UCB, a global biopharmaceutical company, today announced that Neurology has published results from a multicenter retrospective chart review study of investigational pyrimidine nucleoside and/or nucleotide therapy in people living with thymidine kinase 2 deficiency (TK2d). The results indicated that pyrimidine nucleoside and/or nucleotide therapy may reduce risk of death and can impact functional outcomes in patients with TK2d..

优时比（UCB），一家全球生物制药公司，今天宣布《神经学》杂志发表了关于嘧啶核苷和/或核苷酸治疗胸苷激酶2缺乏症（TK2d）患者的多中心回顾性图表审查研究结果。结果显示，嘧啶核苷和/或核苷酸治疗可能降低死亡风险，并对TK2d患者的功能结局产生影响。

TK2d is an ultra-rare, life-threatening, genetic mitochondrial disease characterized by progressive and severe muscle weakness (myopathy), which can impact the ability to walk, eat, and breathe independently.

TK2d 是一种超罕见、危及生命的遗传性线粒体疾病，其特征是进行性和严重的肌肉无力（肌病），可能影响独立行走、进食和呼吸的能力。

Key findings of the

主要发现

Neurology

神经病学

publication include:

出版物包括：

No deaths among treated patients (0/38), compared to 58% mortality in untreated patients (40/69).

治疗患者中无死亡病例（0/38），而未治疗患者的死亡率为58%（40/69）。

Estimated reductions in risk of death with treatment were between 85% and 93% (HR 0.067–0.147) for time from TK2d symptom onset and between 75% and 91% (HR 0.091–0.251) for time from treatment start. Treated patients showed a 95% reduction in risk of death by exact conditional logistic regression analysis..

估计通过治疗，从TK2d症状出现开始计算的死亡风险降低幅度为85%至93%（HR 0.067–0.147），而从治疗开始计算的风险降低幅度为75%至91%（HR 0.091–0.251）。经精确条件逻辑回归分析显示，接受治疗的患者死亡风险降低了95%。

Before treatment, around 71% (27/38) of patients lost ≥1 motor milestone and 29% (11/38) of patients lost ≥4 motor milestones. During treatment, no patients lost motor milestones, and after starting treatment, of those who had lost motor milestones, 65% (17/26) regained at least one motor milestone..

治疗前，约 71% (27/38) 的患者失去了 ≥1 个运动里程碑，29% (11/38) 的患者失去了 ≥4 个运动里程碑。在治疗期间，没有患者失去运动里程碑，并且在开始治疗后，在那些失去运动里程碑的患者中，65% (17/26) 恢复了至少一个运动里程碑。

Over 50% (19/38) of the patients were using ventilatory support before treatment. Among those who received treatment, 29% (6/21) experienced a reduction in their need for ventilatory support.

超过50%（19/38）的患者在治疗前使用了呼吸支持。在接受治疗的患者中，29%（6/21）的呼吸支持需求有所减少。

Safety information:

安全信息：

Most treatment-emergent adverse events (TEAEs) were mild and did not lead to discontinuation.1 The most common TEAEs were diarrhea (overall 26/38, 68% those treated with age of symptom onset of ≤12 years, 18/29, 62%), increased blood creatine kinase (CK; overall, 9/38, 23%; those treated with age of symptom onset of ≤12 years, 8/29, 28%), pyrexia (overall, 6/38, 16%; those treated with age of symptom onset of ≤12 years, 6/29, 21%), increased alanine aminotransferase (ALT; overall, 6/38, 16%; those treated with age of symptom onset of ≤12 years, 5/29, 17%), and increased aspartate aminotransferase (AST; overall, 5/38, 13%; those treated with age of symptom onset of ≤12 years, 4/29, 14%)..

大多数治疗中出现的不良事件（TEAEs）为轻度，且并未导致治疗中断。最常见的TEAEs包括腹泻（总体38例中有26例，占68%；发病年龄≤12岁的治疗者中29例中有18例，占62%）、血液肌酸激酶（CK）升高（总体38例中有9例，占23%；发病年龄≤12岁的治疗者中29例中有8例，占28%）、发热（总体38例中有6例，占16%；发病年龄≤12岁的治疗者中29例中有6例，占21%）、丙氨酸氨基转移酶（ALT）升高（总体38例中有6例，占16%；发病年龄≤12岁的治疗者中29例中有5例，占17%）以及天冬氨酸氨基转移酶（AST）升高（总体38例中有5例，占13%；发病年龄≤12岁的治疗者中29例中有4例，占14%）。

Study limitations:

研究局限性：

The study's limitations included potential selection bias due to differing eligibility criteria (mitigated, in part, by a patient matching algorithm), large confidence intervals from no deaths in the treated group complicating result precision, low patient numbers due to the rarity of the condition, and challenges in comparing treated and untreated groups due to variability in data collection and assessment protocols, as well as missing additional data on patient health metrics..

