To assess the long-term safety and tolerability of XEN496 in pediatric subjects with KCNQ2 developmental and epileptic encephalopathy (KCNQ2-DEE) who had participated in the primary study (XPF-009-301).

开始日期2021-08-17

申办/合作机构

Xenon Pharmaceuticals, Inc.

NCT04639310

/ Terminated临床3期

A Phase 3 Study of Adjunctive XEN496 in Pediatric Subjects With KCNQ2 Developmental and Epileptic Encephalopathy

To investigate the potential antiseizure effects of adjunctive XEN496 (ezogabine) compared with placebo in children with KCNQ2 Developmental and Epileptic Encephalopathy (KCNQ2-DEE).

开始日期2021-03-29

申办/合作机构

Xenon Pharmaceuticals, Inc.

CTR20182420

/ Completed临床1期

瑞替加滨片单次给药在健康受试者体内的药代动力学预试验

主要研究目的：本研究以天津红日药业股份有限公司生产的瑞替加滨片（50mg）为受试制剂，评估其在空腹条件下给药后的药代动力学初步特征。

开始日期2018-12-17

申办/合作机构

天津红日药业股份有限公司

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100 项与瑞替加滨相关的临床结果

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100 项与瑞替加滨相关的转化医学

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100 项与瑞替加滨相关的专利（医药）

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项与瑞替加滨相关的文献（医药）

2025-11-01·NEUROBIOLOGY OF DISEASE

Human iPSC-derived glutamatergic neurons with pathogenic KCNQ2 variants display hyperactive bursting phenotypes

Article

作者: Scherer, Stephen W ; Yu, Lucy ; Han, Sang Yeon ; Poduri, Annapurna ; Shum, Carole ; Chen, Cidi ; Buttermore, Elizabeth D ; Sundberg, Maria ; Makhortova, Nina R ; Wightman, Emma V ; Kim, Kristina ; Howe, Jennifer ; Norabuena, Erika M ; Sahin, Mustafa

Pathogenic variants in the KCNQ2 gene, which encodes a potassium channel subunit, are associated with neonatal seizures, epileptic encephalopathy, intellectual disability, and autism. Although the consequences of disrupted KCNQ2 channel function have been studied in the past, the detailed molecular mechanisms underlying the development of neurological phenotypes remain unclear, and neuronal models of specific patient variants are lacking. We generated patient-specific induced pluripotent stem cells (iPSCs) from fibroblasts from three individuals with distinct KCNQ2 pathogenic variants. We corrected the KCNQ2 variants using CRISPR-Cas9 editing to create isogenic controls and differentiated these iPSCs into glutamatergic neurons to study the effects of each variant on neuronal function. The three KCNQ2 variants were: 1) KCNQ2 c.875_877delTCCinsCCT, L292_L293delinsPF, 2) KCNQ2 c.766G > T, G256W, and 3) KCNQ2 c.821C > T, T274M. Our data revealed longer neurite outgrowth in two patient lines (T274M and G256W). Transcriptional profiling showed that all three KCNQ2 lines co-expressed genes enriched in synaptic transmission/signaling, cell adhesion, and GTPase signal transduction. Functional analyses of neuronal networks revealed increased burst duration in all three KCNQ2 lines compared with their isogenic controls. Furthermore, neurons from the L292_L293delinsPF and T274M lines displayed increased network connectivity associated with increased density of synaptic markers. Finally, we detected hyperexcitable neuronal networks in the G256W line with electrical stimulation of the neural networks on a high-density microelectrode array, and this phenotype was rescued with retigabine. These disease-related phenotypes for each of the KCNQ2 pathogenic variants can be used for drug screening to identify treatment options for the patients.

2025-11-01·British Journal of Pharmacology

The fast‐dissociating D₂ antagonist antipsychotic JNJ‐37822681 is a neuronal Kv7 channel opener: Potential repurposing for epilepsy treatment

Article

作者: Taglialatela, Maurizio ; Zaliani, Andrea ; Kaji, Marcus ; Barrese, Vincenzo ; Reinshagen, Jeanette ; Carotenuto, Lidia ; Ostacolo, Carmine ; Citraro, Rita ; Gribbon, Philip ; Guida, Natascia ; Weckhuysen, Sarah ; De Sarro, Giovambattista ; Leo, Antonio ; Keminer, Oliver ; Miceli, Francesco ; Dirkx, Nina ; Carleo, Giusy

Abstract:

Background and Purpose:

Pharmacological activation of neuronal M‐current mediated by Kv7 (Kv7.2–5) potassium channels is a validated mechanism for epilepsy treatment. However, since the market withdrawal of the prototype Kv7 activator retigabine, no Kv7 activator is clinically available for this condition. The object was to identify, characterise and validate new neuronal Kv7 channel activators for epilepsy treatment.

Experimental Approach:

A fluorescence‐based high‐throughput assay was optimised in cells stably expressing Kv7 channels to screen two repurposing libraries including >8000 compounds. Whole‐cell patch clamp, in silico docking, mutagenesis and multielectrode array recordings in human induced‐pluripotent stem cell (hiPSCs)‐derived cortical‐like glutamatergic neurons (iNeurons) were used to evaluate compound(s) potency and efficacy, binding site, and effects on neuronal activity, respectively. Finally, anticonvulsant activity was assessed in two acute seizure models in male mice.

