DermX: Topical Protector Against Radiation Dermatitis

DermX：针对放射性皮炎的局部保护剂

• 批准号: 7125935
• 负责人: ALLEN THUNBERG
• 金额: $ 21.52万
• 依托单位: PROCERTUS BIOPHARM, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-13 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7125935
• 关键词: athymic mouse; chemoprevention; cytoprotection; drug design /synthesis /production; drug screening /evaluation; laboratory rat; miniature swine; neoplasm /cancer radiation therapy; nonhuman therapy evaluation; pharmacokinetics; polyamines; radioprotective agents; therapy adverse effect; topical drug application

Numerous clinical studies have described the negative impact of radiotherapy-induced dermatitis on cancer patients during and after their 5-6 week course of radiotherapy. Virtually all patients develop at least a mild dermatitis, and for almost half it's a painful side effect lasting weeks. There can be scarring, limitations on more aggressive radiotherapy, and can result in patients quitting radiotherapy, with a significant effect upon tumor recurrence. There are no products on the market that prevent or treat this dermatitis. ProCertus, an early-stage biotech company, has developed a topically-applied small molecule drug for a product, DermX, that confers complete protection against the Grade 1->4 dermatitis seen in a rodent radiodermatitis model, a model that closely reflects the human experience. Based upon market analysis, ProCertus has concluded that a topical preventive for radiodermatitis would be well-received by cancer patients, and yield annual revenues in the range of $250 million. A DermX product would reduce radiotherapy-associated pain, could potentially enable more aggressive radiotherapy where dermatitis is dose-limiting, and could reduce the drop-out rate late in radiotherapy courses. Phase II funds will enable us to address the key, remaining issues in DermX scientific development, which are: i) ensure that topicallyapplied DermX does not affect external beam radiation killing of tumor cell xenografts in nude mice, ii) optimize a topical delivery vehicle that enables full radioprotection of skin stem cells while allowing insignificant levels of DermX active agent to enter systemic circulation, and iii) complete cGMP-certified batch synthesis of DermX that is required for studies prior to filing for its Investigational New Drug (IND) status. At the end of this Phase II project, ProCertus envisions a DermX product ready for clinical trials that: i) is a topical solution devoid of systemic side effects, ii) is applied 1-2 times in the 30 min before radiotherapy, and iii) is expected to prevent the Grade 1-4 dermatitis normally experienced by radiotherapy patients.

许多临床研究已经描述了放射治疗引起的皮炎对癌症患者在放射治疗过程中和治疗后5-6周的负面影响。几乎所有的患者都至少会出现轻微的皮炎，而且几乎有一半的患者会出现持续数周的疼痛副作用。可能会形成疤痕，限制更具侵袭性的放射治疗，并可能导致患者退出放射治疗，对肿瘤复发有显著影响。市场上没有预防或治疗这种皮炎的产品。 早期生物技术公司ProCertus为一种名为DermX的产品开发了一种局部应用的小分子药物，该药物可以完全预防啮齿动物放射性皮炎模型中出现的1-4级皮炎，这种模型与人类的经验密切相关。根据市场分析，ProCertus得出的结论是，一种局部预防放射性皮炎的药物将受到癌症患者的欢迎，年收入在2.5亿美元左右。一种DermX产品将减少放射相关的疼痛，可能会在皮炎剂量有限的情况下实现更具侵略性的放射治疗， 并且可以降低放射治疗疗程后期的辍学率。第二阶段的资金将使我们能够 解决DermX科学开发中的关键、仍然存在的问题，即：i)确保局部应用的DermX不影响外照射对裸鼠移植瘤细胞的杀伤作用，ii)优化一种局部给药载体，使其能够对皮肤干细胞进行全面辐射防护，同时允许无显著水平的DermX激活剂进入全身循环，以及iii)完成经cGMP认证的批量合成DermX，该合成是在申请其研究新药(IND)状态之前进行研究所需的。 在这一第二阶段项目结束时，ProCertus设想了一种可用于临床试验的DermX产品：i)是一种没有全身副作用的局部解决方案，ii)在放射治疗前30分钟内使用1-2次，iii)有望预防放射治疗患者通常经历的1-4级皮炎。