An Interventional, Prospective Open-Label Study of Immunosuppressive Therapies to Mitigate Immune-Mediated Loss of Therapeutic Response to Asfotase Alfa (STRENSIQ®) for Hypophosphatasia (RESTORE)

The primary objective of this study is to evaluate the effect of immunosuppressive therapy (IST) in participants treated with asfotase alfa who demonstrate immune-mediated loss of effectiveness (LoE).

开始日期2026-07-29

申办/合作机构

Alexion Pharmaceuticals, Inc.

NCT07113158

/ Not yet recruiting临床3期IIT

Effect of Aspirin and Folic Acid for Sudden Sensorineural Hearing Loss

The annual incidence of sudden sensorineural hearing loss (SSNHL) is 5 to 20 per 100 000 persons. The pathophysiology of SSNHL and acute vestibulo-cochlear syndromes (VCS) is unknown in more than 70% of cases.
Hypothesis : an inner ear microvascular disease represents the key element in the pathogenesis of SSNHL and acute VCS.
Plasma serotonin has among other tissular effect a vasospastic on microcirculation such as the inner ear microvascularisation. Increased plasma homocysteine has a deleterious effect on vascular endothelium. Inner ear microvascularisation sensitized by an increased homocysteine level and the vascular wall would vasoconstrict under serotonin stimulation inducing ischemia of the vestibular and/or cochlear organs.

开始日期2026-04-01

申办/合作机构

Assistance Publique des Hôpitaux de Paris SA

NCT07377071

/ Not yet recruiting早期临床1期IIT

Impact of Folate Administration on One-Year Mortality in Patients With Infection-Associated Acute Kidney Injury: An Open-Label Randomised Controlled Study

The goal of this clinical trial is to evaluate if taking folic acid (a form of vitamin B9) can help reduce the risk of death and improve kidney recovery in adults with acute kidney injury (AKI) caused by infections or sepsis.
The main question it aims to answer is: Does taking folic acid lower the chance of dying within one year for these patients? This study will also look at other important questions, such as whether folic acid helps kidneys recover faster (within 7 days), prevents long-term kidney problems (progression to chronic kidney disease at 3 months), reduces heart-related events, and is safe.
Researchers will compare the group receiving folic acid (5 mg taken by mouth once daily for 90 days, plus usual care) to the group receiving only usual care (standard treatments like fluids, blood pressure control, antibiotics, and stopping harmful medicines) to see if folic acid provides extra benefits.
Participants will:
1. Be randomly assigned to one of the two groups
2. Receive usual hospital care for their infection and AKI
3. Take the folic acid (or not, depending on their group) every day for 3 months
4. Have blood tests at the start and at 3 months (including to check serum folate levels)
5. Be followed up for 1 year through clinic visits, phone calls, or medical records to track health outcomes like survival, kidney function, and any side effects
This open-label study (both patients and doctors know which treatment is given) will include about 382 adults at Queen Mary Hospital in Hong Kong. It builds on earlier retrospective study data suggesting folic acid might improve survival in similar patients.

开始日期2026-04-01

申办/合作机构

香港大学

100 项与叶酸相关的临床结果

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100 项与叶酸相关的转化医学

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100 项与叶酸相关的专利（医药）

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47,345

项与叶酸相关的文献（医药）

2026-12-31·ANNALS OF MEDICINE

Machine learning-based risk factors for acute-on-chronic liver failure in alcohol-associated liver disease

Article

作者: Liangpunsakul, Suthat ; Hu, Linhui ; Cheng, Hao ; Wang, Yan ; Pan, Jing

BACKGROUND:

In patients with alcohol-associated liver disease (ALD), heavy and prolonged alcohol consumption can trigger acute-on-chronic liver failure (ACLF), a condition associated with high early mortality and significant clinical challenges. Early identification of patients at risk is critical for improving outcomes.

AIMS:

We conducted a retrospective observational study of patients diagnosed with ALD between January 2000 and December 2024 to develop a predictive model for ACLF.

METHODS:

Key clinical indicators were selected using LASSO-regularized logistic regression (LR). The final LR model was visualized as a nomogram and compared with four additional machine learning algorithms. Model performance was evaluated using ten-fold cross-validation and area under the curve (AUC), while feature importance was assessed with Shapley Additive exPlanations values.

RESULTS:

Among 210 patients with ALD, LASSO identified four independent predictors of ACLF: total bilirubin (TBIL), folate, vitamin B12 (VitB12) and the difference from the normal value of prothrombin time (ΔPT). The LR model achieved an AUC of 0.970, indicating excellent predictive accuracy.

CONCLUSION:

We developed a robust clinical prediction model combining LR and machine learning approaches. TBIL, folate, VitB12 and ΔPT are key prognostic markers that may enable early risk stratification and timely intervention, potentially reducing ACLF incidence in ALD patients.

2026-12-31·DRUG DELIVERY

Folate-targeted gold nanoparticles for doxorubicin delivery in tumor spheroids

Article

作者: Daniele, Raffaella ; Caliceti, Paolo ; Salmaso, Stefano ; Marzaro, Giovanni ; Fragassi, Agnese ; Pesce, Cristiano ; Tognetti, Francesco ; Verona, Marco

Targeted drug delivery systems represent a promising strategy for enhancing the efficacy and specificity of cancer therapy. In this study, 35 nm folate-targeted gold nanoparticles are presented as nanoparticle-drug conjugates obtained by anchoring on their surface lipoyl terminating doxorubicin prodrug (proDoxo) releasable at the endolysosomal acidic pH to prevent off-site toxic effects. Colloidal stable nanoparticles with a density of proDoxo up to 1000 molecules/particle and 2 kDa mPEG-SH coating were obtained. At pH 5, Doxo was completely released from the nanoparticles in 5 days while only 13% was released over the same period at pH 7.4. The nanoparticle decoration with folic acid as a targeting agent bestowed nanosystems with selective drug delivery to folate receptor (FR)-overexpressing cancer cells and controlled intracellular release. This led to enhanced cancer cell killing by folated nanoparticles compared to their nontargeted counterparts. Moreover, folated nanoparticles were found to distribute more homogeneously inside KB^FR+ cancer cell spheroids than non-targeted nanoparticles, resulting in higher spheroid volume reduction.

