An Open-label, Multicenter, Phase 2 Follow-on Study for Second Eye Treatment of Patients Previously Treated With a Recombinant Adeno-associated Virus Vector (AAV5 hRKp.RPGR) for Gene Therapy of Adults and Children With X-linked Retinitis Pigmentosa Owing to Defects in Retinitis Pigmentosa GTPase Regulator (RPGR)

The purpose of this study is to assess the safety and tolerability of subretinal delivery of Adeno-associated Virus Vector (AAV5 hRKp.RPGR) gene therapy in adults and children with X-linked retinitis pigmentosa.

开始日期2024-10-11

申办/合作机构

Janssen Research & Development LLC

NCT06492850 / Recruiting临床1/2期

A Phase I/II Dose-escalation and Dose-expansion Study to Evaluate the Safety and Efficacy of FT-002 Subretinal Injection in Subjects With RPGR Gene Mutation-associated X-linked Retinitis Pigmentosa.

The aim of this study was to evaluate the safety, tolerability, and efficacy of one-time subretinal injection of FT-002 in male subjects (8-45 years of age) with RPGR (Retinitis Pigmentosa GTPase Regulator) gene mutation-associated X-linked retinitis pigmentosa, of XLRP. This study includes Phase I (dose escalation phase) and Phase II (dose expansion phase).

开始日期2024-04-01

申办/合作机构

Frontera Therapeutics, Inc.初创企业

NCT04850118 / Recruiting临床2/3期

A Randomized, Controlled, Masked, Multi-center Study Evaluating the Efficacy, Safety, and Tolerability of Two Doses of AGTC-501 Compared to an Untreated Control Group in Male Participants With X-linked Retinitis Pigmentosa

This study will evaluate and compare the safety, efficacy, and tolerability of 2 doses of a recombinant adeno-associated virus vector (AGTC-501) to an untreated control group in male participants with X-linked retinitis pigmentosa caused by RPGR mutations.

开始日期2024-03-14

申办/合作机构-

100 项与 X连锁视网膜色素变性相关的临床结果

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100 项与 X连锁视网膜色素变性相关的转化医学

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0 项与 X连锁视网膜色素变性相关的专利（医药）

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项与 X连锁视网膜色素变性相关的文献（医药）

2024-11-01·American Journal of Ophthalmology

Phase 1/2 AAV5-hRKp.RPGR (Botaretigene Sparoparvovec) Gene Therapy: Safety and Efficacy in RPGR-Associated X-Linked Retinitis Pigmentosa

Article

作者: Georgiadis, Anastasios ; Ripamonti, Caterina ; Besirli, Cagri G ; Clark, Michael ; Ali, Robin R ; Huckfeldt, Rachel M ; Sahel, José-Alain ; DE Guimaraes, Thales A C ; Kumaran, Neruban ; Anglade, Eddy ; Fleck, Penny R ; Minnick, Pansy ; Smith, Alexander J ; Bainbridge, James ; Fung, Albert ; Xu, Jialin ; Forbes, Alexandria ; Peluso, Colleen ; Georgiou, Michalis ; Naylor, Stuart ; Michaelides, Michel ; Kalitzeos, Angelos ; Wong, Peggy ; Wong, Sui Chien ; Comander, Jason I ; Tee, James J L ; Zeldin, Robert ; Yang, Yesa ; Shah, Syed Mahmood