Key Results:

JNJ‐37822681, a fast‐dissociating D2 receptor antagonist in clinical development as antipsychotic, enhanced Kv7.2–5 currents with potency and efficacy largely comparable to retigabine. In Kv7.2 subunits, JNJ‐37822681 binding site largely overlapped that for retigabine. In iNeurons, JNJ‐37822681 enhanced the M‐current, hyperpolarised the resting membrane potential and reduced spontaneous action potential firing. These effects were blocked by the Kv7 antagonist, XE‐991, and were not reproduced by the D2 antagonist (‐)‐sulpiride. Finally, JNJ‐37822681 showed anticonvulsant activity in two well‐validated mouse models of acute seizures.

Conclusions and Implications:

Our study reveals that JNJ‐37822681, which lacks retigabine's potential safety issues due to chemical liability and is already confirmed as safe for human use, represents a potential treatment of Kv7‐related neuronal hyperexcitability disorders.

2025-10-01·NEUROBIOLOGY OF DISEASE

Persistent Na+ and M-type K+ currents opposingly control spike gain in CA3 pyramidal cells

Article

作者: Tamir, Idit ; Yaari, Yoel

Neural firing response gain and spike threshold are critical intrinsic cell properties that define input-output relations in neurons. Alterations of these cellular properties in hippocampal pyramidal cells (PCs) may strongly influence network dynamics in health and disease. Here we investigated how specific voltage-gated conductance affect these properties in adult rat CA3 pyramidal cells (PCs) in hippocampal slices under near-physiological conditions. We examined currents activated at near-threshold potential - persistent sodium current (I_NAP), T-type Ca²⁺ current (I_CaT), M-type K⁺ current (I_M), SK Ca²⁺ - dependent current (I_SK)_, and h-type cationic current (I_h) through pharmacological modulation and analysis of resulting changes. CA3 PCs showed high heterogeneity in firing response gain, likely reflecting individual variations in active conductance at rest. Blocking I_NAP by riluzole decreased firing response gain, an effect associated with a reduction in the depolarizing shift (DS) underlying evoked spike trains. Conversely, blocking I_M with XE991 markedly increased firing response gain, decreased the DS, increased input resistance, and lowered spike threshold. Enhancing I_M by retigabine produced opposite effects. Blocking I_SK with apamin moderately augmented firing response gain, while blocking I_CaT and I_h exerted no effect on discharge. Our findings identify I_NaP and I_M as key determinants of spike response gain and threshold of CA3 PCs, suggesting that modulators of these currents may effectively modify neuronal input-output relations in both normal and pathological states of hippocampal hypo- or hyperexcitability.

项与瑞替加滨相关的新闻（医药）

2025-10-31

·PRNewswire

Zhimeng Biopharma's investigational drug CB03-154 for amyotrophic lateral sclerosis has achieved the first patient first dose milestone in the phase 2/3 pivotal clinical trial.