2026-12-01·JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN

In vitro and in silico studies of anticancer activities of pectic acid and pectin oligosaccharide in Epstein-Barr virus-positive nasopharyngeal carcinoma

Article

作者: Mohan, Darshini ; Murugaiyah, Vikneswaran ; Teh, Aik-Hong ; Yap, Beow Keat ; Khor, Boon-Keat

Pectic acid (polygalacturonic acid, PGA) and pectin oligosaccharides (POS) have shown selective anticancer activities with cytotoxicity against various cancer cells, including breast adenocarcinoma MCF-7. While promising, their anticancer activities against the nasopharyngeal carcinoma (NPC) have yet to be determined. To this end, the antiproliferation activities of pectic acid and enzymatically derived unsaturated POS trimer were investigated against the EBV-positive NPC cell line, C666-1, as well as on MCF-7 (as positive control) and NIH-3T3 cells (as non-tumorigenic cell model). Our study shows that both POS trimer and PGA can inhibit C666-1 cells' proliferation at concentrations above 20 mg/mL and 2.5 mg/mL, respectively. Previous studies had also demonstrated that one of the key biological targets for these compounds is the human galectin-3 (hGal3). However, the binding mode of pectic acid and the unsaturated POS trimer to human galectin-3 is still lacking. To investigate this, in silico molecular docking and all-atom molecular dynamics simulations were performed. Analysis of the MD trajectories revealed that the unsaturated POS trimer prefers binding to hGal3 oligomer over hGal3 monomer with a ligand: protein monomer ratio of 1:2 and 1:3. On the other hand, both hGal3 monomer and dimer were found to bind stably to the POS 15-mer (as PGA model) along its linear chain throughout the simulation. In conclusion, both unsaturated POS trimer and PGA have the potential to be novel anticancer agents against EBV-positive NPC, though further development to increase their potency and/or selectivity would be necessary.

752

项与叶酸相关的新闻（医药）

2026-03-17

·BioSpace

What the Leucovorin Approval Signals—or Doesn’t—About the FDA’s Rare Disease Stance

FDA Commissioner Marty Makary speaks at a White House press conference on September 22, 2025. / Joyce N. Boghosian, White House Although FDA Commissioner Marty Makary promised “an exciting treatment” for autism, what the agency delivered was a label expansion for leucovorin to treat the ultrarare cerebral folate deficiency. The regulatory process, which relied on a literature review rather than new evidence, stands in contrast to recent rare disease rejections in which the FDA cited a need for more rigorous evidence. FDA observers have noted a disconnect between what agency officials say about the need for regulatory flexibility when considering therapeutics for rare diseases, and a string of rejections of just such candidates. UniQure, for example, has weathered not only a complete response letter (CRL) but also public criticism from FDA officials for attempting to win approval based on an externally controlled pivotal trial. RENENXBIO, Biohaven and Capricor Therapeutics have also received CRLs over the past year. Sen. Ron Johnson (R-WI) has launched an investigation into such rejections. In sharp contrast to these stories, the FDA last week touted its expansion of leucovorin—long approved to ameliorate the effects of certain cancer therapies—to treat cerebral folate deficiency (CFD) linked to a particular genetic variant, an action it said “reflects the agency’s commitment to accelerating cures and expanding treatment options including for patients with serious and unmet needs.” Notably, the expansion was initiated not by a drug company but by the FDA itself after Commissioner Marty Makary promoted leucovorin as a treatment for autism. Agency staffers mined the literature for evidence of leucovorin’s effectiveness in CFD. Unsurprisingly for a disease that has been diagnosed in fewer than 50 people worldwide, that evidence does not include a randomized, controlled trial. The apparent discrepancy in evidence standards “can’t be rationalized in a coherent sense, other than that leucovorin is a drug that is being shaped to fit RFK’s agenda around autism and it’s outside the reach of Vinay Prasad and [the Center for Biologics Evaluation and Research],” Holly Fernandez Lynch, a bioethics and law professor at the University of Pennsylvania, wrote in an email to BioSpace . “This is exactly the sort of thing that makes the public not trust FDA’s decisions, as this is not based in science, it’s based in politics.” The decision “is highly unusual—maybe unprecedented—and I think it’s good and bad,” said Paul Kim, principal at Kendall Square Policy Strategies and a former FDA counsel to the late Senator Edward Kennedy and Congressman Henry Waxman. While the regulatory approach of mining real-world evidence could benefit other rare diseases, Kim agreed there is a political story behind the expansion. A Tenuous Autism Link On Sept. 22, 2025, as part of a White House press conference in which President Donald Trump and members of his administration alleged a link between autism and Tylenol exposure in utero, FDA chief Marty Makary took the podium to deliver what he called good news. “Today, the FDA is filing a federal register notice to change the label on an exciting treatment called prescription leucovorin so that it can be available to children with autism,” he said. “We have a duty to let doctors and the public know. . . . Hundreds of thousands of kids, in my opinion, will benefit.” This came after then–Center for Drug Evaluation and Research Director George Tidmarsh had asked FDA staff in August to look into finding a way to approve leucovorin for autism, STAT News later reported. The drug, a form of folic acid, was originally sponsored by GSK and used to ameliorate the effects of cancer drugs such as methotrexate and fluorouracil. It’s been used off-label to treat CFD since 2009, an expert on the condition told CNN . GSK no longer makes the drug, but some generic suppliers do. CFD has some overlap in symptoms with autism, and a few small studies have explored leucovorin’s use in the more common condition. But according to the American Academy of Pediatrics , “Current evidence is insufficient to support prescribing leucovorin for autism in the absence of CFD.” Tidmarsh and FDA staffers ultimately compromised with a plan to submit leucovorin for approval in CFD rather than autism, STAT reported. GSK reviewed the case reports provided by the FDA and submitted the supplemental New Drug Application to update the indication, a company spokesperson told BioSpace in an email, though it does not plan to resume making or marketing the brand-name version of the drug. At the September press conference, Makary blurred the distinction between CFD and autism and discussed a possible mechanistic link between folate and autism. Policy and regulatory consultant Steven Grossman speculated that leucovorin’s approval for CFD may make the drug materially easier to access for autism as well. “[If] you’re a pediatrician and you’re under pressure from parents—and I’m sure they are—to prescribe leucovorin [for autism] because of the noises coming out of HHS,” the drug’s recent label expansion may make it easier to justify, he suggested. It would still be an off-label prescription but it would be for a drug that’s approved for a pediatric disease and not just for cancer. “While there may be more going on,” Grossman said, “the whole deal looks very much like a gigantic ‘wink-wink’ from the administration.” A Glimpse of What Could Be As Kim sees it, with the press conference and what followed, “we get this highly unsatisfactory, patient-adverse lifting of expectations and crashing of them with the announcement on CFD.” Yet for him, the episode points to what’s possible, namely that “many, many very rare diseases . . . could benefit from this approach” of mining real-world evidence. With more research funding and needed infrastructure in place, “I would be not surprised to see multiple approvals of very rare disorder therapies like leucovorin, either repurposed or novel ones, and a real renaissance,” Kim said—one that is not dependent on the financial markets or emerging company formation but rather taps into the ongoing work of academics and clinicians. As it stands, he said, the leucovorin label expansion is “like hanging a Christmas ornament high on the tree, but there’s nothing else on the tree.”

