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

开发子宫内膜消融药物装置组合来治疗月经出血

• 批准号: 10759501
• 负责人: Oleg Shikhman
• 金额: $ 30.08万
• 依托单位: GYNION, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-05 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10759501
• 关键词: Ablation; Address; Adoption; Affect; Aftercare; Anesthesia procedures; Animal Model; Animals; Blood Transfusion; Blood specimen; Breast Cancer Risk Factor; Caring; Catheters; Cervical; Chemicals; Clinical; Clinical Research; Complex; Data; Development; Devices; Diameter; Dose; Drug Formulations; Effectiveness; Emotional; Endometrial; Endometrium; Environment; Excision; Extravasation; Family suidae; Formulation; Goals; Gynecologist; Healthcare; Hemorrhage; Histopathology; Hormonal; Hospitalization; Hour; Human; Hysterectomy; Injections; International; Intrauterine Devices; Iron deficiency anemia; Legal patent; Liquid Chromatography; Local Anesthetics; Local anesthesia; Mammalian Oviducts; Marketing; Measures; Medical Device; Menstrual cycle; Methodology; Methods; Modality; Modeling; Operating Rooms; Operative Surgical Procedures; Oral; Organ; Pain; Patients; Perioperative; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Pilot Projects; Plasma; Positioning Attribute; Postoperative Complications; Procedures; Process; Production; Progestins; Qualifying; Quality of life; Risk; Safety; Sales; Services; Small Business Innovation Research Grant; Surface; System; Therapeutic; Time; Tissues; Toxic effect; Toxicology; Trichloroacetic Acid; Uterine cavity; Uterus; Viscosity; Woman; appropriate dose; clinical trial enrollment; commercialization; cost; cost effective; cost effective treatment; cost effectiveness; experimental study; hemodynamics; implantable device; in vivo; innovation; interest; low and middle-income countries; mass spectrometer; novel therapeutics; porcine model; pressure; side effect; social; systemic toxicity

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.

项目摘要 在美国，超过1000万妇女和全球妇女患有大量月经出血（HMB）。 口服药物缺乏效果，并且像荷尔蒙宫内宫内宫内药物（宫内设备）一样，具有显着的副作用。 当前可用的子宫内膜消融选项，这是另一种治疗替代方案，很复杂， 需要高级麻醉，这大大限制了其办公室内使用。由于成本高，复杂性， 和/或可用选择的临床限制，数百万妇女没有接受治疗或被迫 进行子宫切除术。估计对全球HMB进行了2-300万个子宫切除术，包括 〜400,000仅在美国。 Gynion将通过Menorrx（一种药物/设备组合）来满足这种未满足的需求 对HMB进行无创，易于使用且具有成本效益的疗法。它旨在由产科医生使用 妇科医生（OB-GYN）在办公室环境中仅需要局部麻醉。月经 是使用三氯乙酸（TCA）作为活性成分的专有药物制剂。配方是 灌输到子宫腔中，然后用创新的递送对子宫内膜层进行化学烘烤 确保程序安全性和一致结果的系统。这个SBIR项目的长期目标是推销 全球月经，由于其简单，安全性，高效能，使HMB治疗更加可用且负担得起 和成本效益。为了实现这一目标，妇产科需要在美国获得法规批准，并 国际。此类批准要求公司进行动物和人类临床研究 展示产品安全性，包括毒理学安全性和功效。目标1的重点是证明 约克郡猪是一种可行的体内动物模型，用于蒙诺克的宫内滴注。适合物种 将开发剂量的月经，并在96小时的非GLP研究中对三头猪进行治疗。之后 治疗，组织病理学评估将确认剂量安全。 AIM 2是评估初始系统的低 通过宫内滴注并确定毒性峰何时发生的月经的毒性。 在第二阶段，妇产科将使用该猪模型进行72小时和30天的符合GLP的生存研究 评估系统性毒性水平，并确认TCA的长期全身毒性作用。这将允许妇产科 建立初步毒理学安全并启动人类毒性研究，作为监管部门批准的一部分 过程。根据第505（b）（2）条获得妇产科在美国获得新药申请（NDA）批准后 FD＆C Act和CE Mark，它将在全球市场上商业化概念，预计将达到$ 1.6B 与一支小型的美国销售人员和国际分销商一起。一旦商业生存能力和快速采用 已证明，该公司将通过主要的医疗设备或 制药公司。