Abstract：
OBJECTIVE: To examine the efficacy and safety of patisiran, an RNA interference therapeutic, in patients from Taiwan with hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy.
METHODS: The APOLLO phase 3 trial included patients from Taiwan who received patisiran 0.3 mg/kg intravenously or placebo once every 3 weeks (q3w) for 18 months (18 M), followed by patisiran 0.3 mg/kg q3w in an ongoing global open-label extension (OLE) study. The primary endpoint was change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 18 M.
RESULTS: Eighteen Taiwanese patients were enrolled in APOLLO (patisiran, n = 8; placebo, n = 10; all A97S gene variant) and 14 continued in the global OLE. In this Taiwanese sub-population, beneficial treatment effects at 18 M were observed in mNIS+7 (least squares mean difference in change from baseline [patisiran-placebo], -26.5 points; 95% confidence interval: -45.5, -7.5). Patients who switched from placebo to patisiran demonstrated slowing of polyneuropathy progression at month 12 in the global OLE, while those who received patisiran in APOLLO maintained the beneficial treatment effects. Patisiran had an acceptable safety profile in the Taiwanese sub-population.
CONCLUSIONS: This analysis suggests that patisiran is well tolerated and may provide a substantial clinical benefit for Taiwanese patients with hATTR amyloidosis with polyneuropathy.
UNASSIGNED: The studies were registered on the ClinicalTrials.gov. The APOLLO study ClinicalTrials.gov identifier is NCT01960348 (https://clinicaltrials.gov/ct2/show/NCT01960348), with the registration date of October 10, 2013, and the first patient was enrolled on December 13, 2013. For the global OLE, the ClinicalTrials.gov identifier is NCT02510261 (https://clinicaltrials.gov/ct2/show/NCT02510261) with the registration date of July 29, 2015, and the first patient was enrolled on July 13, 2015.
METHODS: This study provides Class II evidence that treatment with patisiran is safe and efficacious in Taiwanese patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy.
METHODS: The APOLLO phase 3 trial included patients from Taiwan who received patisiran 0.3 mg/kg intravenously or placebo once every 3 weeks (q3w) for 18 months (18 M), followed by patisiran 0.3 mg/kg q3w in an ongoing global open-label extension (OLE) study. The primary endpoint was change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 18 M.
RESULTS: Eighteen Taiwanese patients were enrolled in APOLLO (patisiran, n = 8; placebo, n = 10; all A97S gene variant) and 14 continued in the global OLE. In this Taiwanese sub-population, beneficial treatment effects at 18 M were observed in mNIS+7 (least squares mean difference in change from baseline [patisiran-placebo], -26.5 points; 95% confidence interval: -45.5, -7.5). Patients who switched from placebo to patisiran demonstrated slowing of polyneuropathy progression at month 12 in the global OLE, while those who received patisiran in APOLLO maintained the beneficial treatment effects. Patisiran had an acceptable safety profile in the Taiwanese sub-population.
CONCLUSIONS: This analysis suggests that patisiran is well tolerated and may provide a substantial clinical benefit for Taiwanese patients with hATTR amyloidosis with polyneuropathy.
UNASSIGNED: The studies were registered on the ClinicalTrials.gov. The APOLLO study ClinicalTrials.gov identifier is NCT01960348 (https://clinicaltrials.gov/ct2/show/NCT01960348), with the registration date of October 10, 2013, and the first patient was enrolled on December 13, 2013. For the global OLE, the ClinicalTrials.gov identifier is NCT02510261 (https://clinicaltrials.gov/ct2/show/NCT02510261) with the registration date of July 29, 2015, and the first patient was enrolled on July 13, 2015.
METHODS: This study provides Class II evidence that treatment with patisiran is safe and efficacious in Taiwanese patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy.
摘要：
目的：为了检查patisiran的疗效和安全性，RNA干扰治疗剂，在台湾遗传性甲状腺素运载蛋白介导的（hATTR）淀粉样变性伴多发性神经病的患者中。
方法：APOLLO3期试验包括来自台湾的患者，这些患者每3周（q3w）静脉注射0.3mg/kg或安慰剂，持续18个月（18M），在一项正在进行的全球开放标签扩展（OLE）研究中，patisiran0.3mg/kgq3w。主要终点是18μM时改良神经病变损伤评分+7(mNIS+7)的基线变化。
结果：APOLLO纳入了18名台湾患者（patisiran，n=8；安慰剂，n=10；全部A97S基因变异体）和14在全局OLE中持续存在。在这个台湾亚人群中,在mNIS+7中观察到18M时的有益治疗效果（与基线[patisiran-安慰剂]变化的最小二乘平均差），-26.5点；95%置信区间：-45.5，-7.5）。在全球OLE中，从安慰剂转为patisiran的患者在12个月时表现出多发性神经病进展缓慢，而在APOLLO接受patisiran的患者保持了有益的治疗效果。Patisiran在台湾亚人群中具有可接受的安全性。
结论：该分析表明，patisiran具有良好的耐受性，并且可能为患有hATTR淀粉样变性多发性神经病的台湾患者提供实质性的临床益处。
■这些研究已在ClinicalTrials.gov上注册。APOLLO研究ClinicalTrials.gov标识符为NCT01960348(https://clinicaltrials.gov/ct2/show/NCT01960348)，登记日期为2013年10月10日,首例患者于2013年12月13日入组.对于全局OLE，ClinicalTrials.gov标识符为NCT02510261(https://clinicaltrials.gov/ct2/show/NCT02510261),注册日期为2015年7月29日,首例患者于2015年7月13日入组.
方法：这项研究提供了II类证据，证明在台湾遗传性转甲状腺素蛋白介导的淀粉样变性多发性神经病患者中，patisiran治疗是安全有效的。
方法：APOLLO3期试验包括来自台湾的患者，这些患者每3周（q3w）静脉注射0.3mg/kg或安慰剂，持续18个月（18M），在一项正在进行的全球开放标签扩展（OLE）研究中，patisiran0.3mg/kgq3w。主要终点是18μM时改良神经病变损伤评分+7(mNIS+7)的基线变化。
结果：APOLLO纳入了18名台湾患者（patisiran，n=8；安慰剂，n=10；全部A97S基因变异体）和14在全局OLE中持续存在。在这个台湾亚人群中,在mNIS+7中观察到18M时的有益治疗效果（与基线[patisiran-安慰剂]变化的最小二乘平均差），-26.5点；95%置信区间：-45.5，-7.5）。在全球OLE中，从安慰剂转为patisiran的患者在12个月时表现出多发性神经病进展缓慢，而在APOLLO接受patisiran的患者保持了有益的治疗效果。Patisiran在台湾亚人群中具有可接受的安全性。
结论：该分析表明，patisiran具有良好的耐受性，并且可能为患有hATTR淀粉样变性多发性神经病的台湾患者提供实质性的临床益处。
■这些研究已在ClinicalTrials.gov上注册。APOLLO研究ClinicalTrials.gov标识符为NCT01960348(https://clinicaltrials.gov/ct2/show/NCT01960348)，登记日期为2013年10月10日,首例患者于2013年12月13日入组.对于全局OLE，ClinicalTrials.gov标识符为NCT02510261(https://clinicaltrials.gov/ct2/show/NCT02510261),注册日期为2015年7月29日,首例患者于2015年7月13日入组.
方法：这项研究提供了II类证据，证明在台湾遗传性转甲状腺素蛋白介导的淀粉样变性多发性神经病患者中，patisiran治疗是安全有效的。