上市批准

2026-03-16

·罕见病信息网

10款罕见病药物迎新进展；2026全国两会代表委员罕见病提案汇总；第三届中国罕见病科研大会6月在沪举办 | 壹周罕见药闻

罕见病信息网隆重推出《壹周罕见药闻》这一独具特色的品牌栏目。该栏目在每周一更新，以呈现上周罕见病领域的最新消息并同步近期重要活动预告。我们以更高端、更权威的视角，为您剖析最新、最热门的罕见病信息。罕药快讯 01 5款新药首进Ⅲ期，2月全球统计据罕见病信息网统计，2026 年 2 月，全球共有 5 款新药首次进入临床 Ⅲ 期，其中包括 I 型神经纤维瘤病 - 丛状神经纤维瘤、A 型血友病、Stargardt 病等罕见病适应症。 02 6款罕见病药物终止研发据罕见病信息网统计，2026年2月有6款罕见病药物终止研发，其中包括多发性硬化、骨髓增生异常综合征、家族性寒冷自身炎症综合征等罕见病适应症。 03 恒瑞口服1类新药获批初治重型再生障碍性贫血（SAA） 3月13日，NMPA 官网显示，恒瑞1类新药「海曲泊帕乙醇胺片」获批一项新适应症，联合免疫抑制治疗，适用于15岁及以上初治重型再生障碍性贫血（SAA）患者。此次获批是基于一项多中心、随机、双盲、安慰剂对照、 III 期临床试验（HR-TPO-SAA-Ⅲ）的积极结果。该试验旨在初治重型再生障碍性贫血患者中评价海曲泊帕乙醇胺片联合标准免疫抑制治疗的有效性和安全性。 04 亚叶酸钙片在美获准用于治疗脑叶酸转运缺乏症 3月10日，美国食品药品监督管理局(FDA)宣布已批准扩大葛兰素史克公司的Wellcovorin（leucovorin calcium，亚叶酸钙）片剂的使用范围，用于治疗患有脑叶酸缺乏症且叶酸受体1基因(CFD-FOLR1)存在已确认的变异的成人和儿科患者。新闻稿指出，Wellcovorin是首个治疗罕见FOLR1相关脑叶酸缺乏症的药物。亚叶酸钙是一种能够穿透血脑屏障的叶酸衍生物，因此有望有效缓解中枢神经系统的叶酸缺乏问题。 05 新型DMD基因疗法I/II期临床积极数据发布近日，Regenxbio公司在2026年肌肉萎缩症协会 (MDA) 临床与科学会议上发布了其针对杜氏肌营养不良症 (DMD) 的在研AAV基因疗法RGX-202关键性临床试验AFFINITY DUCHENNE的积极中期数据。数据显示，这款潜在同类最佳 (best-in-class) 基因疗法在给药一年后不仅在运动功能和心脏健康方面展现出显著的稳定和改善作用，其安全性数据也异常亮眼。公司计划于2026年年中申请FDA的BLA前会议，确证性试验同步顺利推进，已进入商业化倒计时阶段。 RGX-202是一款基于AAV8载体的潜在同类最佳 (best-in-class) 基因疗法，搭载肌肉特异性启动子Spc5-12，旨在递送表达微肌营养不良蛋白的转基因进入骨骼肌和心肌组织，改善杜氏肌营养不良症患者的肌肉功能和预后。 06 特发性肺纤维化 (IPF) 创新疗法获FDA孤儿药资格认定近日，Nuformix公司宣布，其用于治疗特发性肺纤维化 (IPF) 的在研潜在同类最佳 (Best-in-Class) 雾化吸入式疗法NXP002已获得美国FDA授予的孤儿药资格认定 (ODD)。这一里程碑进展，不仅为这种高致死率疾病带来了新希望，更展示了雾化给药在呼吸道疾病治疗中的巨大临床优势。 NXP002的核心活性成分为曲尼司特 (Tranilast)，Nuformix公司通过配方创新将其重塑为吸入式递送剂型，药物颗粒能够随呼吸直接进入下呼吸道和肺泡实质也限制了药物向外周血液的渗透。这种直达病灶的设计，有望在提高肺部局部药物浓度的同时大幅降低系统性暴露带来的毒副作用风险。 2025年4月，NXP002已获得欧盟EMA授予的孤儿药资格认定。与此同时，曲尼司特作为一种在中国、日本和韩国已被广泛用于治疗支气管哮喘、特应性皮炎和瘢痕的临床安全药物，具备良好的应用基础，安全性已得到临床验证，这为其向IPF治疗领域的转化应用提供了现实可行性。 07 法布雷病基因疗法冲刺“加速批准通道”上市近日，Sangamo Therapeutics公司宣布，其用于治疗成人法布雷病的AAV基因疗法ST-920在关键STAAR研究 (NCT04046224) 中成功证实了对肾功能的保护作用，已向美国FDA正式提交了生物制品许可申请 (BLA) 的临床与临床前模块，正在通过“加速批准通道”全速冲刺上市！ ST-920 (Isaralgagene Civaparvovec) 是一种利用AAV2/6载体将优化后的肝脏特异性启动子元件驱动的能性GLA基因导入肝脏的基因疗法，旨在使患者肝细胞能够持续产生并分泌α-Gal A酶，从而纠正潜在的生化缺陷，有望从根本上解决酶缺乏的问题，有望实现“一次治疗，长期获益”的终极目标。此前，ST-920已获得美国FDA的孤儿药资格认定 (ODD)、快速通道认定 (FTD) 和再生医学先进疗法资格认定 (RMAT)，以及欧洲药品管理局 (EMA) 授予的孤儿药资格认定 (ODD) 和优先药品资格认定 (PRIME)，以及英国MHRA的创新许可和准入途径资格认定 (ILAP)。 08 Vertex突破性疗法3期临床结果积极近日，Vertex Pharmaceuticals公司宣布，其正在进行的3期临床试验RAINIER在预先设定的第36周中期分析中获得积极数据。该试验旨在评估在研疗法povetacicept在免疫球蛋白A肾病（IgAN）中的疗效与安全性。新闻稿指出，Vertex预计在3月底之前完成生物制品许可申请（BLA）的滚动提交，寻求潜在加速批准。 Povetacicept总体安全性和耐受性良好。大多数不良事件（AE）为轻至中度。试验中未出现与povetacicept相关的严重不良事件（SAE），也未出现死亡病例。