PURPOSETo assess the safety and efficacy of AAV5-hRKp.RPGR in participants with retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis pigmentosa (XLRP).DESIGNOpen-label, phase 1/2 dose escalation/expansion study (ClinicalTrials.gov Identifier: NCT03252847).METHODSMales (≥5 years old) with XLRP-RPGR were evaluated. In the dose escalation phase, subretinal AAV5-hRKp.RPGR (low: 1.0 × 10¹¹ vg/ml; intermediate: 2.0 × 10¹¹ vg/ml; high: 4.0 × 10¹¹ vg/ml) was administered to the poorer-seeing eye (n = 10). Dose confirmation (intermediate dose) was carried out in 3 pediatric participants. In the dose expansion phase, 36 participants were randomized 1:1:1 to immediate (low or intermediate dose) or deferred (control) treatment. The primary outcome was safety. Secondary efficacy outcomes included static perimetry, microperimetry, vision-guided mobility, best corrected visual acuity, and contrast sensitivity. Safety and efficacy outcomes were assessed for 52 weeks for immediate treatment participants and 26 weeks for control participants.RESULTSAAV5-hRKp.RPGR was safe and well tolerated, with no reported dose-limiting events. Most adverse events (AEs) were transient and related to the surgical procedure, resolving without intervention. Two serious AEs were reported with immediate treatment (retinal detachment, uveitis). A third serious AE (increased intraocular pressure) was reported outside the reporting period. All ocular inflammation-related AEs responded to corticosteroids. Treatment with AAV5-hRKp.RPGR resulted in improvements in retinal sensitivity and functional vision compared with the deferred group at Week 26; similar trends were observed at Week 52.CONCLUSIONSAAV5-hRKp.RPGR demonstrated an anticipated and manageable AE profile through 52 weeks. Safety and efficacy findings support investigation in a phase 3 trial.

2024-10-01·Value in Health

Challenges in Value Assessment for One-Time Gene Therapies for Inherited Retinal Diseases: Are We Turning a Blind Eye?

Article

作者: Alulis, Sarah ; Hitch, Jake ; Lee, Jennifer ; Steuten, Lotte ; Denee, Tom ; Petersen, Jacob ; Brassel, Simon ; Michaelides, Michel

OBJECTIVESX-linked retinitis pigmentosa (XLRP) is a rare inherited retinal disease with no available treatment. Gene therapies in clinical trials will pose challenges for HTA if found to be safe and effective. We examine two of these challenges, namely acceptability and difficulties in assessing value beyond short-term patient health and healthcare savings, and discounting in economic evaluation.METHODSWe conducted a narrative literature review on the socioeconomic burden of XLRP to identify relevant components of value for a hypothetical gene therapy from a societal perspective, and to assess their relative importance. We compared the resulting value profile against the value frameworks of three European HTA agencies. We also reviewed their guidelines on discounting and potential discounting issues specific to XLRP.RESULTSMuch of the societal value of an XLRP gene therapy is likely to originate from productivity effects, carer spillovers, and value elements related to patient uncertainty. However, the evidence on these effects is often limited, making it difficult for HTA agencies to assess them. Cost-effectiveness results are likely to be highly sensitive to the discount rate, and discounting will compound the effects of omitting important sources of value.CONCLUSIONSWe have identified and detailed important components of societal value, key evidence gaps, and potential discounting issues for an XLRP gene therapy which can inform future value assessments. Many of these may apply to gene therapies in other disease areas. Revisiting existing HTA approaches is recommended to ensure these are fit for purpose for such new classes of treatment.

2024-09-17·Translational Vision Science & Technology

Establishing Clinical Trial Endpoints in Selecting Patients for RPGR Retinal Gene Therapy

Article

作者: Josan, Amandeep S. ; Cehajic-Kapetanovic, Jasmina ; MacLaren, Robert E. ; Christou, Evita Evangelia

