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TauRx today announced results from a confirmatory study evaluating hydromethylthionine mesylate in participants with mild cognitive impairment and mild to moderate dementia due to Alzheimer’s disease have been published in The Journal of Prevention of Alzheimer's Disease.
The study supports an earlier publication reporting that hydromethylthionine mesylate (HMTM) halted progression of neurodegeneration in Alzheimer’s disease (AD) and that participants with Mild Cognitive Impairment (MCI) who received HMTM 16 mg/day experienced statistically significant cognitive improvement over 18 months. Participants also displayed no evidence of statistically significant cognitive or functional decline over a period of two years.
The newly-reported study compared closely matched external placebo data to show statistically significant treatment effects. The external placebo data were necessary because the control arm for HMTM in the original clinical trial (protocol TRx-237-039) used to maintain blinding with respect to slight urinary colouration by HMTM had some activity and so was not a true placebo.
The latest study compared data from participants who received HMTM 16 mg/day in the original trial with data from matched placebo controls from the FDA-sponsored Critical Path for AD (CPAD) database meeting key inclusion/exclusion criteria (protocol TRx-237-080) as well as with other control populations.
The new paper, titled Assessment of clinical and neuroimaging efficacy of treatment targeting tau pathology in mild cognitive impairment and mild to moderate Alzheimer’s disease with hydromethylthionine mesylate using external control data, reports statistically significant differences relative to three different external control populations. Key analyses suggest that unmeasured confounding is highly unlikely to explain the observed results.
Prof Bjoern Schelter, TauRx’s Chief Analytics Officer, who is lead author of the newly-published paper, said: “The latest results strongly support the effectiveness of HMTM in people living with MCI and mild to moderate dementia due to AD."
“By comparing participants receiving HMTM 16 mg/day with external control populations, we have been able to navigate the blinding problem and so demonstrate consistent and clinically meaningful differences in cognitive decline (ADAS-Cog13) and rate of loss of brain volume at 78 and 104 weeks, as well as a global measure of progression of dementia (CDR-SB) over 104 weeks."
“The latest results are consistent with our earlier report demonstrating that HMTM could have significant treatment effects on neurodegeneration, tau pathology and brain atrophy. The totality of the evidence now available reinforces our belief that HMTM has the potential to offer an accessible oral treatment option which could be delivered safely and with minimal patient/physician burden.”
The original TRx-237-039 (LUCIDITY) trial confirmed HMTM has a benign safety profile, with headache (1.5%) and diarrhoea (1.2%) reported as the most frequent adverse effects at the 16 mg/day dose.
HMTM is an investigational drug and a Marketing Authorisation Application from TauRx Therapeutics Management Ltd is currently being evaluated by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).
《阿尔茨海默病预防杂志》发表TauRx公司关于潜在口服疗法疗效的验证性研究结果
TauRx公司今日宣布，一项评估氢甲基硫氨酸甲磺酸盐用于轻度认知障碍及轻中度阿尔茨海默病所致痴呆受试者的验证性研究结果已发表于《阿尔茨海默病预防杂志》。
该研究支持早前发表的一项报告，该报告指出氢甲基硫氨酸甲磺酸盐（HMTM）可阻止阿尔茨海默病（AD）的神经退行性进展，且接受HMTM 16 mg/天治疗的轻度认知障碍（MCI）受试者在18个月内表现出统计学上显著的认知改善。受试者在两年期间亦未显示出具有统计学意义的认知或功能衰退证据。
这项新发布的研究通过对比严格匹配的外部安慰剂数据，展示了统计学上显著的治疗效果。采用外部安慰剂数据是必要的，因为在原始临床试验（方案编号 TRx-237-039）中，用于维持HMTM所致尿液颜色盲法的对照组具有一定的活性，因此并非真正的安慰剂。
最新研究对比了原始试验中接受HMTM 16 mg/天治疗的受试者数据，与来自FDA资助的"阿尔茨海默病关键路径"（CPAD）数据库中符合关键入排标准（方案编号 TRx-237-080）的匹配安慰剂对照数据，以及其他对照人群的数据。
这篇题为“使用外部对照数据评估氢甲基硫氨酸甲磺酸盐靶向tau蛋白病理治疗轻度认知障碍及轻中度阿尔茨海默病的临床与神经影像疗效”1 的新论文报告了与三个不同外部对照人群相比具有统计学显著差异的结果。关键分析表明，未测量的混杂因素极不可能导致所观察到的结果。
TauRx公司首席分析官、该新发表论文的第一作者Bjoern Schelter教授表示：“最新结果有力支持了HMTM对MCI及轻中度AD所致痴呆患者的有效性。”
“通过将接受HMTM 16 mg/天治疗的受试者与外部对照人群进行比较，我们得以克服盲法问题，从而在78周和104周时，在认知功能下降（ADAS-Cog13）和脑容积流失率方面，以及在神经影像学指标方面，均观察到了显著的积极结果。”
“最新结果与我们早前报告一致，表明HMTM可能对神经退行性变、tau蛋白病理及脑萎缩具有显著的治疗效果。目前获得的全部证据进一步强化了我们的信念，即HMTM有潜力成为一种易于获取的口服治疗选择，能够安全给药，且对患者/医生的负担极小。”
原始TRx-237-039（LUCIDITY）试验证实HMTM具有良好的安全性特征2,3，在16 mg/天剂量下，报告的最常见不良反应为头痛（1.5%）和腹泻（1.2%）。
HMTM是一种在研药物，TauRx Therapeutics Management Ltd 公司的上市许可申请目前正在接受英国药品与健康产品管理局（MHRA）的审评。