未观察到机会性感染，也没有因感染导致的停药情况。与预期一致，试验中检测到抗药抗体（ADA），但这些抗体未对疗效或风险特征产生影响。 09 血霁生物的巨核细胞注射液10天分别获批NMPA和FDA两个IND 3月13日，苏州血霁生物自主研发的全球首个同种异体巨核细胞注射液，获美国FDA新药临床试验（IND）批准，适应症覆盖各类病因所致血小板减少症，普适性与市场潜力突出，这也是公司第二款在FDA获批的药物。该款药物此前已获中国CDE两项临床试验许可，3月3日获批第二个适应症，此次FDA批件为血霁生物10天内斩获的第二个IND批件，实现中美药监双认可。作为全球首创品种，其可快速且长效提升血小板数量，兼具成本低、安全性高、无基因编辑、无明显副作用及血栓风险等核心优势。下一步，血霁生物将全力推进国内两项临床试验，并计划于2026年第三季度启动Pre-IPO轮融资，助力这款全球原创血小板新药加速落地。 10 新数据公布，罕见病基因治疗赛道再添重磅成果 3月12日，Ultragenyx公司宣布，其AAV8载体基因疗法DTX301，在治疗鸟氨酸氨甲酰基转移酶缺乏症（OTCD）的Ⅲ期Enh3ance试验中取得积极顶线结果，血氨控制疗效显著，为这类亟需根治方案的罕见尿素循环障碍疾病带来里程碑式治疗希望。 11 多重国际认证加持环码与 Vertex 临床双双突破 3月11日，上海环码生物医药有限公司宣布，其自主研发的第二款核心环形RNA创新药物 HM2003 注射液迎来重磅突破，正式获得美国食品药品监督管理局（FDA）临床试验许可（IND）。同时，HM2003针对某未披露适应症获得了FDA的儿科罕见病药物认定（RPDD）。此前，该产品已获得针对血栓闭塞性脉管炎（TAO）的孤儿药资格认定（ODD）。HM2003 IND获批叠加双项特殊资格认定，成为该产品全球临床开发的重要里程碑，也进一步彰显环码生物环形RNA技术平台的国际竞争力。 12 每周一针更轻松，这款罕见病创新药离中国患儿又近一步 3月10日，国家药品监督管理局药品审评中心（CDE）官网公示，维昇药业递交的注射用那韦培肽（商品名：Yuviwel®）拟纳入优先审评，其适应症为用于治疗2岁及以上骨骺未闭合的软骨发育不全儿童患者。此举标志着这款针对罕见遗传病的创新疗法在中国上市进程迈出关键一步。 13 覆盖19种罕见病！2月全球20款新药获批上市据罕见病信息网不完全统计，2026年2月全球有20款罕见病药物获批上市，覆盖进行性家族性肝内胆汁淤积症、骨巨细胞瘤、软骨发育不全、重症肌无力等19罕见病。罕圈动态 01 奥妥珠单抗β治疗视神经脊髓炎谱系疾病（NMOSD）国内首方落地 3月11日，用于治疗视神经脊髓炎谱系疾病（NMOSD）的新型生物制剂的首张处方迅速开出。解放军总医院第一医学中心神经免疫亚专科主任黄德晖教授，解放军总医院第一医学中心眼科医学部主任医师魏世辉教授，作为首批处方专家，让这款突破性创新药物第一时间触达临床需求；专家们也第一时间发声点评，共同见证我国NMOSD治疗迈入新时代。此举为缺乏有效治疗方案、深受疾病复发困扰的NMOSD患者带来了新的希望，为推动神经免疫性疾病精准诊疗事业发展进程中写下里程碑式的一笔！ 02 2026全国两会代表委员罕见病提案汇总，哪条提到你心坎上了？ 3月12日下午三时，十四届全国人大四次会议在人民大会堂闭幕。近年来，罕见病已然成为两会讨论的热点之一。罕见病相关提案、议案为医疗保障与药物可及性、科研与药物研发支持、产业推动、社会认知与患者权益保护带来了重大价值。据罕见病信息网统计，今年有至少15位人大代表、政协委员提交了罕见病相关建议，涵盖制度保障、科技创新、产业发展等不同方面。 03 融资2.4亿美元！致力开发AAV基因疗法近日，致力于开发神经肌肉和心脏疾病精准基因药物的生命科学公司Solid Biosciences（Nasdaq:SLDB）宣布已与一批精选的机构认可投资者签署证券购买协议，在扣除配售代理费和发行费用之前，将进行约2.4亿美元的私募配售，预计将于2026年3月9日左右完成，前提是满足惯例的结束条件。公司计划将此次私募的净收益用于资助正在进行的管线开发项目、业务拓展活动，以及作为营运资金和其他一般公司用途提供资金。 Solid Biosciences是一家专注于精准基因疗法的公司，致力于推进针对罕见神经肌肉和心脏疾病的基因治疗候选药物组合，包括治疗杜氏肌营养不良症（Duchenne）的SGT-003、治疗弗里德赖希共济失调（FA）的SGT-212、治疗儿茶酚胺敏感性多形性室性心动过速（CPVT）的SGT-501、治疗TNNT2介导的扩张型心肌病及其他致命性遗传性心脏疾病的SGT-601。该公司还致力于开发创新的基因调控元件库及其他赋能技术，这些技术有望对跨行业的基因治疗递送产生重大影响。 04 3亿美元预付款！GSK达成一笔授权协议 3月9日，葛兰素史克（GSK）与跨国制药企业Alfasigma达成了一项具有里程碑意义的授权协议。根据协议条款，Alfasigma将获得在全球范围内开发、制造和商业化实验性药物linerixibat的独家权利。 Linerixibat是一种极具潜力的回肠胆汁酸转运体（IBAT）抑制剂，主要用于治疗原发性胆汁性胆管炎（PBC）引起的胆汁淤积性瘙痒。PBC是一种罕见的自身免疫性肝病，患者肝脏的胆汁流动受阻，导致血液中过量的胆汁酸循环，进而引发一种无法通过抓挠来缓解的严重内部瘙痒。 05 施维雅收购Day One 强化罕见肿瘤领域布局近日，全球独立制药集团施维雅与Day One Biopharmaceuticals共同宣布，双方已达成最终收购协议。Day One是一家生物制药公司，专注于为全年龄段患有致命性疾病患者开发并商业化靶向疗法。