——新型基因治疗药物Luxturna，获FDA批准用于治疗遗传性视网膜病变（儿童和成人）患者 近日，美国FDA批准Spark Therapeutics的创新基因疗法Luxturna（voretigene neparvovec-rzyl）上市，用于治疗双等位基因RPE65突变导致的遗传性视网膜病变（IRD）的儿童和成人患者。 批准日期：2017年10月13日 公司研发：Spark Therapeutics LUXTURNA(voretigene neparvovec-rzyl)注射剂，为视网膜下注射眼内悬液 美国初次批准：2017年 作用机制 LUXTURNA被设计为输送一个正常拷贝的基因编码人视网膜色素上皮65 kDa蛋白质(RPE65)至视网膜细胞人有减低或缺失生物学上活性RPE65的水平。RPE65被产生在视网膜色素上皮(RPE)细胞和转换全反式视黄醇至11-顺式-视黄醇，它随后形成发色团[chomophore]，11-顺式-视黄醇，在视觉(维甲酸[retinoid])周期期间，视觉周期在光转换中是至关重要，这是指在视网膜中将光子的光生物转换成电信号。在RPE65基因中突变导致减低缺乏RPE65异构水解酶[isomerohydrolase]活性的水平，阻断视觉周期和导致视力的受损。 适应证和用途 LUXTURNA是一种腺伴随病毒载体-基于基因治疗适用为的治疗有被确证的双等位基因RPE65突变相关的视网膜营养不良患者。患者必须有活视网膜细胞被治疗医生们测定。 剂量和给药方法 仅为视网膜下注射。 ●LUXTURNA对每只眼的推荐剂量为1.5x1011载体基因组(vg)，通过视网膜下注射总体积0.3mL给药。 ● 进行视网膜下LUXTURNA的给药至每眼给药在分开天有一个闭合间隔内，但间隔不少于 6天。 ● 推荐的全身口服皮质激素等同于泼尼松[prednisone]在1mg/kg/day (最大40mg/day)总共7天(LUXTURNA至每眼开始前3天给予)，和接着被在下一个10天期间的锥形逐渐减小的剂量。 剂型和规格 LUXTURNA是为视网膜下注射的悬液，在一个0.5mL可提取体积内提供在一个单次-剂量 2mL小瓶为在一只眼给药。提供浓度(5x1012 vg/mL)在给药前需要一个1:10稀释。提供的稀释液在两个单次-使用2-mL小瓶. 禁忌证 无。 警告和注意事项 ● 眼内炎：使用适当无菌注射技术和监视对感染的体征和症状. ● 视力持续下降：监视视力障碍。 ● 视网膜异常：监视黄斑异常，视网膜撕裂或破裂。不要注射到黄斑附近。 ● 增加眼内压：监视和处理眼内压升高。 ● 眼内气泡扩大：不推荐航空旅行和深潜直至眼内气泡已被吸收。 ● 白内障：LUXTURNA的视网膜下注射可能导致白内障形成或白内障进程的速率增快。 不良反应 在临床试验中最常见不良反应 (发生率≥ 5%)为结膜充血，白内障，增加眼内压，视网膜撕裂，角膜凹陷[dellen](角膜基质变薄)，黄斑孔，视网膜下沉积，眼炎症，眼刺激，眼痛，和黄斑病变 (黄斑表面起皱). 在特殊人群中使用 儿童使用：不推荐在12月龄婴儿中使用因为给药后潜在稀释或LUXTURNA的丢失由于在这个年龄组中发生活性视网膜细胞增殖。 包装供应/贮存和处置 每个纸盒LUXTURNA(NDC 71394 – 415-01)含一个单次-剂量小瓶的LUXTURNA(NDC 71394 –065-01，0.5 mL 可提取的体积)和两个小瓶稀释液(NDC 71394 – 716-01，每小瓶1.7 mL可提取容积)。LUXTURNA含5 x 1012载体基因组(vg)每mL，给药前需要一个1:10 稀释。 贮存LUXTURNA和稀释液 冻结在 ≤ -65 °C. 小瓶的冻融后，贮存在室温。贮存稀释的LUXTURNA在室温 [见剂量和给药方法]。 LUXTURNA是一种一种腺伴随病毒载体-基于基因治疗。遵循通用的生物危害处理预防注意措施。 Luxturna(Voretigene Neparvovec-rzyl Intraocular Suspension for Injection) 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 first gene therapy for a genetic disease, first and only pharmacologic treatment for an inherited retinal disease (IRD) and firstadeno-associated virus (AAV) vectorgene therapy approved in U.S. Children and adults living with IRD caused by biallelicRPE65gene mutations nearly all progress to complete blindness U.S. Food and Drug Administration (FDA) has approved LUXTURNA(TM) (voretigene neparvovec-rzyl), a one-time gene therapy product indicated for the treatment of patients with confirmed biallelicRPE65mutation-associated retinal dystrophy. LUXTURNA should only be administered to patients with mutations on both copies of theRPE65gene who have sufficient viable retinal cells as determined by their treating physicians. LUXTURNA is the first FDA-approved gene therapy for a genetic disease, the first and only pharmacologic treatment for an inherited retinal disease (IRD) and the first adeno-associated virus (AAV) vector gene therapy approved in the U.S. Indication and Important Safety Information LUXTURNA (voretigene neparvovec-rzyl) is an adeno-associated virus vector-based gene therapy indicated for the treatment of patients with confirmed biallelicRPE65mutation-associated retinal dystrophy. Patients must have viable retinal cells as determined by the treating physicians. Warnings and Precautions * Endophthalmitismay occur following any intraocular surgical procedure or injection. Use proper aseptic injection technique when administering