SHANGHAI, Oct. 31, 2025 /PRNewswire/ -- Shanghai Zhimeng Biopharma Inc. ( "Zhimeng") announced that its self-developed new-generation potassium channel opener CB03-154 for the treatment of amyotrophic lateral sclerosis (ALS) has officially initiated the phase 2/3 clinical trial and completed the first patient first dose at the 2nd Affiliated Hospital of Hebei Medical University. Previously (in July 2025), CB03-154 received approval from the China Center for Drug Evaluation (CDE) to conduct the ALS phase 2/3 adaptive clinical trial. The CB03-154 has also been granted orphan drug status in the United States in October 2023 for the treatment of ALS. This phase 2/3 clinical trial is a multicenter, randomized, double-blind, placebo-controlled study with open-label extension. This study is led by Professor Fan Dongsheng from the 3rd Affiliated Hospital of Peking University as the leading investigator nationwide. This study will enroll approximately 240 patients diagnosed with ALS in about 15 centers in China. The disease duration of to be enrolled patients will be within 24 months from the first symptom onset to the screening visit. The primary efficacy endpoint of the study is the change from baseline at week 39 of the revised ALS Functional Rating Scale (ALSFRS-R) score. Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal central nervous system disease with unknown etiology. It mainly affects the motor neurons in the cerebral cortex, brainstem, and spinal cord. The pathological features of ALS include the loss of upper and lower motor neuron cell bodies, as well as the degeneration of the corticospinal tract/corticobulbar tract and axons of lower motor neurons, and the occurrence of denervation changes in muscles. Clinically, it mainly presents as progressive skeletal muscle weakness, atrophy, fasciculation, bulbar palsy, and pyramidal tract signs. The median survival duration is generally 2 to 3 years after the onset of symptoms. The main cause of death is neuromuscular respiratory failure. The annual incidence of ALS in Europe and the United States is 2/100,000 to 3/100,000, and the prevalence rate is 3-5/100,000. The peak age of onset is 50 to 75 years. Approximately 10% of ALS patients are familial, while the remaining 90% are sporadic. Currently, there are no treatments that can stop or reverse the progression of the disease. Therefore, clinical management focuses on early diagnosis and early treatment to maximize the survival time. Currently, only three drugs have been approved worldwide for ALS, namely Riluzole, Edaravone, and Tofersen (trade name Qalsody). These approved drugs can only slightly improve the patient's function or slightly prolong the survival time. Therefore, ALS still has a huge unmet medical need. Although the pathogenesis of ALS has not been fully deciphered, studies have found that it is closely related to changes in ion channels, synaptic transmission and connections, as well as the imbalance of excitation and inhibition of neurons. Among them, the potassium ion (K+) channel is the most widely distributed and has the largest variety, mainly participating in regulating the excitability of neurons and the frequency and amplitude of action potential generation. Currently, there are no marketed KCNQ2/3 potassium ion channel openers available for ALS patients. The only KCNQ2/3 potassium ion channel opener that was approved by the FDA and EMA, ritigabine (Potiga, Ezogabine/Retigabine), was once studied in ALS patients and showed a favorable signal. However, due to the risks of pigmentation-induced vision impairment and other risk factors, it was withdrawn from the market in 2017. CB03-154 is a new generation selective voltage-gated potassium channel (KCNQ2/3) opener, independently developed by Zhimeng. Compared with the first-generation potassium channel opener ritigabine, CB03-154 has superior selectivity and stability. In vitro studies have confirmed that CB03-154 can significantly reduce the excessive excitation of iPSC motor neurons from ALS patients. Moreover, in the SOD-1 ALS transgenic mouse model, daily oral administration of CB03-154 (10 mg/kg) can effectively prolong the survival time, delay the onset, improve motor ability, alleviate neuronal damage, and slow down the rate of muscle atrophy. The initiation of this Phase 2/3 clinical trial is a significant step for CB03-154 in the field of rare diseases, and it brought hopes to provide an important new treatment option for ALS patients. About Zhimeng Founded in 2018, Shanghai Zhimeng Biopharma, Inc. is a biopharmaceutical company dedicated to develop small-molecule drug discovery with focused on the functional cure of chronic hepatitis B (CHB), as well as novel therapies for CNS disorders, including epilepsy, neuropathic pain (e.g. cancer-related pain), amyotrophic lateral sclerosis (ALS), major depressive disorder (MDD), and bipolar disorder. Disclaimer This press release contains forward-looking statements. While Zhimeng considers the projections to be based on reasonable assumptions, these forward-looking statements may be called into question by a number of hazards and uncertainties, so that actual results may differ materially from those anticipated in such forward-looking statements. For more information, please visit: SOURCE Shanghai Zhimeng Biopharma Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