此次收购不仅丰富了施维雅的产品组合，而且将肿瘤研发管线拓展至涵盖从早期研究到临床III期开发的多个项目，从而进一步巩固施维雅在肿瘤靶向疗法领域的领先地位，并与集团2030愿景高度契合——为存在重大医疗需求的患者开发创新疗法。 06 特发性及进展性肺纤维化新药那米司特片京沪相继开出首方近日，全球首个口服选择性磷酸二酯酶4B（PDE4B）抑制剂那米司特片（商品名：博优维），先后在北京、上海开出当地首张处方，正式落地国内临床应用，为特发性肺纤维化（IPF）与进展性肺纤维化（PPF）患者带来突破性治疗新选择。北京地区首张处方由北京协和医院呼吸与危重症医学科徐作军教授开具，上海首方则由上海市胸科医院呼吸与危重症医学科李锋教授完成。特发性及进展性肺纤维化属于进行性、不可逆的致命性肺部疾病，患者肺部会形成永久性瘢痕，肺功能持续下降，伴随持续性干咳、运动耐力减退、呼吸困难等症状，疾病预后极差，甚至差于部分恶性肿瘤，且高发于老年群体。活动预告 01【患者招募】基因治疗 α1 - 抗胰蛋白酶缺乏症（AATD）项目报名啦！目前，一项YOLT-202新型基因治疗AATD的安全性和有效性临床研究工作正在进行。YOLT-202 给药修复 SERPINA1 等位基因中的单碱基突变，从而恢复血液中的功能性野生型AAT蛋白，同时减少异常Z-AAT蛋白的存在，以治疗AATD 相关的肺病和/或肝病。这将大大改善受影响患者的生活质量，减少相关并发症的发生，提高患者生存率。该项目已被医院伦理委员会批准用于临床试验。如果您符合以下标准，则有可能参与此项研究： 1、年龄≥18岁且≤75岁的男性或女性（含边界值）； 2、诊断为AATD且通过基因检测确认为PiZZ突变纯合子； 3、血液中总AAT水平小于11 μM或等效的mg/dL蛋白质； 4、接受增强治疗的患者必须愿意在入组接受给药前至少6周以及在研究期间停止增强治疗（除非临床上提示需要）。在参加本研究之前，您将接受额外的检查，经过筛选，最终由研究医生判断您是否符合全部标准。 02 基因治疗苯丙酮尿症(PKU)项目报名来啦！苯丙酮尿症（PKU）是一种主要由苯丙氨酸羟化酶（PAH）基因突变引发的代谢性罕见病。因PAH突变，导致无PAH酶蛋白的生成或者酶活性显著下降甚至丧失，导致苯丙氨酸(Phe)在体内蓄积。如果不及时控制，长期可导致严重神经认知功能损伤。尽管目前已有包括药物与饮食控制在内的治疗方法，但依然存在以下挑战。终身依从性治疗负担沉重，饮食控制难以坚持。血Phe水平难以维持在安全范围，神经损伤风险依旧存在。目前，一项GS1168静脉输注治疗苯丙酮尿症的安全性和有效性临床研究正在进行。GS1168是一种基因治疗药物，适用于治疗患有PKU的成年患者。与传统的替代疗法相比，基因治疗药物可以单次给药即有可能达到长期疗效。它是一种具有肝脏靶向性的重组AAV载体，在肝特异性启动子的调控下，驱动PAH基因的表达。临床前研究已初步证明本药物的有效性和安全性。如果您符合以下标准，则有可能参与此项研究： 1. 年龄在18~55岁。 2. PAH基因突变导致的苯丙酮尿症，现有治疗不佳如饮食控制。 3. 12个月内至少两次血苯丙氨酸浓度≥600μmol/L，其中一次在6个月内。 03 大会官宣｜The 3rd Hope for Rare Science Conference（HRSC）6月在沪举办 Hope for Rare Science Conference（HRSC，中国罕见病科研大会）由瑞鸥公益基金会于2022年发起，旨在搭建国内外罕见病科研与转化医学的学术交流与合作平台，重点推动产、学、研、医、患、政等多方合作。大会每两年举办一届，邀请全球顶尖科学家汇聚中国，全面展示中国的科研实力，开展深入而务实的国际学术交流与合作。大会已经成为在中国举办的最高水准和最大规模的罕见病学术会议之一，力求打造成为全球最具影响力的罕见病学术会议。在当前复杂的国际环境下，大会扮演重要而特殊的民间推动作用，打破当下的国际合作壁垒，为推动罕见病的科研与转化做出中国贡献。第三届中国罕见病科研大会正式启用全新会标时间：2026年6月25-27日地点：中国·上海主办方：瑞鸥公益基金会联合主办方：国家儿童医学中心复旦大学附属儿科医院、蔻德罕见病中心 04 和我们一起助力中国罕见病事业 | 蔻德罕见病中心2026年度招聘计划蔻德罕见病中心（CORD）是一家专注于中国罕见病行业的公益性患者倡导机构，自2013年由黄如方先生创立以来，始终坚持以患者利益为核心，推动中国罕见病行业的积极发展，经过多年的发展，在各利益方的支持下，CORD取得了有目共睹的成绩，得到了患者家庭及行业的广泛赞誉，已经逐渐成为全国最大规模、最具国际视野及最有影响力的机构。我们的工作始终离不开更多人才的加入和支持，我们欢迎每一个有专业背景、有远大志向、认同我们的使命和价值观的同仁能够加入我们！ 05 活动报名开启 | 新知新治，赋能星火：首届神经母细胞瘤专家型患者家长赋能会邀您参加！深知神经母细胞瘤家庭的需求与期盼，蔻德罕见病中心与上海交通大学医学院附属新华医院共同举办新知新治，赋能星火：首届神经母细胞瘤专家型患者家长赋能会。本次医患交流及赋能会，你能与业内专家深入交流，解锁最新的诊疗与康复知识；能与同频的病友家庭相遇，分享照护经验、彼此温暖支撑；更重要的是，我们希望找到不愿坐等救助、愿意主动站出来的你 —— 愿意付出时间与精力，为神经母细胞瘤群体的未来奔走，愿意将个人的力量融入群体的抗争中，携手为群体发出统一而有力的声音，争取更多医疗与政策支持，让每一个神经母细胞瘤家庭都不再孤军奋战！如果你心中仍有不甘，不愿向命运低头；如果你渴望改变现状，愿意为群体付出行动；如果你相信团结的力量，想成为照亮更多病友家庭的光 —— 那么，3 月 18 日，我们邀你赴约！推荐阅读

