination cream containing calcipotriol (CPO) and 5-fluorouracil (5-FU) as a treatment for AK in immunocompetent patients. Technological Innovation: Topical co-administration of CPO / 5-FU eradicates AKs by activating CD4+ T cell dominated immunity, an upstream activator of the adaptive immune response, which then recruits an array of downstream effector cells to block CSCC development. The Long-Term Goal is the registration of the SBIR product, which directly addresses the mission of the National Cancer Institute by harnessing the power of the immune system to treat AKs and prevent CSCC. Phase I SBIR Equivalent Studies demonstrated the clinical and commercial feasibility of the PHD technology for AK treatment. Successfully completed randomized (n=130) and open label clinical studies (n=18) demonstrated the feasibility of the CPO / 5-FU combination as the best-in-class treatment for AK and the only product ever reported to reduce the risk of CSCC development at 3-years post treatment. The high impact of the published data has resulted in the National Comprehensive Cancer Network and the American Academy of Dermatology recommending CPO / 5-FU as a treatment for AK. Market research demonstrated prescriber and patient enthusiasm for the PHD product and confirmed that health insurance companies will provide broad coverage to beneficiaries at a price that will generate meaningful revenues for the company. Specific Aim 1. Complete a Phase 2, Randomized, Double-blind, 4-Arm, Multicenter Study to Demonstrate the Efficacy and Safety of Topical Dosage Formulations of CPO plus 5-FU for the treatment of AK. Phase II Objectives: Conduct a Phase 2 clinical trial to assess the efficacy and safety of topical dosage formulations containing two different concentrations of CPO plus 5-FU in 160 AK patients. Expected Outcomes: 5-FU / CPO is expected to be well-tolerated and significantly more efficacious than 5-FU monotherapy and placebo. The data will enable dose selection and design of the Phase 3 registrational studies. Commercial Opportunity: The target customer will be dermatologists and peak revenues of $285 mil are projected at the lowest probable list price, with 93% of patients paying ≤ $25 out-of-pocket.