继GLP-1类药物在糖尿病、减重及心肾疾病领域取得巨大成功后，制药行业正全力押注食欲素（Orexin）这一神经肽，以期掀起脑部疾病治疗的新革命。8月5日，美国监管机构批准了日本武田制药研发的Oveporexton，这是首款用于治疗发作性睡病的食欲素受体激动剂。礼来公司在6月以高达78亿美元的交易收购了生物科技公司Centessa以布局该赛道；摩根士丹利预计，到2035年仅发作性睡病及相关睡眠障碍领域的食欲素药物年销售额就可达160亿美元，远超目前该领域30亿美元的市场规模。食欲素系统涵盖OX1R和OX2R两种受体，不仅调控觉醒状态，还深度参与注意力、动机与奖赏机制，使得全球数以亿计的抑郁症、多动症（ADHD）及成瘾症患者有望从中获益。
发作性睡病1型（NT1）源于下丘脑中产生食欲素的神经元丧失，导致患者出现严重日间嗜睡并伴随情绪触发的猝倒发作。传统的兴奋剂或促醒剂仅能缓解症状且伴随焦虑、高血压和成瘾风险，而OX2R受体激动剂则从上游整体协调去甲肾上腺素、五羟色胺和多巴胺等多条神经通路，产生更稳定且自然的清醒状态。在一项涉及90名患者的为期八周的临床试验中，Oveporexton使NT1患者在清醒维持测试中的清醒时间延长了12.5至25分钟，并将猝倒发作频率降至安慰剂组的大约三分之一。此外，礼来收购的食欲素激动剂在55名患者的试验中，也成功使NT1和NT2患者的清醒时间分别延长了20多分钟和10多分钟。
制药企业目前正将食欲素类药物的研发版图从罕见的睡眠障碍扩展至更为广泛的神经与精神疾病。爱尔兰生物科技公司Alkermes正探索食欲素激动剂在成人多动症中的疗效，其他团队则在评估其治疗睡眠呼吸暂停的潜力。在奖赏回路方面，阻断OX1R受体在抑制成瘾性渴求方面展现出前景，而激活OX1R则可能为改善动机缺失和特定类型的抑郁症提供全新疗法。正如调节饥饿与代谢的GLP-1药物重塑了医学，科学家和药企期待作为机体平衡主控机制之一的食欲素靶向药物，能够成为下一个现象级的脑科学疗法。
Following the transformative clinical and commercial impact of GLP-1 receptor agonists in metabolic disease, the pharmaceutical industry is aggressively pivoting to orexins—neurotransmitters regulating wakefulness, motivation, and reward—to develop groundbreaking treatments for brain disorders. On August 5th, US regulators approved Takeda’s oveporexton as the first-in-class orexin-2 receptor (OX2R) agonist for narcolepsy, a condition affecting approximately one in 2,000 Americans. Capitalizing on this momentum, Eli Lilly acquired Centessa in June for up to $7.8bn to secure early-stage pipeline assets, while Morgan Stanley forecasts annual sales of orexin medicines to hit $16bn by 2035 for sleep disorders alone, compared to $3bn in current market treatments. Beyond sleep medicine, orexin therapeutics hold broader potential for conditions affecting hundreds of millions, including depression, ADHD, and substance addiction.
Narcolepsy type 1 (NT1) is caused by the autoimmune loss of hypothalamus neurons producing orexin, leading to debilitating daytime somnolence and cataplexy—a sudden emotional loss of muscle control. Unlike conventional stimulants that carry risks of hypertension, insomnia, and abuse, OX2R agonists act upstream to harmonize multiple neurotransmitter networks naturally. In an eight-week clinical trial of 90 patients, oveporexton significantly extended daytime wakefulness by 12.5 to 25 minutes during Maintenance of Wakefulness tests and reduced cataplexy attacks to roughly one-third of the frequency seen in the placebo group. Similarly, Lilly's investigational agonist demonstrated encouraging preliminary efficacy in a 55-patient study, extending wakefulness by over 20 minutes in NT1 patients and over 10 minutes in type 2 narcolepsy (NT2).
Pharmaceutical developers are now rapidly extending orexin modulation toward widespread neuropsychiatric conditions. Alkermes is initiating trials for adult ADHD based on enhanced attention observed in narcolepsy patients, while other researchers target obstructive sleep apnea. Concurrently, manipulating the OX1R receptor offers novel neurochemical avenues: antagonist compounds show strong efficacy in curbing addictive cravings, whereas activating OX1R could potentially treat refractory depression and restore motivational circuitry. As master homeostatic regulators alongside metabolic pathways, orexin-targeting therapies are positioned to replicate the multi-indication paradigm of GLP-1s across mainstream neuroscience.
Source: The brain may be about to have its Ozempic moment
Subtitle: Pharma’s newest obsession involves mimicking the system that keeps people awake
Dateline: 8月 13, 2026 05:04 上午