Naltrexone Hydrochloride

来源 | 医脉通内分泌科 肥胖是一种多因素导致的慢性疾病，其特征是身体脂肪的功能失调性或过度性积累。这种疾病不仅影响个体器官的功能，还会对整个身体系统产生负面影响，从而引发一系列并发症。这些并发症可以分为两大类： 一类是由于脂肪质量增加导致的机械力改变而引发的“脂肪质量病（FAT MASS DISEASES）”，如睡眠呼吸暂停综合征（OSAS）和膝关节骨关节炎（KOA）； 另一类则是与代谢、内分泌、炎症和免疫反应失调相关的“病态脂肪疾病（SICK FAT DISEASES）”，如2型糖尿病（T2DM）、心血管疾病（CVD）和代谢功能障碍相关脂肪肝疾病（MASLD）等。 2025年10月2日，《欧洲肥胖研究协会 (EASO) 关于肥胖及其并发症药理治疗的框架》于nature medicine重磅发布，为肥胖及其并发症的临床治疗提供了全新的视角。 图 EASO针对肥胖个体的治疗建议 肥胖管理：从单一减重到全面健康改善 传统的肥胖管理主要集中在体重减轻上，但EASO的新框架强调，肥胖管理应采用更全面的方法，不仅要减轻体重，还要预防、解决或改善并发症，提升心理健康、身体素质、社交功能以及整体健康和生活质量。行为改变（包括治疗性营养、治疗性体育活动、压力管理和睡眠改善）是肥胖管理的基础，同时可能需要结合心理支持、肥胖管理药物以及代谢或减重手术（外科和内镜手术）。 近年来，可用于治疗肥胖的药物数量稳步增加，为临床医生提供了更多选择。不同的药物在减轻体重和对肥胖相关并发症的影响方面存在差异，因此，基于个体患者特征的个体化治疗变得可行且必要。EASO提出的治疗策略旨在帮助临床医生根据每位患者的健康背景选择合适的药物。 药物治疗：选择与考量 01 没有并发症的个体：减重为主要目标 在没有并发症的个体中，减轻体重仍然是治疗的主要目标，以降低发生并发症的风险。所有获得批准的药物与安慰剂相比都能显著减轻体重，但不同药物在减轻体重方面的效果存在差异。例如，替尔泊肽和司美格鲁肽在与安慰剂相比时，体重减轻超过10%，而奥利司他、naltrexone–bupropion、利拉鲁肽和phentermine–topiramate的效果则较小。 在选择药物时，应考虑药物对体重减轻的效果、对并发症的影响以及安全性。根据临床试验结果，替尔泊肽和司美格鲁肽在需要显著减轻体重时应作为首选药物。而对于需要适度减轻体重的个体，可以选择范围更广的药物。 02 已存在并发症的个体：精准治疗 对于已经存在并发症的个体，选择最合适的药物应基于药物对并发症改善或缓解的证据。药物对肥胖相关并发症的影响是异质性的，并不总是与体重减轻的程度成正比，这可能反映了药物除了减轻体重之外的直接药理作用。因此，EASO的治疗策略是基于药物对特定并发症的影响的科学证据合成而开发的。 ➤睡眠呼吸暂停综合征（OSAS）：目前，只有替尔泊肽在针对肥胖个体的OSAS影响的随机对照试验中显示出更高的OSAS缓解率，并显著降低了呼吸暂停-低通气指数。因此，替尔泊肽应被视为肥胖和OSAS患者的一线治疗药物。 ➤膝关节骨关节炎（KOA）：在针对肥胖和膝关节骨关节炎个体的两项随机对照试验中，分别研究了利拉鲁肽和司美格鲁肽。研究表明，司美格鲁肽比利拉鲁肽更能减轻疼痛。因此，司美格鲁肽应被视为肥胖和膝关节骨关节炎患者的一线治疗药物。 ➤糖尿病前期和2型糖尿病：在针对糖尿病前期和糖尿病患者的试验中，替尔泊肽、司美格鲁肽、利拉鲁肽以等都能显著改善血糖参数，并在不同程度上实现2型糖尿病的缓解。替尔泊肽、司美格鲁肽和利拉鲁肽还降低了超重/肥胖和糖尿病前期个体进展为2型糖尿病的发病率。因此，替尔泊肽和司美格鲁肽应作为肥胖和血糖异常个体的首选药物。 ➤心血管疾病：在针对心血管结局的随机对照试验中，司美格鲁肽显示出显著降低有心血管事件史个体的主要不良心血管事件（MACE）发病率的效果，而naltrexone–bupropion则未显示出显著的心血管益处。因此，司美格鲁肽应推荐给有心血管病史的个体。 ➤心力衰竭：在针对心力衰竭患者的试验中，司美格鲁肽和替尔泊肽均显示出降低心力衰竭住院风险的效果，无论患者是射血分数保留型还是射血分数降低型心力衰竭。尽管如此，目前的数据仍不足以对这两种药物分别在不同情况下的使用提出具体建议。目前，替尔泊肽和司美格鲁肽应被视为肥胖和心力衰竭患者的一线治疗药物。 ➤代谢功能障碍相关脂肪性肝病（MASLD）：在针对MASLD患者的试验中，只有替尔泊肽显示出对代谢功能障碍相关脂肪性肝炎（MASH）的缓解和肝纤维化改善的效果。目前推荐使用替尔泊肽治疗肥胖合并MASLD患者。值得注意的是，未纳入本指南的3期ESSENCE试验（因该试验于2025年1月31日后发表）显示，司美格鲁肽与替尔泊肽类似，与MASH和肝纤维化的显著改善相关。 未来展望：个体化治疗与新发现 尽管大多数药物尚未针对特定并发症进行专门评估，但随着对肥胖作为脂肪质量疾病和病态脂肪疾病的理解不断发展，药物治疗的潜力也在不断增长。未来，药物有望对更广泛的并发症产生积极影响，包括慢性肾脏病、神经退行性疾病、多囊卵巢综合征、某些癌症和心理健康状况等。 EASO提出的药物使用框架强调了根据个体情况量身定制治疗方案的重要性。这一框架基于当前的科学证据，通过系统回顾和网络荟萃分析已发表的临床试验而开发。这种方法与将肥胖视为一种基于脂肪的慢性疾病的概念一致，区分了与脂肪质量相关的主要因素和与功能失调（或“病态”）脂肪相关联的因素。 为个体量身定制治疗方案是一项复杂的任务，需要考虑多个因素，包括脂肪质量的严重程度、并发症的存在和程度、合并症和同时进行的治疗。社会经济背景、患者的价值观、期望和个人目标也必须被考虑在内。尽管没有任何治疗策略可以取代这种全面评估所需的细致临床判断，但这一工具可以为肥胖治疗的决策提供支持。鉴于药物领域的快速发展，EASO计划定期更新当前的治疗策略，以纳入最新的可用证据。 总之，EASO的最新框架为肥胖及其并发症的药理治疗提供了全面、科学的指导，强调了个体化治疗的重要性，并为临床医生在肥胖治疗中的决策提供了有力的支持。 参考文献 McGowan, B., Ciudin, A., Baker, J.L. et al. Framework for the pharmacological treatment of obesity and its complications from the European Association for the Study of Obesity (EASO). Nat Med (2025). https://doi.org/10.1038/s41591-025-03765-w 责编｜Zelda 封面图来源｜视觉中国 超57%医务人员收入下降，集体降薪时代，不同医院不同医生的收入差距 刚刚！2025年诺贝尔生理学或医学奖重磅揭晓！ 医脉通是专业的在线医生平台，“感知世界医学脉搏，助力中国临床决策”是平台的使命。医脉通旗下拥有「临床指南」「用药参考」「医学文献王」「医知源」「e研通」「e脉播」等系列产品，全面满足医学工作者临床决策、获取新知及提升科研效率等方面的需求。 ☟戳这里，更有料！

PALO ALTO, Calif., Oct. 01, 2025 (GLOBE NEWSWIRE) -- Scilex Holding Company (“Scilex” or the “Company”) (Nasdaq: SCLX), an innovative revenue-generating company focused on acquiring, developing and commercializing non-opioid pain management products for the treatment of acute and chronic pain and neurodegenerative and cardiometabolic disease, today announced that it has repurchased 3,130,000 warrants to purchase shares of Scilex common stock having an exercise price of $0.01 per share (“Warrants”) from Oramed Pharmaceuticals Inc. (“Oramed”) for $13,000,000. As previously disclosed, Scilex entered into an option agreement with Oramed for the repurchase of Warrants, pursuant to which, among other things, Oramed granted an option to