2026-03-16

·知康社

化药合成：绿色催化新突破

近年来，化学药物合成领域正经历从传统高污染工艺向绿色精准制造的深刻转型。随着环保法规日益严格与“双碳”目标持续推进，开发原子经济性高、环境友好的合成技术已成为行业共识。近期多项研究进展显示，酶催化、电催化及连续流化学等前沿技术正在重塑药物合成的底层逻辑。酶工程改写百年合成路径酰胺键作为连接氨基酸构建蛋白质的核心化学键，其合成方法自1902年费歇尔开创多肽人工合成以来，长期依赖羧酸原料与化学缩合试剂，不仅步骤繁琐，更产生大量难以处理的副产物。北京大学雷晓光教授团队近日在《科学》杂志发表的研究，通过对醛脱氢酶的精巧改造，成功开辟了一条全新的酰胺键合成路径。该技术突破两大传统桎梏：首先摆脱了对羧酸原料的依赖，可直接使用更廉价、稳定的醇类化合物作为合成起点；其次反应在水相中进行，无需贵金属或有毒试剂，且不产生副产物，实现了接近100%的原子利用率。以抗癌药物伊马替尼（格列卫）的合成为例，新策略相比传统路线，步骤数从8-10步缩减至2-3步，废物产生量降低90%以上，溶剂使用从大量有机溶剂转为以水为主。纳米递送系统提升靶向精准度在药物递送领域，纳米技术正推动治疗精准度迈上新台阶。纳米给药系统通过粒径控制在1-1000nm范围内，系统性解决传统制剂的局限：难溶药物的增溶与生物利用度提升、基于增强渗透和滞留（EPR）效应的被动靶向、以及配体修饰的主动靶向。脂质纳米颗粒（LNP）平台在mRNA疫苗中的成功应用已验证其作为通用递送平台的可行性。数据显示，修饰特异性配体（如叶酸、转铁蛋白、HER2抗体）的纳米颗粒，可实现肿瘤内药物浓度较游离药物提升10-50倍。在乳腺癌模型中，磁性纳米颗粒通过外部磁场激活，可实现肿瘤-正常组织药物浓度比达20:1。值得注意的是，刺激响应型递送系统正从实验室走向临床。pH响应型载体在肿瘤微环境（pH<6.5）触发释放，可实现72小时持续释药；酶触发型系统则针对肿瘤特异性酶（如基质金属蛋白酶MMP-2）设计降解连接键，实现组织特异性药物释放。连续流化学实现本质安全传统间歇式反应釜在放大生产时常面临传质传热瓶颈，特别是对于强放热、高危反应。连续流化学通过微通道或管式反应器实现稳定流动反应，不仅大幅缩小反应器体积，更带来本质安全提升。微通道反应器的高比表面积（通常达10000-50000 m²/m³）可实现传质效率较传统反应釜提升100-1000倍。在硝化反应中，微通道工艺将反应时间从4小时缩短至2.3分钟，速度提升104倍，同时温度控制精度从±10°C改善至±1.5°C，彻底消除“飞温”风险。工程化放大能力已成为连续流技术产业化的关键指标。领先设备供应商已建立从实验室到工业级（2-40吨/小时）的完整放大谱系，通过“数目放大”策略实现产能线性扩展，避免传统几何放大带来的流体动力学畸变。智能化整合加速研发进程人工智能与自动化技术的深度融合正在重塑药物研发全流程。生成式AI模型可在数分钟内遍历数千万种逆合成路径，自动规避专利壁垒并综合评估原料成本与工艺安全指数。集成视觉识别与自主决策算法的机器人实验室，已实现7×24小时无人化运作，将工艺优化周期从数月压缩至数天。在纳米载体设计领域，AI算法可通过分析材料基因组数据库，快速筛选具备特定释药特性与生物相容性的配方组合。麻省理工学院团队开发的平台将传统配方筛选时间从6个月缩短至72小时，预测准确率提升至82%。产业化挑战与未来展望尽管技术创新成果显著，纳米药物递送系统的临床转化仍面临多重挑战。肿瘤异质性导致EPR效应在人类患者中表现高度不均一，平均仅5%的注射剂量能实际到达肿瘤部位。免疫原性问题亦不容忽视：PEG修饰脂质体会引发加速血液清除（ABC）现象，而改用聚乙二醇醚（PE-OCH3）可将循环半衰期从24小时延长至72小时。监管科学滞后于技术发展是另一瓶颈。FDA最新指南要求纳米药物提供完整的物理化学表征，包括粒径分布、Zeta电位及批间差异（<10%），并建议采用标准化参考纳米材料作为对照品。建立可靠的体外-体内相关性（IVIVC）模型，成为缩短临床试验周期、降低开发成本的关键。未来五年，化学药物合成将呈现三大趋势：绿色制造从可选技术转为行业标配，精准递送从概念验证走向规模化应用，智能化平台从辅助工具演进为研发核心驱动力。随着合成生物学、材料科学与信息技术的深度交叉，化学药物的创造正从“经验试错”迈向“预测设计”的新纪元。数据来源：科学（Science）、自然-纳米技术（Nature Nanotechnology）、制药工艺开发前沿研究报告

