DermX: Topical Protector Against Radiation Dermatitis

DermX：针对放射性皮炎的局部保护剂

• 批准号: 6992390
• 负责人: ALLEN THUNBERG
• 金额: $ 111.77万
• 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 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6992390
• 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其5-6周的放射治疗过程期间和之后的负面影响。几乎所有的患者都会出现轻微的皮炎，几乎一半的患者会出现持续数周的疼痛副作用。可能会有疤痕，限制更积极的放射治疗，并可能导致患者放弃放射治疗，对肿瘤复发有显着影响。市场上没有预防或治疗这种皮炎的产品。 ProCertus是一家处于早期阶段的生物技术公司，已经为一种产品DermX开发了一种局部应用的小分子药物，该药物可以完全保护啮齿动物放射性皮炎模型中观察到的1->4级皮炎，该模型密切反映了人类的经历。根据市场分析，ProCertus得出结论，放射性皮炎的局部预防剂将受到癌症患者的欢迎，并产生2.5亿美元的年收入。DermX产品将减少放射治疗相关的疼痛，可能使更积极的放射治疗，其中皮炎是剂量限制， 并且可以降低放射治疗疗程后期的脱落率。第二阶段的资金将使我们能够 解决DermX科学发展中的关键和剩余问题，这些问题是：i）确保局部施用的DermX不影响裸鼠中肿瘤细胞异种移植物的外部射束辐射杀伤，ii）优化局部递送载体，其能够实现皮肤干细胞的完全辐射保护，同时允许不显著水平的DermX活性剂进入体循环，和iii）在提交其研究新药（IND）状态之前完成研究所需的DermX的cGMP认证的批量合成。 在该II期项目结束时，ProCertus设想DermX产品可用于临床试验：i）是一种无全身副作用的局部溶液，ii）在放疗前30分钟内应用1-2次，iii）预计可预防放疗患者通常发生的1-4级皮炎。