Scilex to repurchase 6,500,000 warrants in two tranches for an aggregate purchase price of $27,000,000. Scilex continues to have the option to repurchase the remaining 3,370,000 warrants from Oramed for $14,000,000 on or before December 31, 2025. For more information on Scilex Holding Company, refer to www.scilexholding.com For more information on Semnur Pharmaceuticals, Inc., refer to www.semnurpharma.com For more information on ZTlido® including Full Prescribing Information, refer to www.ztlido.com For more information on ELYXYB®, including Full Prescribing Information, refer to www.elyxyb.com For more information on Gloperba®, including Full Prescribing Information, refer to www.gloperba.com https://www.facebook.com/scilex.pharm https://www.linkedin.com/company/scilex-holding-company/ info@scilexholding.com About Scilex Holding Company Scilex is an innovative revenue-generating company focused on acquiring, developing and commercializing non-opioid pain management products for the treatment of acute and chronic pain and neurodegenerative and cardiometabolic disease. Scilex targets indications with high unmet needs and large market opportunities with non-opioid therapies for the treatment of patients with acute and chronic pain and is dedicated to advancing and improving patient outcomes. Scilex’s commercial products include: (i) ZTlido® (lidocaine topical system) 1.8%, a prescription lidocaine topical product approved by the U.S. Food and Drug Administration (the “FDA”) for the relief of neuropathic pain associated with postherpetic neuralgia, which is a form of post-shingles nerve pain; (ii) ELYXYB®, a potential first-line treatment and the only FDA-approved, ready-to-use oral solution for the acute treatment of migraine, with or without aura, in adults; and (iii) Gloperba®, the first and only liquid oral version of the anti-gout medicine colchicine indicated for the prophylaxis of painful gout flares in adults. In addition, Scilex has three product candidates: (i) SP-102 (10 mg, dexamethasone sodium phosphate viscous gel) (“SEMDEXA” or “SP-102”), which is owned by Semnur (a majority owned subsidiary of Scilex) and is a novel, viscous gel formulation of a widely used corticosteroid for epidural injections to treat lumbosacral radicular pain, or sciatica, for which Scilex has completed a Phase 3 study and was granted Fast Track status from the FDA in 2017; (ii) SP-103 (lidocaine topical system) 5.4%, (“SP-103”), a next-generation, triple-strength formulation of ZTlido, for the treatment of acute pain and for which Scilex has recently completed a Phase 2 trial in acute low back pain. SP-103 has been granted Fast Track status from the FDA in low back pain; and (iii) SP-104 (4.5 mg, low-dose naltrexone hydrochloride delayed-release capsules) (“SP-104”), a novel low-dose delayed-release naltrexone hydrochloride being developed for the treatment of fibromyalgia. Scilex is headquartered in Palo Alto, California. Forward-Looking Statements This press release includes forward-looking statements that involve risks and uncertainties. Forward-looking statements are statements that are not historical facts and may be accompanied by words that convey projected future events or outcomes, such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook” or variations of such words or by expressions of similar meaning. These forward-looking statements include, but are not limited to, statements regarding future events, repurchase of warrants, future opportunities for Scilex and its subsidiaries, the future business strategies, long-term objectives and commercialization plans of Scilex and its subsidiaries, the current and prospective product candidates, planned clinical trials and preclinical activities and potential product