LUXTURNA, and monitor for and advise patients to report any signs or symptoms of infection or inflammation to permit early treatment of any infection. * Permanent decline in visual acuitymay occur following subretinal injection of LUXTURNA. Monitor patients for visual disturbances. * Retinal abnormalitiesmay occur during or following the subretinal injection of LUXTURNA, including macular holes,foveal thinning, loss of foveal function, foveal dehiscence, and retinal hemorrhage. Monitor and manage these retinal abnormalities appropriately. Do not administer LUXTURNA in the immediate vicinity of the fovea. Retinal abnormalities may occur during or following vitrectomy, including retinal tears, epiretinal membrane, or retinal detachment. Monitor patients during and following the injection to permit early treatment of these retinal abnormalities. Advise patients to report any signs or symptoms of retinal tears and/or detachment without delay. * Increased intraocular pressuremay occur after subretinal injection of LUXTURNA. Monitor and manage intraocular pressure appropriately. * Expansion of intraocular air bubblesInstruct patients to avoid air travel, travel to high elevations or scuba diving until the air bubble formed following administration of LUXTURNA has completely dissipated from the eye. It may take one week or more following injection for the air bubble to dissipate. A change in altitude while the air bubble is still present can result in irreversible vision loss. Verify the dissipation of the air bubble through ophthalmic examination. * CataractSubretinal injection of LUXTURNA, especially vitrectomy surgery, is associated with an increased incidence of cataract development and/or progression. Adverse Reactions * In clinical studies, ocular adverse reactions occurred in 66% of study participants (57% of injected eyes), and may have been related to LUXTURNA, the subretinal injection procedure, the concomitant use of corticosteroids, or a combination of these procedures and products. * The most common adverse reactions (incidence greater than or equal to5% of study participants) were conjunctival hyperemia (22%), cataract (20%), increased intraocular pressure (15%), retinal tear (10%), dellen (thinning of the corneal stroma) (7%), macular hole (7%), subretinal deposits (7%), eye inflammation (5%), eye irritation (5%), eye pain (5%), and maculopathy (wrinkling on the surface of the macula) (5%). Immunogenicity Immune reactions and extra-ocular exposure to LUXTURNA in clinical studies were mild. No clinically significant cytotoxic T-cell response to either AAV2 or RPE65 has been observed. Study participants received systemic corticosteroids before and after subretinal injection of LUXTURNA to each eye, which may have decreased the potential immune reaction to either AAV2 or RPE65. Pediatric Use Treatment with LUXTURNA is not recommended for patients younger than 12 months of age, because the retinal cells are still undergoing cell proliferation, and LUXTURNA would potentially be diluted or lost during the cell proliferation. The safety and efficacy of LUXTURNA have been established in pediatric patients. There were no significant differences in safety between the different age subgroups.