孤儿药上市批准临床研究

2025-09-08

·士研生命科学

八月生物医药风云录：减肥神药、癫痫密码与呼吸新生的突破与沉思

在生物医药这个充满奇迹与挫折的舞台上，每一个月都有无数故事在上演。有的药物一夜成名，有的默默退场，有的在争议中寻找平衡点。作为这个行业的深度观察者，我们见证了太多"山重水复疑无路，柳暗花明又一村"的转折时刻。正是这些起起伏伏的故事，构成了生物医药发展的真实图景，也启发着我们对创新本质的深度思考。八月，恰逢全球生物医药领域迎来了一轮创新成果的密集绽放，从备受争议的减肥新药到精准医学的神经系统突破，再到呼吸疾病治疗的历史性里程碑，每一个案例都值得我们细细品味。让我们以专业的视角和冷静的思辨，解读这场创新与挑战并存的医药风云。减肥神药的双刃剑：VK2735的惊喜与焦虑在这个全民减肥的时代，一款名为VK2735的新药正在掀起波澜。这个来自Viking Therapeutics的"双重武器"——同时激活GLP-1和GIP两个受体的口服减肥药，刚刚在二期临床试验中交出了一份令人瞠目的成绩单。仅仅13周，患者平均减重12%。这是什么概念？一个70公斤的人能减掉8.4公斤，效果堪比胃切除手术。更令人咋舌的是，相比于吃"糖豆"的对照组，VK2735的减重效果足足多出11个百分点。然而，天下没有免费的午餐。就在市场为这一"减肥神药"欢呼雀跃时，一个令人不安的数字悄然浮现：20%的患者因为副作用而中途弃药，高于对照组的13%。同时，在高剂量组，超过三分之一的勇敢尝试者败给了恶心、呕吐等胃肠道反应，早早举起了白旗。从数据上看，VK2735的停药率确实与剂量正相关：在120mg组，提前停药比例高达38%。但同时也要注意到，对照组的提前停药率达到18%，退出研究的比例更是与低剂量组相当（10% vs 13%）。这种“对照组退出率偏高”现象在肥胖药物临床试验中并不罕见，既可能与安慰剂/反安慰剂效应相关，也可能反映出现实中患者对GLP-1热潮下可及疗法的主动选择倾向。因此，单纯将停药率解读为药物耐受性不足，未免失之片面，更应结合分子设计优势与口服递送策略来综合评估其价值。从相关文献来看，体重管理随机对照试验的安慰剂臂本身就存在不容忽视的安慰剂与反安慰剂效应，包括一定比例的体重下降与不良事件报告，这在系统综述/荟萃分析中已有量化，可能间接抬升对照组的退出率。另有大样本研究显示GLP-1在真实世界存在较高的停用与再启用，进一步说明患者行为变量值得纳入试验解读框架。表1 VK2735 临床试验常见不良事件（GI 相关）及停药率数据来源：Viking官网IR资料（点击查看大图）除此之外VK2735在其分子设计在实现“口服减肥药”概念方面有着独特价值。传统肽类药物由于易被胃蛋白酶降解，难以口服给药。Viking采用了磷酸酯前药设计，在脂肪酸侧链末端引入磷酸基团，增加极性和水溶性，有助于药物穿越胃肠屏障。这种“先伪装、再释放”的策略让原本脆弱的肽类在胃内保持稳定，随后在血液中由体内磷酸酶解聚，释放出活性药物。药物辅料SNAC作为渗透促进剂，还能提高胃内局部pH并增强膜流动性，从而促进药物在胃中直接吸收研究表明，基于SNAC的口服肽类药物的吸收确实发生在胃部而非小肠。 VK2735在口服制剂上的这些创新，为未来开发更安全有效的口服肽类药物提供了重要经验。前药策略突破口服难关：磷酸酯前药的精妙设计 VK2735能够实现口服给药的秘密，藏在一个巧妙的分子设计中。Viking公司借鉴了礼来等公司的成功经验，采用了磷酸酯前药策略——在长链脂肪酸侧链末端将羧基（-COOH）替换为磷酸基（-PO₃H₂）。图2 GLP-1类药物结构演进与VK2735前药设计。从最初的GLP-1到Liraglutide（C16 单羧酸修饰）、Semaglutide（C18 二羧酸修饰）、Tirzepatide（C20 二羧酸 + 接头），多肽药物通过脂肪酸侧链延长半衰期、改善药代。Viking的VK2735则在长链脂肪酸末端引入磷酸基团（绿色虚线圈处），形成磷酸酯前药结构，用于显著提高口服生物利用度图片来源：作者整理（数据源：论文综述及专利搜索）如图所示从化学结构上看，VK2735包含一个GLP-1/GIP双激动肽骨架，连接着一条特殊的C19脂肪酰基侧链。这条侧链的末端不是传统的羧基，而是一个磷酸酯基团（-CH₂-O-PO₃H₂）。这个看似微小的改动，却带来了革命性的变化。这种设计的妙处在于"欲擒故纵"：磷酸酯基团就像给药物分子穿上了一件"隐身衣"，让它在胃酸的严酷环境中保持稳定，避免被胃肠道的蛋白酶快速降解。同时，磷酸基的极性特性大大提高了分子的水溶性，让原本"油水不相容"的肽类药物能够更好地溶解在胃肠液中。等到药物成功穿越胃肠屏障进入血液后，体内的磷酸酶会像"钥匙"一样，精准地"脱掉"这件保护衣，释放出具有生物活性的原形药物。这种"先保护，后释放"的策略，让VK2735既享受了前药的稳定性优势，又保持了活性药物的强效作用。值得一提的是，VK2735在口服制剂设计上还采用了SNAC作为促渗剂。这个配方看起来眼熟吗？没错，它几乎就是司美格鲁肽口服版的"孪生兄弟"。SNAC能够暂时性地打开肠道紧密连接，为药物分子开辟一条"绿色通道"，进一步提高口服生物利用度。图3 基于GLP-1长效改造策略汇总图片来源：EJMC论文综述这场关于VK2735的争论，本质上反映了现代药物开发的永恒命题：疗效与安全性的天平该如何平衡？