PurposeClinical trials for X-linked retinitis pigmentosa (RP) often assess retinal structure using optical coherence tomography (OCT) and function using microperimetry to evaluate initial eligibility and endpoints. Therefore, we seek to determine which parameters might be most sensitive in screening new patients for enrollment.MethodsThirty-one patients (62 eyes) with confirmed retinitis pigmentosa GTPase regulator (RPGR) mutations attending Oxford Eye Hospital were included in this retrospective analysis. Outer retinal structure was investigated by measuring the remaining ellipsoid zone (EZ) and external limiting membrane (ELM) on OCT. Visual function was evaluated by using 10-2 microperimetry mean sensitivity.ResultsThe median age of patients with RPGR was 31 years (interquartile range [IQR] = 22-39 years). For the right and left eyes, respectively, the median EZ length through the foveal section was 921 µm (IQR = 607-1570) and 865 µm (IQR = 508-1442) and median ELM length was 2056 µm (IQR = 1336-2764) and 1860 µm (IQR = 1152-2680). Similarly, the median microperimetry sensitivity (MS) was 2.0 decibel (dB; IQR = 0.4-5.4) and 1.1 dB (IQR = 0.1-5.4). Linear mixed model regression analysis showed that EZ was significantly positively correlated to ELM (P < 0.001, R² = 0.931). EZ and ELM were significantly correlated with the microperimetry sensitivity with exponential relationship (P < 0.001, R² = 0.71 and 0.72, respectively). Using the exponential equation of regression line, EZ below approximately 600 µm (RE = 637 µm, 95% confidence interval [CI] = 397-877, LE = 586 µm, 95% CI = 356-817) results in microperimetry sensitivity of approximately 0 dB. There was high degree of inter-eye symmetry for progression of EZ, ELM, and microperimetry sensitivity. Age was significantly correlated with the analyzed parameters (P < 0.001), although with low R² for each of them.DiscussionEZ may comprise a surrogate biomarker for prediction of visual function in X-linked RP caused by mutations in RPGR and, in turn, identification of appropriate patients for enrollment in clinical trials. As expected, age plays a role in predicting potential biomarkers and visual function, however, it should not be used to preclude patients for gene therapy due to the poor correlation and heterogeneity of disease onset.Translational RelevanceBiomarkers of visual function in RPGR-associated RP may lead to identification of appropriate patients for enrollment in clinical trials.

