Pridopidine

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。 亨廷顿病是由亨廷素(暂定名) ( HTT )基因的第一个外显子上的CAG重复序列引起的，产生一种症状三联征：运动、认知和行为。虽然患者会出现严重的焦虑和强迫症问题，但运动症状的并发症—吞咽困难和跌倒，通常是导致死亡的原因。 下文介绍了5种值得关注的亨廷顿疗法。 Prilenia Therapeutics 9月，Prilenia Therapeutics宣布，欧洲药品管理局（European Medicines Agency）已接受其pridopidine 的上市许可申请。pridopidine是一种治疗亨廷顿病的“高选择性和强效”的sigma-1受体激动剂。 2023年4月报告的III期PROOF-HD研究结果显示，pridopidine未能达到主要终点和关键次要终点。然而，对数据的进一步分析表明，该候选药物在不服用抗多巴胺能药物和舞蹈症药物的患者中产生了有临床意义的疗效。Sage Therapeutics Sage Therapeutics正在开发dalzanemdor，这是一种潜在的NMDA受体阳性变构调节剂，用于亨廷顿氏症相关的认知障碍。该生物技术公司于今年6月份报告了一项小型II期试验的数据，该试验显示，在第28天，通过hd -认知评估电池综合评分，dalzanemdor和安慰剂之间存在微小的数值差异，该公司还指出，其他预先指定的分析显示出潜在的积极信号。 Sage准备在今年晚些时候报告dalzanemdor治疗亨廷顿舞蹈症的II期DIMENSION研究数据。uniQure 荷兰生物技术公司uniQue正在开发一种名为AMT-130的microRNA基因疗法，这种疗法可以被输送到大脑深处，以抑制突变HTT （mHTT）蛋白的产生。 2024年7月，该公司报告了其AMT - 130Ⅰ/Ⅱ期试验中29例患者的24个月中期数据，显示剂量依赖性减缓疾病进展。 uniQue首席医疗官Walid Abi-Saab表示，我们相信，这是亨廷顿舞蹈病研究药物的第一个临床试验，显示出潜在的长期临床益处和减少神经变性关键标志物的证据。 根据其第三季度财报，AMT-130已被FDA授予孤儿药、快速通道和再生医学先进疗法（Regenerative Medicine Advanced Therapy）的认证，uniQure计划在本月晚些时候与监管机构举行B类会议，讨论加速开发途径的可能性。Wave Life Sciences Wave Life Sciences正在开发首个针对亨廷顿舞蹈症的等位基因特异性沉默疗法WVE-003，它是一种反义寡核苷酸，靶向mHTT mRNA上的核苷酸多态性，同时保持健康的亨廷顿蛋白完整。 2024年6月，Wave报道，在一项Ib/IIa期试验中，候选药物显著且选择性地降低了mHTT蛋白水平。24周后，与安慰剂相比，WVE-003治疗使患者脑脊液中的mHTT水平降低了46%。 虽然该项目最初是与武田制药合作，但这家大型制药公司上个月退出了合作。WVE-003的首席执行官Paul Bolno表示， Wave已经开始与监管机构就临床开发路径进行接触，以支持加速审批。Roche and Ionis 罗氏和Ionis制药公司正在合作开发tominersen，目前在对患有前驱和早期表现的亨廷顿病的患者进行II期临床试验。 在之前的临床试验中，tominersen被证明通过阻断毒性mHTT的产生来降低其水平。反义寡核苷酸通过腰椎穿刺注入脑脊液。 Tominersen的发展历程并非没有挑战。2021年3月，罗氏在非盲独立数据监测委员会预先计划的数据审查后，停止了该候选药物治疗显性亨廷顿病的III期试验。Ionis当时表示，该建议与tominersen对患者的潜在益处/风险有关。 罗氏和lonis正全力布局亨廷顿舞蹈症。除了中期的tominersen试验，罗氏去年还向长期合作伙伴支付了两项针对亨廷顿舞蹈症和阿尔茨海默病的RNA靶向项目的费用。 参考资料： www.biospace.com -END- 2025CMC-CHINA药博会 • 展位火热预定中！

iStock, dani3315 A fatal, highly hereditary illness with no disease-modifying treatments, Huntington’s is long overdue for a therapeutic win. Here, BioSpace looks at five candidates that could change the trajectory for patients. Huntington’s disease has perplexed researchers for decades . Despite being one of the first genetic neurodegenerative illnesses for which science was able to pinpoint the causative gene, modern medicine is still searching for a disease-modifying treatment for this formidable foe. “Here we are, decades later, and we still don’t know what to do with that information to prevent people from having decline from all the different functions of the brain and ultimately dying from the illness,” David Shprecher, movement disorder director at Banner Sun Health Research Institute, told BioSpace . Huntington’s, which is caused by a CAG repeat in the first exon of the huntingtin ( HTT ) gene, generates a triad of symptoms: motor, cognitive and behavioral. While patients can develop severe issues with anxiety and obsessive-compulsive disorder, it is complications from the motor symptoms—including difficulty swallowing and falls—that are usually the cause of death, according to Shprecher. “The problem is we don’t fully understand why the gene mutation causes damage to the brain,” he said. Clinical trials are another challenge, he continued, with only about 41,000 symptomatic patients in the U.S. and many not at a stage where they’re eligible to participate. Geographic barriers are also significant as most trials are conducted at major academic centers and require in-person assessments. “There’s been a real push to use a lot more telehealth and biometric remote technology” to allow more access to these important trials, Shprecher said. While the Huntington’s community has experienced multiple letdowns over the last four years, biopharma is not giving up. Several companies, including Prilenia Therapeutics, uniQure and Sage Therapeutics are hopeful that their approaches can make a tangible difference for patients. Here, BioSpace reviews five investigational drugs that could change the trajectory for patients with Huntington’s disease. Prilenia Therapeutics Pridopidine Prilenia Therapeutics announced in September that the European Medicines Agency has accepted its Marketing Authorisation Application for pridopidine, a “highly selective and potent” agonist of the sigma-1 receptor. Topline results reported in April 2023 from the Phase III PROOF-HD study revealed a miss for pridopidine, which failed to meet the primary and key secondary endpoints. However, further