但更重要的是，VK2735为我们展示了前药策略在解决复杂药物开发挑战中的巨大潜力。从技术角度来看，VK2735的磷酸酯前药设计为整个肽类药物口服化开辟了新的思路。这种"化学伪装术"不仅解决了肽类药物的胃酸稳定性问题，更为未来更多复杂生物大分子的口服给药提供了可借鉴的技术平台。可以预见，基于类似原理的新一代口服生物药将陆续涌现，彻底改变患者的用药体验。从产业角度来看，VK2735的出现验证了小分子前药策略的商业可行性，这将鼓励更多制药公司投入到口服生物药的研发中。同时，其在安全性方面遇到的挑战也提醒我们，技术创新必须与临床安全性紧密结合，这正是CDMO等专业服务机构发挥关键作用的领域。各个研究团队不同的前药策略则提醒我们，有时候最优雅的解决方案往往来自最精巧的分子设计。VK2735的故事告诉我们，在生物医药的创新道路上，每一次"不完美"的尝试都是通向完美解决方案的必要积累。癫痫治疗的钾通道密码：从失败中重新站起在神经科学的世界里，有一个关于钾通道的传奇故事正在续写新的篇章。故事要从十多年前说起。那时，英国制药巨头GSK推出了一款名为氯卡帕明（Potiga）的抗癫痫药，它是世界上第一个钾通道开启剂。这个药物的原理很巧妙：通过激活大脑中的Kv7钾通道，让过度兴奋的神经元"冷静下来"，从而控制癫痫发作。然而，好景不长。随着使用时间的延长，患者开始出现皮肤变色、视网膜色素沉着等令人担忧的副作用。2017年，Potiga黯然退市，钾通道疗法的第一次尝试以失败告终。但科学家们并没有放弃。加拿大的Xenon公司继续探索，声称通过结构改进解决了Potiga的问题，其新一代药物已进入III期试验。而丹麦Saniona公司的科学家们则认为，要想真正解决问题，需要更精准的"外科手术式"设计。他们发现了一个关键线索：Potiga之所以引发尿潴留等副作用，很可能是因为它"滥杀无辜"——不仅激活了治疗目标Kv7.2/7.3，还意外激活了Kv7.4/7.5。于是，他们设计了SAN2355这个"精准狙击手"：只激活Kv7.2/7.3，同时主动阻断Kv7.5，力求在保证疗效的同时最大化安全性。图4 25年8月，SAN2355独家授权Jazz，剑指癫痫及更多神经疾病图片来源：FierceBiotech新闻截图这个设计理念打动了美国Jazz公司。8月21日，Jazz豪掷4,250万美元拿下了SAN2355的全球开发权。公司研发主管Robert Iannone博士毫不掩饰自己的兴奋："这是一个独特且极具前景的候选药物，有望成为同类最佳。"分析师们更是大胆预测，选择性钾通道调控剂将开拓一个2030年规模达120亿美元的全新市场。不过话说回来，SAN2355目前还只是"纸上谈兵"，能否在人体中重现动物试验的美好前景，还需要时间来验证。癫痫是一种由大脑神经元网络过度兴奋引起的慢性脑部疾病，其背后往往伴随着抑制性神经回路的功能障碍。临床上，癫痫并非单一实体，而是一个异质性极高的疾病谱系，可被划分为局灶性发作（Focal）、全面性发作（Generalized）以及兼具或原因不明的类型。虽然市面上已有多种抗癫痫药物，但约有三分之一的患者对现有治疗不敏感，迫切需要新的作用机制。过去十年，研究者们逐渐关注到Kv7钾通道，尤其是Kv7.2/7.3亚型，它们在维持神经元膜电位稳定、抑制异常放电方面起着“刹车”的作用。早期药物如Retigabine虽验证了这一思路，却因缺乏亚型选择性导致尿潴留、皮肤色素沉着等副作用而被迫退市。正是在这样的背景下，SAN2355作为一款高度差异化、亚型选择性的Kv7.2/7.3激活剂进入视野——它不仅有望解决安全性瓶颈，还为癫痫及其他神经疾病的精准治疗提供了新的希望。表1 Saniona 癫痫内部管线概览候选物适应症当前开发阶段 SAN711 缺失性癫痫 Phase II 准备中 SAN2219 急性重复发作型癫痫临床前开发 SAN2355 难治性局灶性癫痫临床前候选药 / GMP 制备阶段资料来源：公开数据整理支气管扩张症的春天：首个特效药的诞生 2025年8月，对于全球数百万支气管扩张症患者来说，是一个值得铭记的历史时刻。这一天，美国FDA批准了Insmed公司的布伦索卡替布（Brensocatib），这是世界上第一款专门用于治疗非囊性纤维化支气管扩张症的药物。要知道，这种疾病虽然不算罕见，但长期以来只能"治标不治本"——抗生素、祛痰药、物理治疗，都只是在症状出现后"灭火"，却无法阻止疾病的根本进程。 Brensocatib的神奇之处在于它找到了疾病的"源头活水"。支气管扩张症的核心问题是中性粒细胞过度活跃，释放大量破坏性酶类，持续损伤肺部组织。而Brensocatib正是这些"破坏分子"的"总开关"——DPP1的抑制剂。通过阻断DPP1，它能从源头上切断中性粒细胞的"武装"，让炎症风暴平息下来。在关键的III期临床试验中，每天一粒Brensocatib让患者的年均急性加重次数减少了19-21%。这个数字看似不大，但对患者来说意义非凡——每一次急性加重都意味着咳血、呼吸困难、紧急住院，甚至生命危险。纽约大学的肺科专家Doreen Addrizzo-Harris教授激动地表示："这标志着我们治疗支气管扩张症方式的潜在范式转变。"患者组织更是欢呼这是"意义重大、期待已久的进展"。有趣的是，Brensocatib的成功还有一段"前世今生"的故事。