该研究的局限性包括：由于资格标准不同可能导致的选择偏倚（部分通过患者匹配算法减轻）、治疗组无死亡事件导致置信区间较大从而影响结果精确性、因疾病罕见导致患者数量较少，以及由于数据收集和评估协议的差异及患者健康指标数据缺失，比较治疗组与未治疗组存在困难。

'Publication of these results in

‘这些结果的公布

Neurology

神经病学

, a leading medical journal, underscores the significance of these data for the TK2d community,' said Cristina Domínguez-González, Neurology Specialist, University Hospital 12 de Octubre, Madrid, and lead author. 'Our study showed positive results, with pyrimidine nucleoside and/or nucleotide therapy demonstrating improvement in survival.

《一份领先的医学杂志》强调了这些数据对TK2d社区的重要性，”马德里10月12日大学医院神经科专家、主要作者克里斯蒂娜·多明格斯-冈萨雷斯说道。“我们的研究显示了积极的结果，嘧啶核苷和/或核苷酸治疗显示出在生存率上的改善。”

These findings highlight the potential of pyrimidine nucleoside and/or nucleotide therapy as a clinically important therapeutic option, offering hope for a new standard of care if approved by the regulatory authorities.'.

这些研究结果突显了嘧啶核苷和/或核苷酸疗法作为临床上重要治疗选择的潜力，如果获得监管机构批准，将为新的护理标准带来希望。

“TK2 deficiency is an ultra-rare, progressive mitochondrial disorder with no approved therapies or internationally recognized clinical guidelines, leaving patients and families with only supportive disease management,” said Donatello Crocetta, Chief Medical Officer at UCB. “As part of our mission to address severe, underserved diseases, the publication of these findings marks an important milestone — reinforcing our commitment to advancing science into potential first-in-class medicines for this community.”.

“TK2缺乏症是一种超罕见的、进展性的线粒体疾病，目前尚无获批的疗法或国际公认临床指南，患者及其家属只能依靠支持性治疗来管理病情，”UCB首席医学官唐纳泰罗·克罗切塔表示。“作为我们解决严重且未满足需求疾病使命的一部分，这些研究结果的发表标志着一个重要里程碑——进一步印证了我们致力于推进科学，为这一群体开发潜在的首创药物的承诺。”

About thymidine kinase 2 deficiency (TK2d)

关于胸苷激酶2缺乏症（TK2d）

Mitochondrial diseases, like TK2d, affect energy-demanding parts of the body such as muscles, heart, and brain.

线粒体疾病（如TK2d）会影响身体中需要能量的部分，例如肌肉、心脏和大脑。

TK2d is generally categorized as: age of symptom onset ≤12 years and >12 years.3,4,5 TK2d presents with varying severity depending on the age of onset, with cases in the population with age of symptom onset ≤12 years typically being the most rapidly progressing  and cases in the population with age of symptom onset >12 years slower progressing..

TK2d 一般分为：症状发作年龄 ≤12 岁和 >12 岁。3,4,5 TK2d 的严重程度因发病年龄而异，症状发作年龄 ≤12 岁的人群病例通常进展最快，而症状发作年龄 >12 岁的人群病例进展较慢。

The estimated worldwide prevalence of TK2d is 1.64 [0.5, 3.1] cases per 1,000,000 people.

TK2d的全球患病率估计为每百万人1.64例 [0.5, 3.1]。

TK2d profoundly affects multiple health, physical, quality-of-life, and psychosocial domains, as children struggle to achieve developmental milestones or lose them, and adults lose functional independence with challenges in breathing, eating, and walking.

TK2d深刻影响多个健康、身体、生活质量和心理社会领域，因为儿童在努力实现发育里程碑或失去它们，而成人则失去功能独立性，在呼吸、进食和行走方面面临挑战。

About doxecitine and doxribtimine

关于多西环素和强力霉素

Administration of doxecitine and doxribtimine is intended to incorporate the pyrimidine nucleosides, deoxycytidine and deoxythymidine, into skeletal muscle mitochondrial deoxyribonucleic acid (DNA). This action restores mitochondrial DNA copy number in TK2d mutant mice, as suggested by preclinical data..

给药多西西丁和多西溴丁旨在将嘧啶核苷脱氧胞苷和脱氧胸苷整合到骨骼肌线粒体脱氧核糖核酸（DNA）中。根据临床前数据，此作用可恢复TK2d突变小鼠的线粒体DNA拷贝数。

The safety and efficacy of doxecitine and doxribtimine combination therapy has not been established and is not currently approved for use by any regulatory authority worldwide. It is currently under regulatory review by US and EU regulatory authorities.

多西替尼和多西布汀联合疗法的安全性和有效性尚未确定，目前全球任何监管机构均未批准其使用。该疗法目前正在接受美国和欧盟监管机构的审查。

About UCB

关于UCB

UCB, Brussels, Belgium (www.ucb.com), is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With more than 9000 people in approximately 40 countries, the company generated revenue of € 6.1 billion in 2024.

优时比公司（UCB），位于比利时布鲁塞尔（www.ucb.com），是一家全球生物制药公司，专注于发现和开发创新药物与解决方案，以改变免疫系统或中枢神经系统严重疾病患者的生活。公司在约40个国家拥有9000多名员工，并在2024年实现了61亿欧元的收入。