analysis of the data showed that the candidate elicited clinically meaningful efficacy in patients not taking anti-dopaminergic and chorea medications. The Huntington’s community had been hopeful of pridopidine’s potential to treat Parkinsonian symptoms experienced by patients, Shprecher said, as these are not addressed by any current treatments. However, he added, “there would be very few Huntington’s disease patients eligible for a trial if it excludes both of those types of medications.” Sage Therapeutics Dalzanemdor Sage Therapeutics is developing dalzanemdor, a potentially first-in-class positive allosteric modulator of the NMDA receptor, for cognitive impairment associated with Huntington’s. The Cambridge, Mass.–based biotech reported data in June from a small, Phase II trial in which there was a “small numerical difference” between dalzanemdor and the placebo as measured by the HD-Cognitive Assessment Battery composite score on day 28, with the company also noting that other “prespecified analyses” showed potential positive signals. Huntington’s watchers, however, were not impressed. In a note to investors at the time, William Blair analysts called the results “underwhelming” and said they “remain cautious” on dalzanemdor and “do not view the small numerical changes as definitive” based on the results of this study. Sage is gearing up to report data from the Phase II DIMENSION study of dalzanemdor in Huntington’s later this year, a win it needs after the drug failed to show efficacy in Alzheimer’s and Parkinson’s . uniQure AMT-130 Dutch biotech uniQure is developing a microRNA gene therapy, AMT-130, which is delivered deep inside the brain to inhibit the production of the mutant HTT (mHTT) protein. In July 2024, the company reported 24-month interim data from its Phase I/II trial of AMT-130 in 29 patients showing a dose-dependent slowing of disease progression. “We believe this is the first clinical trial of any investigational medicine for Huntington’s disease to show evidence of a potential long-term clinical benefit and reduction of a key marker of neurodegeneration,” Walid Abi-Saab, chief medical officer of uniQure, said in the press release at the time. AMT-130 has been granted orphan drug, Fast Track and Regenerative Medicine Advanced Therapy designations from the FDA, and uniQure has scheduled a Type B meeting with the regulator for later this month to discuss the potential for an accelerated development pathway, according to its Q3 earnings report . Wave Life Sciences WVE-003 Wave Life Sciences is developing the first allele-specific silencing therapy for Huntington’s. An antisense oligonucleotide, WVE-003 targets a nucleotide polymorphism present on the mHTT mRNA while leaving healthy huntingtin intact. In June 2024, Wave reported that the candidate significantly and selectively reduced levels of the mHTT protein in a Phase Ib/IIa trial. After 24 weeks, treatment with WVE-003 led to a 46% drop in mHTT levels in patients’ cerebrospinal fluid versus placebo. While the program was initially partnered with Takeda, the larger pharma stepped back from the collaboration last month. Now taking WVE-003 forward itself, CEO Paul Bolno told BioSpace that Wave has “initiated engagement” with regulators regarding a clinical development path that could support accelerated approval. Roche and Ionis Tominersen Roche and Ionis Pharmaceuticals are partnered on the development of tominersen, which is currently being studied in a Phase II clinical trial of patients with prodromal and early manifest Huntington’s disease. In previous clinical trials , tominersen was shown to lower levels of toxic mHTT by blocking its production. The antisense oligonucleotide is administered through a lumbar puncture into the cerebrospinal fluid. Tominersen’s development journey has not been without challenges. In March 2021, Roche discontinued a Phase III trial of the candidate in manifest Huntington’s disease after a pre-planned data review by an unblinded Independent Data Monitoring Committee. The recommendation was related to tominersen’s potential benefit/risk pro patients, Ionis said at the time. Roche and Ionis are going all in on Huntington’s. In addition to the mid-stage tominersen trial, Roche paid its longtime partner last year for two RNA-targeting programs targeting Huntington’s and Alzheimer’s disease.