这个分子最初诞生在阿斯利康的实验室里，代号AZD7986。但大公司往往"看山望山高"，最终将其授权给了专注于肺部疾病的Insmed继续开发。这也从侧面说明，有时候专业化的小公司比大而全的巨头更适合某些特定领域的深耕。图5 DPP1抑制剂主要专利持有公司以及化合物3D空间分布示意图图片来源：作者整理（数据源：Biofinder数据库）更值得一提的是，Brensocatib的成功是从失败中汲取教训的结果。GSK曾经开发过另一个DPP1抑制剂GSK2793660，但在II期试验中，10个患者里有7个在一周内就出现了严重的皮肤脱屑，项目不得不紧急叫停。相比之下，Brensocatib作为"可逆共价抑制剂"，安全性大幅改善，相关副作用发生率仅为1-4%。八月生物医药领域的三大案例为行业提供了重要启示：创新需要勇气，也需要稳健的科学设计和产业协同。减肥药VK2735暴露出疗效与安全性的矛盾，但其磷酸酯前药和SNAC促渗策略为口服肽类药物开发提供了可行范式。SAN2355的交易则昭示了精准离子通道调节剂的巨大潜力和资本市场的关注。未来，随着类似技术不断成熟，如何在疗效、安全性、商业价值之间取得合理平衡，仍将是药物开发者必须面对的永恒命题。 CDMO：创新药物背后的隐形英雄在这些激动人心的医学突破背后，有一群"隐形英雄"在默默发光发热——它们就是CDMO（合同开发与生产组织）公司。为VK2735这样的"娇贵公主"量身定制像VK2735这样的新型口服肽类药物，就像是"娇贵的公主"——既要保持活性，又要在胃酸的"酷刑"中存活下来。CDMO的制剂专家就像是"贴身保镖"，为它设计各种"防护装备"：SNAC渗透促进剂帮助它穿过肠壁，缓释工艺让它慢慢释放避免"一次性爆发"引起副作用。为SAN2355这样的"潜力股"铺路搭桥对于还在临床前阶段的SAN2355，CDMO更像是"全能管家"。从最初的合成路线设计（怎样最经济高效地制造这个分子），到中试放大（从毫克级到公斤级的华丽转身），再到制剂开发（做成什么样的胶囊或片剂最稳定），每一步都需要CDMO的专业护航。特别是对于涉及复杂手性结构的小分子，CDMO的化学家们需要在实验室里反复试验，就像调试精密仪器一样，确保每一个原子都在正确的位置上。为Brensocatib这样的"成功典范"保驾护航 Brensocatib的成功故事更是CDMO价值的完美诠释。从阿斯利康的实验室到Insmed的临床成功，再到FDA的批准，这条漫长的路上，CDMO像是"幕后英雄"：在早期，帮助优化合成工艺，让原本复杂昂贵的制造过程变得经济可行；在临床阶段，提供GMP级别的药物生产，确保每一批试验用药都符合最严格的质量标准；在上市前，协助准备厚厚的申报文件，满足监管部门的苛刻要求；在商业化阶段，建立大规模生产线，确保全球患者都能用上这救命的药。写在最后：创新与制造的共舞从VK2735的疗效争议，到SAN2355的精准设计，再到Brensocatib的历史性突破我们看到的不仅仅是医学科学的进步，更是整个医药产业生态的成熟。在这个生态中，有勇敢的科学家在实验台前挥汗如雨，有敏锐的投资者在风险与收益间权衡取舍，有严谨的监管者在安全与效率间寻找平衡，还有默默无闻的CDMO在幕后提供坚实的制造支撑。创新药的成功，从来不是某一家公司的独角戏，而是整个产业链的协奏曲。未来，随着更多突破性疗法涌现，随着个性化医疗时代的到来，CDMO的价值将进一步凸显。它们将不仅仅是"代工厂"，更将成为医药创新生态系统中不可或缺的"智慧节点"，连接着科学发现与患者获益的最后一公里。参考文献 1.BioPharma Dive. "Viking's VK2735 shows impressive weight loss in Phase 2, but tolerability concerns emerge." 2024. 2.FierceBiotech. "Jazz Pharmaceuticals acquires Saniona's epilepsy candidate SAN2355 for $42.5M upfront." 2024. 3.Insmed公司官方新闻稿. "Brensocatib获FDA批准用于支气管扩张症治疗." 2025年8月. 4.Nature Medicine. "DPP1 inhibition: A new paradigm for bronchiectasis treatment." 2025. 5.AMA Network Open 2025 关于 GLP-1 类药物停用与再启用的现实世界分析. *文章内容、封面首图及配图，版权归版权所有人所有。若版权者认为其作品不宜供大家浏览或不应无偿使用，请及时联系我们，本平台将立即更正。近期活动 2025医药行业合规数智创新论坛，9月23日 · 上海（点击查看） SHINE CONSULTANT 上海士研管理咨询有限公司成立于2005年，致力于为组织领导者提供沟通交流与专家智库平台。通过二十年沉淀与积累，覆盖了金融与投资、交通与运输、消费与文旅、医药与医疗、能源与资源、高科与电信、公用与政府等产业领域，服务着全球500强和万余家领导型企业，汇聚了百万余名机构决策者，并与千余家产业权威机构建立了战略伙伴关系。士研咨询秉承专业立身的理念发展队伍，现拥有百余名专业的资深人员，核心管理团队都具有十五年以上的专业经验。

