近日，美国食品药品监督管理局(FDA)批准了一种新的基因治疗药物Luxturna，用于治疗儿童和成人患者，这些患者患有可能会导致失明的遗传性视力丧失。Luxturna是美国批准的第一个直接给药的基因疗法，靶向由特定基因突变引起的疾病。
批准日期：2017年12月19日 公司：Spark Therapeutics
LUXTURNA（voretigene neparvovec-rzyl）用于视网膜下注射的眼内悬液
美国最初批准：2017年
作用机制
LUXTURNA设计用于将编码人视网膜色素上皮65kDa蛋白（RPE65）的基因的正常拷贝递送至生物活性RPE65水平降低或缺失的人的视网膜细胞。 RPE65在视网膜色素上皮（RPE）细胞中产生并且将全反式视黄醇转化为11-顺式-视黄醇，其随后在视觉（类视黄醇）循环期间形成视网膜11-顺式-视黄醛。 视觉循环在光转导中是关键的，光转导是指光子在视网膜中的生物转换成电信号。RPE65基因中的突变导致RPE65异构水解酶活性水平降低或不存在，阻断视觉周期并导致视力受损。
适应症和用法
LUXTURNA是一种基于腺相关病毒载体的基因治疗，用于治疗确诊的双等位基因RPE65突变相关的视网膜营养不良患者。患者必须具有由治疗医师确定的活的视网膜细胞。
剂量和给药
仅用于视网膜下注射。
每只眼睛的LUXTURNA推荐剂量为1.5×1011个载体基因组（vg），通过视网膜下注射给药，总体积为0.3mL。
在紧密间隔内的不同日子对每只眼睛进行视网膜下LUXTURNA给药，但间隔不少于6天。
推荐1mg/kg /天（最多40mg /天）相当于强的松的全身性口服皮质类固醇，共7天（从LUXTURNA给予每只眼睛开始前3天开始），然后在下一次给药时逐渐减量10天。
剂量形式和强度
LUXTURNA是视网膜下注射的悬浮液，在单剂量2mL小瓶中以0.5mL可提取体积提供，在一只眼睛中单次给药。所提供的浓度（5×10 12vg/mL）在给药前需要1:10稀释。稀释剂由两个一次性使用的2 mL样品瓶提供。
禁忌症
没有。
警告和注意事项
眼内炎：使用适当的无菌注射技术并监测感染的体征和症状。
视网膜异常：监测黄斑异常，视网膜撕裂或断裂。不要在中央凹附近注射。
眼压升高：监测和控制眼压升高。
眼内气泡的扩张：在吸收任何眼内气泡之前，不建议进行空中旅行和/或水肺潜水。
白内障：视网膜下注射LUXTURNA可能导致白内障形成或白内障发展率增加。
不良反应
临床试验中最常见的不良反应（发生率≥5％）为结膜充血，白内障，眼压升高，视网膜撕裂，角膜基质变薄，黄斑裂孔，视网膜下沉积，眼部炎症，眼刺激，眼疼痛和黄斑病变（黄斑表面起皱）。
用于特定人群
儿科用途：不建议在12个月以下的婴儿中使用，因为在这个年龄组中由于活跃的视网膜细胞增殖而可能在给药后稀释或丢失LUXTURNA。
包装提供/存储和处理
每盒LUXTURNA（NDC 71394-415-01）包含一个单剂量的LUXTURNA小瓶（NDC 71394-065-01，0.5mL可提取体积）和两瓶稀释液（NDC 71394 - 716-01,1.7mL可萃取物）每个小瓶中的体积）。LUXTURNA每毫升含有5×1012个载体基因组（vg），在给药前需要1:10稀释。
储存LUXTURNA和稀释剂在≤-65°C冷冻。
解冻小瓶后，在室温下储存。将稀释的LUXTURNA储存在室温下[见剂量和给药方法]。
LUXTURNA是一种基于腺相关病毒载体的基因疗法。 遵循通用的生物危害预防措施进行处理。
完整说明书附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=08313a24-e7ce-457a-bb3f-161bc45517ee 
FDA Approves Spark Therapeutics' LUXTURNA(TM) (voretigene neparvovec-rzyl), a One-time Gene Therapy for Patients with Confirmed Biallelic RPE65 Mutation-associated Retinal Dystrophy (ONCE.O)
LUXTURNA is a prescription gene therapy product used for the treatment of patients with inherited retinal disease due to mutations in both copies of the RPE65 gene, which can only be confirmed through genetic testing. You must also have enough remaining cells in your retina (the thin layer of tissue in the back of your eyes) as determined by your healthcare professional.
IMPORTANT SAFETY INFORMATION
The following serious side effects may occur during or after the administration of LUXTURNA:
Eye infections, including a serious infection inside of the eye called endophthalmitis, that may lead to blindness.
Permanent decline in visual acuity, or the sharpness of central vision.
Changes in the retina (the thin layer of tissue in the back of the eye) that can lead to vision loss including:
development of a hle, thinning, or loss of function of the retina, separation of the layers in the center of the retina, or bleeding in the retina.
breaks in or wrinkling on the surface of the retina or detachment of the retina.
Increased pressure inside of the eye. You should follow-up with your healthcare professional as instructed to detect and treat any increased pressure in the eye as this may cause blindness.
Expansion of the air bubble formed in the eye after administration of LUXTURNA. You should avoid air travel, travel to high elevations, or scuba diving until your healthcare professional has told you that the air bubble formed in the eye following administration of LUXTURNA has disappeared. Engaging in these activities while the air bubble is present can cause permanent vision loss.
Formation or worsening of cataract (clouding of the lens inside of the eye).
Tell your healthcare professional right away if you have any of the following symptoms of these serious side effects:
Seeing floaters (specks that float about in your field of vision)
Pain in the eye
Any change in vision including decreased vision or blurred vision
Seeing flashes of light
The following are the most common side effects that may occur with LUXTURNA:
Redness of the eye
Cataract (clouding of the lens inside of the eye)
Increased pressure inside of the eye
Breaks in the retina
Dellen (thinning of the clear layer in the front of the eye)
Development of a hole in the center of the retina
Subretinal deposits (deposits under the retina)
Eye swelling, irritation or pain
Wrinkling on the surface of the center of the retina
Treatment with LUXTURNA is not recommended for patients younger than 12 months of age because the retina is still growing, which may affect how LUXTURNA works.
Because small quantities of LUXTURNA may be in your tears for a short period of time, for the first 7 days after administration of LUXTURNA, place any waste material from dressings, tears and nasal secretions in sealed bags prior to disposal.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. You may also report side effects to Spark Therapeutics at 1-855-SPARKTX (1-855-772-7589).
This information does not take the place of talking to your healthcare professional about your medical condition or treatment. If you have questions about LUXTURNA after reading this information, ask your healthcare professional.
INDICATION
LUXTURNA (voretigene neparvovec-rzyl) is a prescription gene therapy product used for the treatment of patients with inherited retinal disease due to mutations in both copies of the RPE65 gene, which can only be confirmed through genetic testing. You must also have enough remaining cells in your retina (the thin layer of tissue in the back of your eyes) as determined by your healthcare professional.
Please see US Full Prescribing Information for LUXTURNA
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