Birch triterpenes

The FDA has so far approved four botanical products, with a view to greenlight more. Credit: Svetliy/Shutterstock.com. The US Food and Drug Administration (FDA) is requesting public input on both the opportunities and challenges regarding drugs derived from botanical sources. Botanical drug products are those developed from one or a combination of plants, algae, or macroscopic fungi. While there are approved drugs in this class, their complexity means research and development (R&D) is more difficult than traditional therapy modalities. Via a request for information (RFI), the FDA wants to find out more about the challenges encountered in botanical R&D from researchers, clinicians, and others in the pharma industry. Respondents are also encouraged to share innovative approaches they are using in the space, along with how they design studies and utilise real-world evidence (RWE). The FDA’s aim is to provide a modernised regulatory framework to expand on the four currently approved botanical products. MediGene’s Veregen uses sinecatechins from green tea leaves for the treatment of genital and perianal warts; Napo Pharma’s antidiarrheal Mytesi is based on the red sap of the South American lechleri tree; Chiesi’s Filsuvez is a prescription topical gel made from birch bark extract for wound treatment. The fourth, approved via a biologics license application (BLA), is NexoBrid (anacaulase-bcdb), which is derived from a mixture of enzymes found in pineapples. There is also a wealth of over-the-counter (OTC) botanicals that are popular for home management of certain conditions, which the FDA highlights as evidence of public interest in the products. “Given that many people use botanicals for self-treatment, botanical drug products represent an area where greater scientific development could create new opportunities for patients,” said Marta Sokolowska, deputy center director for substance use and behavioural health in the FDA’s Center for Drug Evaluation and Research (CDER). Investing time to modernise regulatory pathways for botanical drug products is one of many strategies being carried out by the US administration in efforts to diversify modalities of approved therapies. For example, Trump’s administration has provided enhanced frameworks for psychedelics designed for mental health conditions. “Under the Trump Administration, we are committed to modernising regulatory frameworks to ensure promising, natural health options are evaluated through rigorous science,” said acting FDA Commissioner Kyle Diamantas. “Botanical drug products represent a critical area where greater scientific development can unlock new therapeutic opportunities for American patients while maintaining the highest safety standards,” he added. The public docket comes soon after a report by climate research group Zero Carbon Analytics demonstrated the therapeutic value of tropical rainforests . According to the group, protecting tropical forests – that harbour plants, fungi and microbes used in drug development – could offer between $382bn and $1.2tn in value for the pharmaceutical industry.

站在2026年时间节点回望，渐冻症（ALS）药物研发正处于一个充满希望又伴随阵痛的关键时期。基因靶向疗法打开了“解冻”的大门，但距离彻底治愈，我们仍有一段漫长的路要走。一、疾病基础：数字背后的残酷现实 全球约有35-50万ALS患者，中国占5-10万，确诊后中位生存期仅2-5年。其中80-90%为散发性ALS——这是目前最大的医学难题。遗传型仅占10-20%，主要涉及SOD1、C9orf72、FUS等基因突变。 过去的传统药物如利鲁唑、依达拉奉，只能有限延缓病程，无法阻断疾病进展。二、核心主线：基因靶向疗法正在成为“解冻”主力 基因药物的核心逻辑是“沉默致病基因” ，主要分两类：ASO（反义寡核苷酸）和siRNA（小干扰RNA）。以下是当前最值得关注的三大管线：1. Tofersen（Qalsody）——已上市，打开基因治疗大门 全球首个获批的ALS基因靶向药（2023年FDA加速批准） 针对SOD1基因突变型，鞘内注射 2026年长期数据证实可延缓进展 局限：仅覆盖约2%患者，费用高昂，需定期腰穿2. RAG-17（国产siRNA）——跑出中国速度 全球首个中美同步获批临床试验的ALS疗法 机制：siRNA沉默SOD1，已有FUS亚型见效信号 I期数据发表于《Nature Medicine》，II期已完成入组 2026年底关键数据读出，最快2028年有望获批 注意：“小刘站起来”等个案振奋人心，但不等于临床结论，最终有效性需看II/III期大样本数据3. 力图攻克的散发性ALS 目前针对占患者群体80-90%的散发性ALS，全球尚无获批的靶向药物。但多条技术路线正在同时推进，力图攻克这一难关： 靶向错误折叠蛋白：如AL-S Pharma的AP-101（单克隆抗体）在包含散发性ALS患者的II期试验中取得积极结果，计划2027年推进III期。 恢复脂质代谢：Leal Therapeutics的LTX-002（ASO）旨在恢复中枢神经系统脂质代谢，已进入I/II期。 降低TDP-43水平：NeuroSense的PrimeC在IIb期试验中显著降低了TDP-43蛋白水平，已获FDA批准推进III期。VectorY的VTx-002（载体化抗体）也已进入I/II期。 小分子与免疫调节：Nura Bio的SARM1抑制剂NB-4746、CervoMed的Neflamapimod等小分子药物，以及调节性T细胞疗法、低剂量IL-2等免疫调节疗法均在探索中。 此外，HEALEY ALS平台试验等也在持续评估多种在研药物。这些研究大多处于早期阶段，距离获批上市仍有相当距离。三、不可回避的失败教训——“新药三堂课” ALS新药研发失败率极高，以下案例值得深刻铭记：AMX0035 2022年加速批准，曾被寄予厚望，后续III期试验失败，2024年撤市。教训：加速批准≠最终胜利，III期才是“照妖镜”。NurOwn（干细胞疗法） III期未达终点，FDA拒绝批准。教训：细胞治疗在ALS中仍很早期，不能盲目乐观。BIIB078（针对C9orf72） 临床试验无获益，直接停止。教训：靶点正确≠药物有效。 共同启示： ALS异质性极强，小样本希望不等于大样本成功 AMX0035撤市后，全球监管审批门槛大幅提高 个案效果不能等同于对所有人有效，必须理性管理预期四、多维武器库：不止基因药物 除了基因疗法，多条路线同步探索： 小分子/免疫药物：masitinib、托珠单抗等，尚在试验阶段 BCI脑机接口：不能治病，但能让晚期患者恢复沟通——“让冻住的人先说出来”，是另一种“解冻” 细胞治疗：正在吸取NurOwn失败经验，迭代再出发 五、给患者家属的实操建议 基因检测是关键的第一步——相当于新疗法的“入场门票”，有家族史或已确诊者尽早检测 SOD1突变型可关注Tofersen和RAG-17 区分“媒体个案”与正式临床数据，不盲目神化 全病程重视多学科管理：呼吸支持、营养管理、康复训练 晚期可关注BCI等沟通辅助技术六、结语 Tofersen开了门，RAG-17跑起来，QRL-201在路上——基因靶向时代已经到来。但ALS的“解冻”不等于“治愈”，更多意味着延缓进展和部分功能改善。AMX0035的撤市提醒我们，科学进步从来不是一条直线。 曙光在前，道路曲折，我们正走在正确的方向上。 免责声明：本文仅供ALS科研信息交流与科普参考，不构成任何医疗建议或用药指导。文中涉及的在研药物数据来源于公开文献及行业研报，具体治疗方案请咨询专业医师。 调研来源： 《Nature Medicine》RAG-17 I期临床研究（2026.7） WashU Medicine Tofersen长期随访数据（2026） QurAlis公司QRL-201公开管线信息 NEALS官方网站 FDA/EMA公开监管记录及ClinicalTrials.gov登记信息 ALS Association / PMC12423166（Quigley 2025） 北京日报、新京报、上观新闻等公开报道（2026）