Nalmefene Implant for the Long-Term Treatment of Opioid Use Disorder

项目总结： 纳美芬植入剂长期治疗阿片类药物使用障碍 美国目前面临着一场重大危机，原因是阿片类药物过量导致的死亡人数不断增加 美国人患有一种名为阿片类药物使用障碍(OUD)的慢性疾病。阿片类药物的危害 滥用和上瘾也会带来巨大的经济代价。使用阿片类激动剂治疗OUD， 或在用阿片类拮抗剂戒毒后，是安全有效的，可以减少或消除 戒断症状，钝化或阻止非法阿片类药物的影响，并减少或消除渴望。然而，一个 处于缓解期的受试者有很高的机会再次使用阿片类药物；这种情况可能在任何时候发生--从几个月开始 戒毒后几天到几个月。阿片类拮抗剂预防治疗可阻断阿片类药物的作用 阿片类药物的使用，是预防戒毒后复发的有效治疗方法，具有潜在的应用价值 过量死亡；然而，患者对维持脑内阿片类药物所必需的频繁剂量的依从性较低 受体的阻断阻止了广泛的采用。对慢性治疗的迫切需求尚未得到满足 能够在6个月或更长时间内提供增强的合规性，以防止OUD复发和 戒毒受试者的再矿化。泰坦的专利皮下植入物可以提供长期的、非 在基于办公室的单一插入程序之后，持续波动的药物治疗水平。非-- 可生物降解的固体基质植入物配方几乎消除了意外药物倾倒的风险和 相关的严重毒性，其皮下位置确保了患者对6个月治疗的依从性 持续时间。盐酸纳美芬(纳美芬)是一种阿片受体拮抗剂 以及逆转阿片类药物过量，包括呼吸抑制。其相对于其他阿片类拮抗剂的优势 包括更高的效力，更长的半衰期，并且没有肝脏毒性。植入原型纳美芬植入物 大鼠皮下连续服用纳美芬数月，未发现任何可观察到的安全性问题。这个 数据表明，三分之一的植入物可能提供足够的药物来提供高达90%的阻断 人脑阿片受体。由于纳美芬是FDA批准的药物，而且因为泰坦的植入物 技术已经在用于OUD的维护治疗的批准和销售的产品中得到验证， 开发这一产品的潜在监管风险相对较低。开发可能具有成本效益 而这种预防复发的产品成功商业化的可能性很高 阿片类药物依赖，阿片类药物戒毒后。目标是开发一种可植入6个月的装置 它以稳定的速度全天候提供纳美芬，以防止阿片类药物依赖的复发 阿片类药物戒毒。目标是制造纳美芬植入物，完全非临床安全性和 药理学研究，并在OUD对象中进行临床研究以支持新药申请。这 新产品可能会潜在地改善治疗的有效性，增强依从性，降低个体 和社会成本，并大大有助于减轻这一流行病的致命后果。

Project Summary: Nalmefene Implant for the Long-Term Treatment of Opioid Use Disorder The U.S. currently faces a major crisis from the increasing number of deaths due to opioid overdose among Americans afflicted with the chronic medical condition called opioid use disorder (OUD). Harm from opioid misuse and addiction also comes at a huge economic cost. Pharmacotherapy for OUD with an opioid agonist, or following detoxification with an opioid antagonist, is safe and effective, and can reduce or eliminate withdrawal symptoms, blunt or block the effects of illicit opioids, and reduce or eliminate cravings. However, an OUD subject in remission has a high chance of relapse to opioid use; which can occur at any time - from a few days to months following detoxification. Prophylactic treatment with opioid antagonists can block the effect of opioid use and can be an effective treatment for preventing OUD relapse following detoxification and potential overdose death; however, low patient compliance to frequent dosing necessary to maintain brain opioid receptor blockade has prevented widespread adoption. There is an urgent unmet need for a chronic treatment paradigm capable of providing enhanced compliance for 6-months or longer to prevent OUD relapse and renarcotization in detoxified subjects. Titan's proprietary subdermal implants can provide long-term, non- fluctuating therapeutic levels of drug continuously following a single office-based insertion procedure. The non- biodegradable solid matrix implant formulation virtually eliminates the risk of accidental drug dumping and associated serious toxicity, and its subdermal location assures patient compliance for the 6-month treatment duration. Nalmefene hydrochloride (nalmefene) is an opioid receptor antagonist approved for the management and reversal of opioid overdose, including respiratory depression. Its advantage over other opioid antagonists includes higher potency, longer half-life, and no liver toxicity. Prototype nalmefene implants inserted subdermally in rats delivered nalmefene continuously for months without any observable safety concerns. The data suggests that one-three implants could potentially deliver sufficient drug to provide up to 90% blockage of human brain opioid receptors. Since nalmefene is an FDA approved drug, and because Titan's implant technology has been validated in an approved and marketed product for the maintenance treatment of OUD, the potential regulatory risk for developing this product is relatively low. Development could be cost-effective and the probability is high for successful commercialization of this product for the prevention of relapse to opioid dependence, following opioid detoxification. The objective is to develop a 6-month implantable device that delivers nalmefene around the clock at a steady rate to prevent relapse to opioid dependence following opioid detoxification. The goals are to manufacture nalmefene implants, complete nonclinical safety and pharmacology studies, and conduct clinical studies in OUD subjects to support a New Drug Application. This novel product could potentially improve effectiveness of the treatment, enhance compliance, lower individual and societal costs, and significantly contribute towards alleviating the deadly consequences of this epidemic.