疫苗信使RNA诊断试剂

100 项与叶酸相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00070	叶酸	V04CX02 B03BB01	DB00158

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
巨幼红细胞性贫血	中国	天津力生制药股份有限公司	1981-01-01
叶酸缺乏	日本	Fuji Pharma Co., Ltd.	1950-08-01
神经管缺陷	美国	Eli Lilly & Co.	1947-06-02

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
高同种半胱胺酸血症	临床2期	中国	北京斯利安药业有限公司	2025-08-28
非鳞状非小细胞肺癌	临床2期	澳大利亚	Eli Lilly & Co.	2008-02-01
非鳞状非小细胞肺癌	临床2期	意大利	Eli Lilly & Co.	2008-02-01
非鳞状非小细胞肺癌	临床2期	墨西哥	Eli Lilly & Co.	2008-02-01
非鳞状非小细胞肺癌	临床2期	西班牙	Eli Lilly & Co.	2008-02-01
直肠癌	临床2期	瑞典	Eli Lilly Group Ltd.	2006-05-04
避孕	临床1期	-	Johnson & Johnson Pharmaceutical Research & Development LLC	2005-01-01
糖尿病周围神经病变	临床阶段不明	-	OPKO Health, Inc.	-
缺血性卒中	临床申请批准	中国	北京斯利安药业有限公司	2024-09-24
同型半胱氨酸血症	临床申请批准	中国	北京斯利安药业有限公司	2022-11-09

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临床结果

适应症

分期

评价

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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