2025-08-20

·FierceBiotech

Jazz pays Saniona $42.5M to add preclinical prospect to epilepsy ensemble

Jazz Pharmaceuticals will pay milestones as SAN2355 advances, starting with a $7.5 million fee tied to a phase 1 trial.\n Jazz Pharmaceuticals has struck a deal to bolster its epilepsy ambitions, paying Saniona $42.5 million upfront for a preclinical asset designed to address problems faced by GSK’s withdrawn drug Potiga.Dublin-based Jazz is on course to turn its existing epilepsy drug Epidiolex into a blockbuster this year. The Saniona deal gives the company global rights to the next-generation epilepsy drug candidate SAN2355. Saniona began (PDF) GMP manufacturing and toxicology studies for the asset in March, putting it on track to finalize a clinical trial application data package by the end of the year. Jazz will pay milestones as SAN2355 advances, starting with a $7.5 million fee tied to the initiation of the first phase 1 trial. The fee is part of $192.5 million in development and regulatory milestones included in the deal. Jazz is also on the hook for up to $800 million in commercial milestones based on product sales.SAN2355 is a selective small molecule activator of Kv7.2/Kv7.3 potassium channels. GSK’s Potiga showed that potassium channel openers can improve outcomes in patients with partial-onset seizures more than a decade ago, only for regulators to restrict use after reports of discoloration of the skin and retina. The company withdrew the product in 2017, citing (PDF) “very limited uptake” of the drug. Xenon Pharmaceuticals has advanced another potassium channel opener, azetukalner, into phase 3 trials in the belief that the structure of its molecule has fixed the problems that sank Potiga. But Saniona saw a need to go further, specifically by avoiding the Kv7.4/Kv7.5 activation it has identified as the likely driver of urinary retention seen in some recipients of azetukalner and Potiga.SAN2355 selectively activates Kv7.2/Kv7.3 while blocking Kv7.5, a design that Saniona has predicted will reduce urinary retention and adverse effects on the central nervous system. Equally, because SAN2355 is from a different chemical series than Potiga, the biotech sees little risk of skin and retinal discoloration. Convincing Jazz of the merits of SAN2355 gives Saniona its second deal in nine months. The biotech put cash into SAN2355 after licensing essential tremor candidate SAN711 to Acadia Pharmaceuticals for $28 million upfront last year.

临床1期临床3期引进/卖出

100 项与瑞替加滨相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09569	瑞替加滨	N03AX21	DB04953

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
癫痫部分性发作	欧盟	Glaxo Group Ltd.	2011-03-27
癫痫部分性发作	冰岛	Glaxo Group Ltd.	2011-03-27
癫痫部分性发作	列支敦士登	Glaxo Group Ltd.	2011-03-27
癫痫部分性发作	挪威	Glaxo Group Ltd.	2011-03-27

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
癫痫综合征	临床3期	美国	Xenon Pharmaceuticals, Inc.	2021-03-29
癫痫综合征	临床3期	澳大利亚	Xenon Pharmaceuticals, Inc.	2021-03-29
癫痫综合征	临床3期	比利时	Xenon Pharmaceuticals, Inc.	2021-03-29
癫痫综合征	临床3期	意大利	Xenon Pharmaceuticals, Inc.	2021-03-29
癫痫综合征	临床3期	西班牙	Xenon Pharmaceuticals, Inc.	2021-03-29
KCNQ2相关性癫痫性脑病	临床3期	美国	Xenon Pharmaceuticals, Inc.	2021-03-29
KCNQ2相关性癫痫性脑病	临床3期	澳大利亚	Xenon Pharmaceuticals, Inc.	2021-03-29
KCNQ2相关性癫痫性脑病	临床3期	比利时	Xenon Pharmaceuticals, Inc.	2021-03-29
KCNQ2相关性癫痫性脑病	临床3期	意大利	Xenon Pharmaceuticals, Inc.	2021-03-29
KCNQ2相关性癫痫性脑病	临床3期	西班牙	Xenon Pharmaceuticals, Inc.	2021-03-29

