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

项目总结/摘要 腺泡性角化病（AK）是一种具有发展为皮肤鳞状细胞的潜能的癌前病变 癌（CSCC），这是第二种最常见的癌症类型，当转移时具有死亡率 比黑色素瘤高治疗时间较短的局部AK药物的需求高度未满足 持续时间和增强的功效，可以根除AK并治疗周围的癌变区域。 本SBIR的产品将是食品和药物管理局批准的固定剂量组合霜 含有卡泊三醇（CPO）和5-氟尿嘧啶（5-FU）的组合物作为免疫活性患者中AK的治疗。 技术创新：CPO / 5-FU局部联合给药通过激活CD 4 + T细胞根除AK 支配性免疫，适应性免疫反应的上游激活剂，然后招募一系列 下游效应细胞以阻断CSCC发展。 长期目标是SBIR产品的注册，它直接解决了国家的使命。 癌症研究所通过利用免疫系统的力量来治疗AK和预防CSCC。 I期SBIR等效研究证明了PHD技术的临床和商业可行性 AK治疗。成功完成随机（n=130）和开放标签临床研究（n=18） 证明了CPO / 5-FU组合作为AK的同类最佳治疗和唯一治疗的可行性。 据报道，该产品可降低治疗后3年发生CSCC的风险。的高影响， 已发表的数据导致国家综合癌症网络和美国癌症研究院 皮肤科推荐CPO / 5-FU作为AK的治疗。市场研究表明，开处方者和 患者对PHD产品的热情，并确认健康保险公司将提供广泛的 以能够为公司带来可观收入的价格向受益人提供保险。 具体目标1。完成一项II期、随机、双盲、4组、多中心研究，以证明 CPO +5-FU局部给药制剂治疗AK的有效性和安全性。 II期目的：进行II期临床试验，以评估局部剂量的有效性和安全性 在160名AK患者中，使用含有两种不同浓度的CPO加5-FU的制剂。 预期结局：5-FU / CPO预期耐受性良好，且显著优于5-FU 单一疗法和安慰剂。这些数据将有助于剂量选择和III期注册研究的设计。 商业机会：目标客户将是皮肤科医生，最高收入为2.85亿美元。 预计在最低可能的标价，93%的患者支付≤ 25美元的自付。

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.