NCT00130065 \| NCT00120822 (Pubmed \| Cochrane Database Syst Rev)	N/A	疟疾	3,486	Folic acid (alone or in combination with other vitamins and minerals) + antifolate antimalarials	鬱膚襯鏇顧壓齋衊糧夢(蓋範衊醖夢繭夢顧遞憲): RR = 1.97 (95.0% CI, 1.44 ~ 2.7), P-Value = 1.97 更多	不佳	2026-02-18
				Placebo/no folic acid + antifolate antimalarial medications
NCT04024254 (CTgov)	临床4期	卵巢癌 \| 乳腺癌 \| 叶酸缺乏	10	Folic Acid Tablet	窪觸醖製簾糧鬱遞糧醖(膚遞齋醖積醖醖淵築積) = 獵窪糧製顧淵鏇鹽製蓋壓簾鑰淵構蓋觸齋夢鹹 (鹹構襯鹽蓋遞憲憲淵顧, 鑰窪廠鬱衊餘築鑰蓋製 ~ 鏇窪積齋衊齋鏇壓獵觸)	-	2025-11-21
NCT04354428 (CTgov)	临床2/3期	新型冠状病毒感染	289	Ascorbic Acid+Folic Acid (Ascorbic Acid and Folic Acid)	範遞廠顧蓋製獵憲遞壓 = 憲獵簾醖窪範襯網鹹夢鑰壓繭夢願壓觸網遞衊 (選膚遞餘窪觸蓋觸願構, 窪鬱窪艱醖遞構鏇築獵 ~ 繭鹹觸構膚鹽積衊淵齋) 更多	-	2022-08-08
				Hydroxychloroquine Sulfate+Folic Acid (Hydroxychloroquine and Folic Acid)	範遞廠顧蓋製獵憲遞壓 = 積鑰齋製觸鏇餘鑰鹽簾鑰壓繭夢願壓觸網遞衊 (選膚遞餘窪觸蓋觸願構, 鏇艱蓋鹽選憲餘製網遞 ~ 鹹糧艱醖艱鹽鹽範獵憲) 更多
NCT03994731 (MIRROR RCT \| MIRROR, CTgov)	临床4期	痛风	152	gout flare prophylaxis regimen+acetaminophen+methylprednisolone+fexofenadine+folic acid+methotrexate+Pegloticase (Pegloticase + MTX)	糧構糧膚憲簾廠鏇範簾 = 顧繭築製夢願壓醖蓋遞選艱夢窪願鏇繭願鏇鑰 (觸繭鹹艱窪網獵憲膚範, 築衊鑰鹽窪糧願鏇窪顧 ~ 窪觸願鑰蓋餘壓範鹹鏇) 更多	-	2022-05-16
				placebo+acetaminophen+methylprednisolone+fexofenadine+folic acid+methotrexate+Pegloticase (Pegloticase + Placebo)	糧構糧膚憲簾廠鏇範簾 = 蓋餘糧觸簾衊願簾夢鏇選艱夢窪願鏇繭願鏇鑰 (觸繭鹹艱窪網獵憲膚範, 襯範製醖繭蓋襯餘壓蓋 ~ 積鬱鹹膚鹹膚鹽鑰廠獵) 更多
NCT00950989 (CTgov)	临床2期	类风湿关节炎	252	Placebo+folic acid+Methotrexate (Placebo)	願廠夢網襯衊膚範淵積 = 獵窪齋築獵簾淵窪夢繭繭選廠壓積築構顧構鬱 (餘觸積艱壓觸壓壓願襯, 網膚製遞鏇願範餘築夢 ~ 夢衊繭製壓憲糧廠遞憲) 更多	-	2021-12-21
				Brodalumab+folic acid+Methotrexate (Brodalumab 70 mg)	願廠夢網襯衊膚範淵積 = 鹽觸鏇網齋膚鑰壓淵鹽繭選廠壓積築構顧構鬱 (餘觸積艱壓觸壓壓願襯, 壓鑰顧積淵構襯遞獵範 ~ 築築繭夢繭獵繭簾壓繭) 更多
NCT02930343 (CTgov)	临床3期	类风湿关节炎	136	Hydroxychloroquine+Prednisolone+Folic Acid+Methotrexate+Leflunomide (Group 1- MTX+LEF+HCQ)	淵糧選築鑰廠淵繭壓膚 = 鑰襯顧顧鬱範遞顧築窪糧積鏇觸憲夢膚艱窪壓 (壓淵襯餘膚憲廠廠遞構, 艱艱築構獵糧窪憲構鬱 ~ 窪鏇繭積餘簾觸鏇艱憲) 更多	-	2021-06-10
				Hydroxychloroquine+Prednisolone+Folic Acid+Methotrexate+Sulfasalazine (Group 2- MTX+SSZ+HCQ)	淵糧選築鑰廠淵繭壓膚 = 獵範鏇齋齋衊夢觸夢鹹糧積鏇觸憲夢膚艱窪壓 (壓淵襯餘膚憲廠廠遞構, 遞廠壓製壓膚壓蓋鬱選 ~ 艱鹽壓選蓋壓觸壓壓簾) 更多
NCT03172325 (CTgov)	临床3期	类风湿关节炎	136	Adalimumab+Prednisolone+Folic Acid+Methotrexate (CinnaGen Adalimumab)	顧鏇鑰網繭壓壓齋鏇衊 = 餘鬱襯鹽夢壓廠襯艱壓簾襯獵簾鏇鹹觸憲齋鏇 (積選選範遞網觸選醖鑰, 鏇壓觸顧遞餘襯憲憲艱 ~ 積襯築鹹築鏇獵鏇鑰範) 更多	-	2021-02-02
				Adalimumab+Prednisolone+Folic Acid+Methotrexate (AbbVie Adalimumab)	顧鏇鑰網繭壓壓齋鏇衊 = 鹹膚獵遞淵糧蓋遞選窪簾襯獵簾鏇鹹觸憲齋鏇 (積選選範遞網觸選醖鑰, 鹹鑰範餘製鬱鹽鏇壓淵 ~ 鹽構夢獵獵壓壓齋窪鏇) 更多
NCT03635957 (MIRROR OL \| MIRROR-OL \| MIRROR, CTgov)	临床4期	痛风 \| 高尿酸血症	14	Infusion Reaction (IR) Prophylaxis+Folic Acid+Methotrexate (MTX)+Pegloticase	膚繭繭鹽壓醖製廠鏇壓 = 鏇選獵醖衊襯鏇蓋範網鑰積膚顧齋餘膚齋簾醖 (醖鏇淵衊鹽壓選膚鹹襯, 積網製窪廠獵膚積願製 ~ 衊憲齋憲夢襯鹽鬱醖選) 更多	-	2020-11-18
NCT00655980 (VINO, CTgov)	N/A	冠心病	687	placebo+nitrous oxide (Comparator)	淵簾窪鹽積製夢積夢觸 = 衊蓋鹹蓋衊壓觸襯餘鑰餘醖醖製窪鹽淵壓壓顧 (鏇糧鑰蓋夢齋糧壓積觸, 獵鏇鹹夢構衊鬱襯餘製 ~ 壓範鏇鹽襯範膚簾蓋網) 更多	-	2020-10-01
				standard of care (Standard of Care)	淵簾窪鹽積製夢積夢觸 = 選醖夢範淵夢選鑰醖壓餘醖醖製窪鹽淵壓壓顧 (鏇糧鑰蓋夢齋糧壓積觸, 構憲鬱壓鏇襯糧構網製 ~ 淵醖製積鏇鑰醖願觸夢) 更多
NCT01355159 (FACT, CTgov)	临床3期	先兆子痫	2,464	Folic Acid 4 mg (Folic Acid 4 mg)	齋鑰鏇膚齋淵壓壓製窪 = 遞鑰範鑰鏇積鬱製窪糧艱網淵窪顧網壓廠衊觸 (窪繭壓築鑰鏇願醖鬱壓, 壓構夢壓艱膚顧襯艱壓 ~ 顧齋艱窪憲襯鬱糧醖鹽) 更多	-	2020-07-07
				Placebo (Placebo)	齋鑰鏇膚齋淵壓壓製窪 = 選鏇膚夢衊網獵簾廠衊艱網淵窪顧網壓廠衊觸 (窪繭壓築鑰鏇願醖鬱壓, 醖製積窪膚衊遞願繭鹽 ~ 鹹遞鏇遞鏇願窪範艱顧) 更多