项与 X连锁视网膜色素变性相关的新闻（医药）

2024-10-19

·药明康德

使94%患儿病情稳定的基因疗法；缓解持续三年的细胞疗法…… | CGT周报

▎药明康德内容团队编辑近期，全球细胞和基因疗法（CGT）领域迎来系列进展。美国FDA批准的首款脑性肾上腺脑白质营养不良（CALD）基因疗法Skysona的长期研究结果积极，中位随访时间超过6年，94%患者的神经功能没有下降。用于治疗杜氏肌营养不良（DMD）的细胞疗法deramiocel在一项临床试验中使患者的心脏和骨骼肌功能在三年期间趋于稳定，其上市申请有望在今年年底前完成递交。首个进入人体临床试验的工程化B细胞疗法ISP-001的初步结果积极，首位接受治疗的1型黏多糖贮积症（MPS I）患者已停止使用标准疗法。本文将节选其中部分重要进展做简单介绍，仅供读者参阅。图片来源：123RF ———✦研发进展✦——— ◇ 近日，《新英格兰医学杂志》（NEJM）上刊登了两篇论文，公布了美国FDA批准的首款脑性肾上腺脑白质营养不良基因疗法Skysona（elivaldogene autotemcel，也称为eli-cel）的长期随访结果。首批在临床试验中接受eli-cel治疗的CALD患儿的中位随访时间已超过6年。长期疗效数据显示，eli-cel能够控制这种神经系统疾病的进展，94%患者的神经功能没有下降，超过80%的患者没有出现严重残疾。 CALD是一种罕见的X染色体连锁遗传性脑部疾病，主要发生于男孩。该病患儿因ABCD1基因突变导致过氧化物酶体功能缺失，大量异常的极长链脂肪酸（VLCFAs）会沉积于大脑白质和肾上腺，从而导致患儿进行性、不可逆的神经功能丧失，最终过早死亡。Eli-cel利用Lenti-D慢病毒载体，在体外将ABCD1基因的功能性拷贝导入到患者自身的造血干细胞中，再输回到患者体内，从而促进VLCFAs分解、避免毒性积累。 ◇ Capricor Therapeutics公司公布了其主打细胞疗法deramiocel（CAP-1002）治疗不能行动的晚期DMD患者的HOPE-2开放标签扩展（OLE）试验的三年积极结果。HOPE-2试验达成其主要终点，即在测试上肢功能的指标PUL 1.2上，接受CAP-1002治疗的病患有显著疗效（2.6分差异，P=0.014）。OLE试验的分析显示，接受deramiocel治疗患者的心脏和骨骼肌功能在三年期间趋于稳定。Capricor预计在今年年底前完成递交该疗法用于治疗DMD相关心肌病患者的生物制品许可申请（BLA）。 CAP-1002是一种同种异体的细胞疗法，它们由心脏来源细胞（CDCs）组成，CDCs是一种含有心脏祖细胞的特殊细胞群。它们通过释放包含微RNA、非编码RNA和蛋白的外泌体，改善DMD患者肌肉瘢痕或纤维化以及心脏功能。CAP-1002还显示出有效的免疫调节活性，可能促进细胞再生。目前美国FDA已授予CAP-1002再生医学先进疗法认定与孤儿药资格。 ◇ MeiraGTx公司公布了在研帕金森病基因疗法AAV-GAD在随机双盲、安慰剂对照临床试验MGT-GAD-025中的顶线数据。在这项试验中，帕金森病患者接受双侧丘脑底核AAV-GAD输注或安慰剂。初步数据显示，AAV-GAD达到了安全性和耐受性的主要终点。此外，接受AAV-GAD治疗26周后，患者在运动能力和生活质量方面均获得统计显著并具有临床意义的改善。 AAV-GAD是一款在研基因疗法，能将编码谷氨酸脱羧酶（GAD）的转基因递送至丘脑底核，以增加人脑中的主要抑制性神经递质GABA的产生。GAD是GABA合成中的限速酶，因此通过基因疗法增加丘脑底核GAD的表达，将导致运动回路正常化，并改善帕金森病的症状，同时不影响其他可能造成现有疗法并发症的大脑区域。 ◇ Beacon Therapeutics公司公布了其在研基因疗法AGTC-501在治疗X连锁视网膜色素变性（XLRP）的2期临床试验SKYLINE中获得的积极结果。在接受治疗24个月后，接受高剂量AGTC-501治疗的眼睛的缓解率达到57%。接受低剂量AGTC-501治疗的眼睛的缓解率为25%。AGTC-501表现出良好的安全性和耐受性，治疗伴发不良事件的大多为轻度或中度。 XLRP是一种遗传性单基因隐性疾病，会导致男孩和年轻男性视力逐渐丧失。XLRP主要由视网膜色素变性GTPase调节剂（RPGR）基因突变引起。AGTC-501表达全长RPGR蛋白，从而解决XLRP引起的感光细胞损伤，包括视杆细胞和视锥细胞的丧失。图片来源：123RF ◇ Immusoft公司公布了首位接受其工程化B细胞疗法ISP-001治疗的1型黏多糖贮积症患者的积极结果。根据新闻稿，ISP-001是首个进入人体临床试验的工程化B细胞疗法。该疗法使用非病毒载体将表达α-L-艾杜糖苷酶的转基因引入B细胞中，能够让经过改造的B细胞长期大量生产治疗性蛋白，从而改善患者症状。初步数据显示，该患者的疾病生物标志物指标获得改善，在接受一次ISP-001治疗8个月后，已停止使用标准酶替代疗法（ERT）。 ◇ 中国国家药监局药品审评中心（CDE）官网最新公示，合源生物纳基奥仑赛注射液获批一项临床试验默示许可，针对适应症为难治性系统性红斑狼疮相关的免疫性血小板减少症（SLE-ITP）。纳基奥仑赛为靶向CD19嵌合抗原受体自体T（CD19 CAR-T）细胞注射液。