approvals, as well as the potential for market acceptance of any approved products and the related market opportunity of Scilex and its subsidiaries, statements regarding SP-102, if approved by the FDA, Scilex’s potential to attract new capital and avoid the effects of negative debt leverage and other statements that are not historical facts. These statements are based on management’s current expectations of and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on, by any investor as a guarantee, an assurance, a prediction or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and will differ from assumptions. Many actual events and circumstances are beyond the control of Scilex. These statements are subject to a number of risks and uncertainties regarding Scilex’s business, and actual results may differ materially. These risks and uncertainties include, but are not limited to, general economic, political and business conditions; the ability of Scilex and its subsidiaries to develop and successfully market products; the ability of Scilex and its subsidiaries to grow and manage growth profitably and retain its key employees; the risk that the potential product candidates that Scilex develops may not progress through clinical development or receive required regulatory approvals within expected timelines or at all; risks relating to uncertainty regarding the regulatory pathway for Scilex’s product candidates; the risk that Scilex’s product candidates may not be beneficial to patients or successfully commercialized; the risk that Scilex has overestimated the size of the target patient population, their willingness to try new therapies and the willingness of physicians to prescribe these therapies; risks that the prior results of the clinical trials may not be replicated; regulatory and intellectual property risks; the risk of failure to realize the anticipated benefits of the previously announced transactions with Datavault AI Inc., and other risks and uncertainties indicated from time to time and other risks set forth in Scilex’s filings with the SEC. There may be additional risks that Scilex presently does not know or that Scilex currently believes are immaterial that could also cause actual results to differ from those contained in the forward-looking statements. In addition, forward-looking statements provide Scilex’s expectations, plans or forecasts of future events and views as of the date of the communication. Scilex anticipates that subsequent events and developments will cause such assessments to change. However, while Scilex may elect to update these forward-looking statements at some point in the future, Scilex specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Scilex’s assessments as of any date subsequent to the date of this communication. Accordingly, investors are cautioned not to place undue reliance on these forward-looking statements. Contacts: Investors and MediaScilex Holding Company 960 San Antonio RoadPalo Alto, CA 94303Office: (650) 516-4310 Email: investorrelations@scilexholding.com Website: www.scilexholding.com SEMDEXA™ (SP-102) is a trademark owned by Semnur Pharmaceuticals, Inc., a majority-owned subsidiary of Scilex Holding Company. A proprietary name review by the FDA is planned. ZTlido® is a registered trademark owned by Scilex Pharmaceuticals Inc., a wholly-owned subsidiary of Scilex Holding Company. Gloperba® is the subject of an exclusive, transferable license to use the registered trademark by Scilex Holding Company. ELYXYB® is a registered trademark owned by Scilex Holding Company. Scilex Bio™ is a trademark owned by Scilex Holding Company, Inc. All other trademarks are the property of their respective owners. © 2025 Scilex Holding Company All Rights Reserved.