近日，FDA批准ONPATTRO™（patisiran）脂质复合物注射，是一种首创的RNA干扰（RNAi）治疗药物，用于治疗成人遗传性转甲状腺素介导的（hATTR）淀粉样变性多发性神经病。
批准日期：2018年8月11日 公司：Alnylam制药
ONPATTRO（patisiran）脂质复合物注射液，用于静脉注射
美国最初批准：2018年
作用机制
Patisiran是一种双链siRNA，通过RNA引起突变体和野生型TTR mRNA的降解干扰，导致组织中血清TTR蛋白和TTR蛋白沉积物的减少。
适应症和用法
ONPATTRO含有转甲状腺素蛋白导向的小干扰RNA，适用于治疗成人遗传性去甲肾上腺素介导的淀粉样变性多发性神经病。
剂量和给药
•对于体重小于100 kg的患者，建议剂量为静脉输注每3周0.3mg/kg。对于重量为100kg或以上的患者，推荐剂量为30mg
•使用皮质类固醇，对乙酰氨基酚和抗组胺药进行预防。
•在给药前过滤并稀释。
•注入约80分钟。
剂量形式和强度
脂质复合物注射：单剂量小瓶中的10mg/5mL（2mg/mL）。
禁忌症
没有
警告和注意事项
•输液相关反应：监测输液时的体征和症状。如果临床指示，请缓慢或中断输液。如果发生严重或危及生命的输注相关反应，则停止输注。
•血清维生素A水平降低，建议补充：建议每日服用维生素A补充剂。如果出现维生素A缺乏的症状，请咨询眼科医生
不良反应
最常报告的不良反应（发生在ONPATTRO治疗患者的至少10％，并且比安慰剂更频繁地至少3％）是上呼吸道感染和输注相关反应。
要报告疑似不良反应，请致电1-877-256-9526联系Alnylam Pharmaceuticals，或致电1-800FDA-1088联系FDA或www.fda.gov/medwatch。
如何提供/存储和处理
如何提供
ONPATTRO是一种无菌，无防腐剂，白色至灰白色，乳白色，均匀的溶液，用于在单剂量玻璃小瓶中以10mg/5mL（2mg/mL）溶液的形式提供静脉内输注。小瓶塞不是用天然橡胶胶制成的。 ONPATTRO有纸盒装，每个装有一个单剂量的小瓶。
NDC是：71336-1000-1。
存储和处理
储存在2°C至8°C（36°F至46°F）。 不要冻结。 如果小瓶已冻结，请将其丢弃。
如果没有冷藏，ONPATTRO可以在室温最高25°C（最高77°F）下储存长达14天。
有关ONPATTRO在输液袋中稀释后的储存条件，请参阅剂量和给药。
原处方资料附件：https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210922s000lbl.pdf
Alnylam Announces First-Ever FDA Approval of an RNAi Therapeutic, ONPATTRO™ (patisiran) for the Treatment of the Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis in Adults
FDAapproved ONPATTRO™ (patisiran) lipid complex injection, a first-of-its-kind RNA interference (RNAi) therapeutic, for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults.
ONPATTRO is the first and only FDA-approved treatment for this indication. hATTR amyloidosis is a rare, inherited, rapidly progressive and life-threatening disease with a constellation of manifestations. In addition to polyneuropathy, hATTR amyloidosis can lead to other significant disabilities including decreased ambulation with the loss of the ability to walk unaided, a reduced quality of life, and a decline in cardiac functioning. In the largest controlled study of hATTR amyloidosis, ONPATTRO was shown to improve polyneuropathy – with reversal of neuropathy impairment in a majority of patients – and to improve a composite quality of life measure, reduce autonomic symptoms, and improve activities of daily living.
The FDA approval of ONPATTRO was based on positive results from the randomized, double-blind, placebo-controlled, global Phase 3 APOLLO study, the largest-ever study in hATTR amyloidosis patients with polyneuropathy.
In APOLLO, the safety and efficacy of ONPATTRO were eva luated in a diverse, global population of hATTR amyloidosis patients in 19 countries, with a total of 39 TTR mutations. Patients were randomized in a 2:1 ratio to receive intravenous ONPATTRO (0.3 mg per kg of body weight) or placebo once every 3 weeks for 18 months.
The study showed that ONPATTRO improved measures of polyneuropathy, quality of life, activities of daily living, ambulation, nutritional status and autonomic symptoms relative to placebo in adult patients with hATTR amyloidosis with polyneuropathy. The primary endpoint of the APOLLO study was the modified Neuropathy Impairment Score +7 (mNIS+7), which assesses motor strength, reflexes, sensation, nerve conduction and postural blood pressure.
Patients treated with ONPATTRO had a mean 6.0-point decrease (improvement) in mNIS+7 score from baseline compared to a mean 28.0-point increase (worsening) for patients in the placebo group, resulting in a mean 34.0-point difference relative to placebo, after 18 months of treatment.
While nearly all ONPATTRO-treated patients experienced a treatment benefit relative to placebo, 56 percent of ONPATTRO-treated patients at 18 months of treatment experienced reversal of neuropathy impairment (as assessed by mNIS+7 score) relative to their own baseline, compared to four percent of patients who received placebo.
Patients treated with ONPATTRO had a mean 6.7-point decrease (improvement) in Norfolk Quality of Life Diabetic Neuropathy (QoL-DN) score from baseline compared to a mean 14.4-point increase (worsening) for patients in the placebo group, resulting in a mean 21.1-point difference relative to placebo, after 18 months of treatment.
As measured by Norfolk QoL-DN, 51 percent of patients treated with ONPATTRO experienced improvement in quality of life at 18 months relative to their own baseline, compared to 10 percent of the placebo-treated patients.
Over 18 months of treatment, patients treated with ONPATTRO experienced significant benefit vs. placebo for all other secondary efficacy endpoints, including measures of activities of daily living, walking ability, nutritional status, and autonomic symptoms.
The most common adverse events that occurred more frequently with ONPATTRO than with placebo were upper respiratory tract infections and infusion-related reactions. To reduce the risk of infusion-related reactions, patients received premedications prior to infusion.
“FDA approval of ONPATTRO represents an entirely new approach to treating patients with polyneuropathy in hATTR amyloidosis and shows promise as a new era in patient care,” said John Berk, M.D., Associate Professor of Medicine at Boston University School of Medicine and assistant director of the Amyloidosis Center at Boston University School of Medicine. “Given the strength of the APOLLO data, including data showing the possibility of halting or improving disease progression in many patients, ONPATTRO holds tremendous promise for people living with this disease.”