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.

项目概要 美国有超过 1000 万女性，全球有超过 1 亿女性患有月经过多出血 (HMB)。 口服药物缺乏疗效，并且与激素宫内节育器（宫内节育器）一样，具有显着的副作用。 目前可用的子宫内膜去除术是另一种治疗选择，它很复杂并且 需要高级麻醉，这极大地限制了它们在办公室的使用。由于成本高、结构复杂， 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接受治疗 接受子宫切除术。据估计，HMB 在全球范围内进行了 2-300 万例子宫切除术，其中包括 仅在美国就有约 400,000 人。 Gynion 将通过 Menorrx 解决这一未满足的需求，这是一种药物/设备组合，将 是一种非侵入性、易于使用且具有成本效益的 HMB 治疗方法。它供产科医生使用- 办公室环境中仅需要局部麻醉的妇科医生 (OB-GYN) 从业人员。梅诺克斯 是一种专有药物配方，使用三氯乙酸（TCA）作为活性成分。配方为 注入子宫腔，然后使用创新的输送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。该 SBIR 项目的长期目标是将 Menorrx 在全球范围内，由于其简单、安全、高效，使 HMB 治疗更容易获得和负担得起， 和成本效益。为了实现这一目标，Gynion 需要获得美国和监管机构的批准 国际上。此类批准要求公司进行动物和人体临床研究 证明产品安全性，包括毒理学安全性和功效。目标 1 的重点是展示 约克夏猪是用于宫内滴注 Menorrx 的可行体内动物模型。适合物种的 将开发 Menorrx 的剂量，并在 96 小时非 GLP 研究中对三头猪进行治疗。之后 治疗后，组织病理学评估将确认剂量安全性。目标 2 是评估低初始系统性 通过宫内滴注给药的 Menorrx 的毒性并确定何时出现毒性峰值。 在第二阶段，Gynion 将使用该猪模型进行 72 小时和 30 天的 GLP 合规生存研究 评估全身毒性水平并确认 TCA 没有长期全身毒性作用。这将使吉尼翁 作为监管批准的一部分，建立初步的毒理学安全性并启动人体毒性研究 过程。 Gynion 根据 FDA 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，它将在预计达到 $1.6B 的全球市场上将 Menorrx 商业化 在美国拥有小型直接销售队伍和国际分销商。一旦商业可行性和快速采用 事实证明，该公司将处于有利地位，可以被主要医疗设备或 制药公司。