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04912856 (EPIK-OLE, CTgov)	临床3期	癫痫发作 \| KCNQ2相关性癫痫性脑病 \| 癫痫综合征	8	XEN496 (Group 1: XEN496 Treatment in Preceding Study)	鏇糧獵獵糧遞築鹽顧構 = 餘鹽鏇鏇壓壓鹹蓋醖廠築獵願積鏇淵簾夢醖餘 (齋襯獵鏇築窪鏇糧遞網, 選簾蓋鑰鏇簾餘構膚鹹 ~ 鏇壓憲夢網觸淵願觸齋) 更多	-	2025-02-14
				Placebo (Group 2: Placebo Treatment in Preceding Study)	鏇糧獵獵糧遞築鹽顧構 = 觸製壓襯觸鏇廠壓遞膚築獵願積鏇淵簾夢醖餘 (齋襯獵鏇築窪鏇糧遞網, 製艱顧鬱積選範選衊壓 ~ 膚淵鬱淵遞廠憲醖糧鑰) 更多
NCT04639310 (EPIK, CTgov)	临床3期	癫痫发作 \| KCNQ2相关性癫痫性脑病 \| 癫痫综合征	8	XEN496 (XEN496)	構衊襯窪顧廠壓鹹願衊(壓願遞鑰廠鬱構餘構選) = 襯簾鑰憲簾積鹽餘膚膚築淵餘窪選鑰夢獵願築 (襯憲蓋艱願蓋鑰醖顧憲, 23.49) 更多	-	2024-08-23
				Placebo (Placebo)	構衊襯窪顧廠壓鹹願衊(壓願遞鑰廠鬱構餘構選) = 淵繭築遞鹽製獵獵齋顧築淵餘窪選鑰夢獵願築 (襯憲蓋艱願蓋鑰醖顧憲, 46.84) 更多
NCT03043560 (CTgov)	临床2期	快感缺乏 \| 重度抑郁症	45	Ezogabine (Ezogabine)	糧鹽獵鹹願窪糧糧積積(艱餘艱積襯獵艱築鬱鏇) = 遞構衊築鹽憲鹽廠遞衊憲簾鬱鏇襯齋夢築壓夢 (觸鑰鑰簾蓋窪夢鑰襯襯, 0.69) 更多	-	2020-10-23
				Placebos (Placebo)	糧鹽獵鹹願窪糧糧積積(艱餘艱積襯獵艱築鬱鏇) = 鑰膚鹽範鹹簾淵淵構醖憲簾鬱鏇襯齋夢築壓夢 (觸鑰鑰簾蓋窪夢鑰襯襯, 0.79) 更多
NCT02450552 (CTgov)	临床2期	肌萎缩侧索硬化	65	Ezogabine (Oral Ezogabine 900 mg/Day)	衊製願餘鑰築簾衊製鹽(夢衊廠衊積製積範鬱糧) = 選壓積艱艱築衊製艱構構鑰製襯觸艱糧範醖糧 (廠廠蓋衊糧夢構艱顧製, 1.108) 更多	-	2019-08-28
				Ezogabine (Oral Ezogabine 600 mg/Day)	衊製願餘鑰築簾衊製鹽(夢衊廠衊積製積範鬱糧) = 鹽鏇糧鏇範鑰齋襯觸齋構鑰製襯觸艱糧範醖糧 (廠廠蓋衊糧夢構艱顧製, 1.302) 更多
NCT01777139 (CTgov)	临床3期	癫痫部分性发作	30	Retigabine IR	艱選範衊範壓積觸壓構(範鬱鑰壓壓網醖膚築願) = 構遞願窪艱鹽願構築網蓋遞廠艱蓋憲選獵網鏇 (製繭構範網蓋製窪築鹹, 2.68) 更多	-	2019-04-22
NCT02149836 (CTgov)	临床2期	重度抑郁症	18	ezogabine	憲選製範網膚憲鏇膚獵(選繭鑰願築網簾醖願廠) = 鹹築壓鹹範顧餘鑰鏇製醖鬱糧遞壓衊鬱衊蓋獵 (蓋獵衊觸衊糧網廠鏇夢, 4.93) 更多	-	2019-04-16
NCT00310388 (CTgov)	临床3期	癫痫部分性发作	376	Retigabine (Retigabine)	構夢鏇膚糧窪糧鹹選選 = 獵範簾淵鏇窪壓衊襯鹹遞壓齋餘遞夢獵膚廠憲 (糧餘顧鹽觸範獵齋衊廠, 築製醖壓鹹積壓淵鏇製 ~ 壓淵窪憲遞鬱製艱獵衊) 更多	-	2018-06-06
				retigabine (SFUCP)	淵憲鏇繭壓艱餘餘窪繭 = 鹽築窪衊積構選糧簾積艱艱製鬱遞鬱淵蓋網襯 (選醖憲範選選願鏇淵繭, 願衊網繭鑰鹹積選構膚 ~ 鹹積壓積醖願淵願艱艱) 更多
NCT01336621 (IR, CTgov)	临床3期	癫痫部分性发作	98	Retigabine IR	齋鑰網蓋觸選鹹襯餘製 = 積願蓋築鹽築廠選構築壓鏇廠蓋壓憲夢醖醖夢 (觸膚鬱積鬱齋繭鹹獵艱, 憲膚簾膚鹽齋獵糧遞網 ~ 網憲構鹽艱構糧獵範選) 更多	-	2018-02-26
NCT01607346 (CTgov)	临床4期	癫痫部分性发作	10	ezogabine/retigabine	鬱餘壓淵遞餘艱遞糧鹽(艱遞願艱鹽構積膚鑰繭) = 壓廠鹽製淵憲積獵鏇顧艱膚齋鹹壓選醖艱構製 (艱鏇衊窪蓋選顧餘鑰鏇, 4.797) 更多	-	2017-09-26
IEC2017	N/A	-	-	Lamotrigine	艱鹹構鹽衊遞夢壓齋餘(壓壓餘淵淵網齋蓋蓋鹽) = Levetiracetam was poorly tolerated in 9% of patients due to psychiatric side effects 鹽鏇鹽齋繭範艱夢鹹觸 (遞艱願鑰選構鏇淵選構 ) 更多	-	2017-09-03
				Retigabine