Development of an endometrial ablation drug-device combination to treat heavy menstrual bleeding

项目总结 美国有1000多万女性，全球有1亿女性患有月经大出血(HMB)。 口服药物缺乏效果，与激素性宫内节育器(宫内节育器)一样，也有明显的副作用。 目前可用的子宫内膜消融术是另一种治疗方法，它很复杂，而且 需要高级麻醉，这大大限制了他们在办公室的使用。因为成本高，复杂， 和/或现有选择的临床局限性，数百万妇女没有接受治疗或被迫 接受子宫切除术。据估计，全世界有200-300万例子宫切除手术，包括 仅在美国就有40万人。Gynion将通过Mnowrx解决这一未得到满足的需求，Mnowrx是一种药物/设备组合，将 是一种非侵入性、易于使用和成本效益高的HMB治疗方法。它是专供产科医生使用的- 妇科医生(OB-GYN)在办公室环境中执业，只需要局部麻醉。美诺瑞克斯 是一种使用三氯乙酸(TCA)作为活性成分的专利药物配方。它的配方是 注入宫腔，然后使用创新的分娩方式化学消融子宫内膜层 确保程序安全和结果一致的系统。这个SBIR项目的长期目标是推向市场 由于其简单、安全、高效、 和成本效益。为了实现这一目标，Gynion需要获得美国监管部门的批准，并 在国际上。此类批准要求该公司进行动物和人体临床研究，以 展示产品安全，包括毒理安全性和有效性。目标1的重点是证明 约克夏猪是宫内注射美诺昔布的活体动物模型。一个适合物种的物种 将开发剂量的Mnowrx，并将在96小时的非GLP研究中治疗三头猪。后 治疗后，组织病理学评估将确认剂量安全。目标2是评估低初始全身性 通过宫内滴注给药的美诺昔布的毒性，并确定毒性峰值出现的时间。 在第二阶段，Gynion将使用这种猪模型进行72小时和30天的符合GLP的生存研究，以 评估全身毒性水平，并确认三氯乙酸没有长期全身毒性影响。这将允许Gynion 作为监管批准的一部分，建立初步毒理学安全性并启动人体毒性研究 进程。在Gynion根据第505(B)(2)条在美国获得新药申请(NDA)批准后 FD&C法案和CE标志，它将使Mnowrx在全球市场商业化，预计全球市场将达到16亿美元 与一支规模较小的美国直销队伍和国际分销商合作。一旦商业可行性和快速采用 证明，该公司将处于有利地位，可以被大型医疗设备或 一家制药公司。

PROJECT SUMMARY Over 10 million women in the US and 100 million women globally suffer from Heavy Menstrual Bleeding (HMB). Oral medications lack effectiveness and, like hormonal IUDs (intrauterine devices), have significant side effects. Currently available endometrial ablation options, which is another therapeutic alternative, are complex and require advanced anesthesia, which significantly limits their in-office use. Because of the high cost, complexity, and/or clinical limitations of the available options, millions of women receive no treatment or are compelled to undergo a hysterectomy. An estimated 2-3 million hysterectomies are done for HMB worldwide, including ~400,000 just in the US. Gynion will address this unmet need with Menorrx, a drug/device combination that will be a non-invasive, easy-to-use, and cost-effective therapy for HMB. It is intended for use by obstetrician- gynecologists (OB-GYN) practitioners in an office setting with the requirement of only local anesthesia. Menorrx is a proprietary drug formulation that uses Trichloroacetic Acid (TCA) as an active ingredient. The formulation is instilled into the uterine cavity which then chemically ablates an endometrial layer using an innovative delivery system that assures procedural safety and consistent results. The long-term goal of this SBIR project is to market Menorrx globally, making HMB treatment more available and affordable due to its simplicity, safety, high efficacy, and cost-effectiveness. To achieve this goal, Gynion needs to obtain regulatory approvals in the US and internationally. Such approvals require the company to conduct animal and human clinical studies to demonstrate product safety, including toxicological safety, and efficacy. The focus of Aim 1 is to demonstrate that the Yorkshire pig is a viable in vivo animal model for intrauterine instillation of Menorrx. A species-appropriate dose of Menorrx will be developed, and three pigs will be treated in the 96-hour non-GLP study. After the treatment, a histopathology assessment will confirm dose safety. Aim 2 is to assess the low initial systemic toxicity of Menorrx that is administered by intrauterine instillation and determine when the peak of toxicity occurs. In Phase II, Gynion will conduct a 72-hour and 30-day GLP-compliant survival study using this pig model to assess systemic toxicity levels and confirm no long-term systemic toxicity effects of TCA. This will allow Gynion to establish preliminary toxicology safety and initiate a human toxicity study as part of the regulatory approval process. After Gynion obtains New Drug Application (NDA) approval in the US under section 505(b)(2) of the FD&C Act, and a CE Mark, it will commercialize Menorrx in the global market that is projected to reach $1.6B with a small direct US sales force and with international distributors. Once commercial viability and rapid adoption are demonstrated, the company will be well-positioned for acquisition by a major medical device or pharmaceutical company.