根据合源生物新闻稿，这也是该产品在自身免疫性疾病治疗领域获得的第一张IND批件。今年7月，《新英格兰医学杂志》在线发表了纳基奥仑赛治疗SLE-ITP的案例报道。1名此前曾接受过大量治疗的SLE-ITP女性患者在接受纳基奥仑赛注射液回输后的第28天，血液中的CD19阳性B细胞被清除，第三个月时B细胞获得重建。患者的血小板计数在治疗后的六个月内持续上升，并达到临床完全缓解。此外，患者停用了糖皮质激素和所有免疫抑制剂。 ◇ 原天生物1类生物制品新药YT001注射液在中国获批临床，拟开发治疗膝骨关节炎（KOA）。根据原天生物新闻稿介绍，YT001是其研发的一款间充质干细胞治疗产品。间充质干细胞具有免疫调节作用，能够缓释炎症反应，促进损伤修复，其免疫调节和损伤修复功能可帮助调节关节腔内紊乱微环境，缓解软骨的降解。 ◇ 因诺惟康宣布，其自主研发的可玻璃体内给药的基因疗法IVB103注射液获得了CDE的临床许可，旨在治疗新生血管性年龄相关性黄斑变性（nAMD）。IVB103通过该公司的EASI-FIND腺相关病毒（AAV）发现平台开发，具有“best-in-class”的潜力。今年7月，IVB103注射液获得了FDA的IND许可，用于同样的适应症。 ◇ 瑞风生物申报的RM-101注射液在中国获批临床，拟开发用于治疗USH2A基因外显子13突变所致的Usher综合征2型相关视网膜色素变性（RP）或非综合征型RP。Usher综合征是与视网膜色素变性有关的最常见综合征，USH2A基因突变导致视网膜色素变性，患者通常在青少年时期逐渐出现夜盲和周边视野缺失，最终可能导致全盲。根据瑞风生物公开资料介绍，RM-101是基于AAV的基因编辑类药物，能特异靶向USH2A基因转录的RNA，调控可变剪接生物学过程，诱导功能正常蛋白的表达恢复。该产品通过视网膜下注射给药，有望实现一次性给药并长期有效。 ◇ 恒瑞医药子公司瑞宏迪医药申报的1类新药RGL-193注射液在中国获批临床，拟开发治疗帕金森病。公开资料显示，RGL-193是瑞宏迪医药针对帕金森病自主研发的一款AAV双基因药物，采用立体定向技术注入患者脑内。它可以提高左旋多巴的转化效率，同时还起到保护和修复受损多巴胺能神经元的作用，具有潜在的延缓病情进展、减少口服抗帕金森病药量的效果。 ◇ 艺妙医疗申报的CAR-T细胞注射液IM96在中国获批临床，拟开发用于治疗结直肠癌。根据艺妙医疗新闻稿介绍，IM96是其与北京大学肿瘤医院合作开发用于治疗转移性结直肠癌的全新一代抗肿瘤药物，是一款靶向鸟苷酸环化酶2C（GUCY2C）的CAR-T疗法。该产品的临床前研究数据于今年6月入选美国临床肿瘤学会（ASCO）年会，研究显示IM96针对结直肠癌的最佳客观缓解率（ORR）达到50%，且仅有5.0%的患者出现神经毒性和≥3级的细胞因子释放综合征（CRS）。 ———✦融资、合作、M&A✦——— 图片来源：123RF ◇ Tolerance公司宣布完成了1720万美元的种子轮融资，本轮融资由Columbus Venture Partners领投，Criteria Bio Ventures、Sessa Capital、BioAdvance、Ben Franklin Technology Partners等投资者参投。该公司正在开发一种以同种异体或“现货型”胸腺诱导多能干细胞（iPSC）为基础的细胞疗法平台和胸腺疗法，旨在延缓和预防人体免疫系统中的重要器官胸腺的衰退，并在胸腺功能丧失时恢复其功能，以治疗由免疫耐受异常引起的免疫介导疾病，包括癌症、自身免疫疾病、移植排斥、感染、免疫缺陷和过敏。 ◇ 睿健医药宣布完成超亿元B轮融资，该资金将用于加速其帕金森病治疗产品NouvNeu001/NouvNeu003，以及眼科治疗产品NouvSight001的中美临床推进，加强公司多款创新管线的研发推进和临床能力的搭建，以及加大公司产业化建设的力度。 NouvNeu001是一款源于iPSC，化学诱导分化的多巴胺能神经元前体细胞。新闻稿指出，NouvNeu001是帕金森领域中，全球首个进入临床阶段的基于化学诱导的通用型细胞治疗产品，其IND申请已在中美两地获批。其早发型帕金森产品NouvNeu003的1期临床试验也即将完成剂量拓展阶段，实现睿健医药覆盖帕金森病全病程的重要一步。NouvSight001是睿健医药团队依托公司独特的“AI+化学诱导”平台开发的首款iPSC来源眼科通用型细胞治疗产品，旨在针对视网膜色素变性系列适应症。该产品于今年3月获得了美国FDA授予的孤儿药资格。 ◇ Eterna Therapeutics公司与Factor Bioscience公司宣布达成一项独家许可与合作协议，旨在加速开发治疗肿瘤、罕见病和自身免疫疾病的候选细胞疗法。根据协议条款，Eterna公司获得了一项全球独家许可，利用Factor公司的细胞重编程和基因编辑技术，开发某些基于iPSC的细胞疗法产品，尤其是iPSC衍生的间充质干细胞（iMSC），该细胞经过工程化处理可表达某些细胞因子。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] Florian Eichler, et al., (2024). Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy. The N Engl J Med, DOI: 10.1056/NEJMoa2400442 [2] Christine N. Duncan, et al., (2024). Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy. The N Engl J Med, DOI: 10.1056/NEJMoa2405541 [3] Capricor Therapeutics Announces Positive Long-Term Data from HOPE-2 OLE Study in Duchenne Muscular Dystrophy at 2024 World Muscle Society Congress. Retrieved October 11, 2024 from https://www.globenewswire.com/news-release/2024/10/11/2962050/0/en/Capricor-Therapeutics-Announces-Positive-Long-Term-Data-from-HOPE-2-OLE-Study-in-Duchenne-Muscular-Dystrophy-at-2024-World-Muscle-Society-Congress.html [4] Beacon Therapeutics Announces Positive 24-Month Data from Phase 2 SKYLINE Trial of AGTC-501 in Patients with X-Linked Retinitis Pigmentosa. Retrieved October 15, 2024, from https://www.prnewswire.com/news-releases/beacon-therapeutics-announces-positive-24-month-data-from-phase-2-skyline-trial-of-agtc-501-in-patients-with-x-linked-retinitis-pigmentosa-302275688.html [5] MeiraGTx Announces Positive Data from Randomized, Sham-controlled Clinical Bridging Study of AAV-GAD for the Treatment of Parkinson’s Disease. Retrieved October 15, 2024, from https://investors.meiragtx.com/news-releases/news-release-details/meiragtx-announces-positive-data-randomized-sham-controlled [6] Immusoft to Announce Positive Phase 1 Data for First Engineered B Cell Therapy in a Clinical Trial. Retrieved October 15, 2024, from https://www.prnewswire.com/news-releases/immusoft-to-announce-positive-phase-1-data-for-first-engineered-b-cell-therapy-in-a-clinical-trial-302255551.html [7] 合源生物纳源瑞达®新增自身免疫性疾病适应症新药临床试验（IND）申请获默示许可. Retrieved October 11, 2024, from https://mp.weixin.qq.com/s/9-w9DlWNPKFMdZ8KjxGz7g [8]中国国家药监局药品审评中心（CDE）官网. Retrieved October 13, 2024, from https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c [9] Tolerance Bio, Inc. Launches With $17.2 Million in Seed Financing to Advance Thymus-Based Therapies for Immune-Mediated Diseases. Retrieved October 18, 2024, from https://www.businesswire.com/news/home/20241008134130/en/Tolerance-Bio-Inc.-Launches-With-17.2-Million-in-Seed-Financing-to-Advance-Thymus-Based-Therapies-for-Immune-Mediated-Diseases#:~:text=Tolerance%20Bio%2C%20Inc.%20Launches%20With%20%2417.2%20Million%20in,manipulation%20platforms%20to%20prevent%20and%20treat%20immune%20diseases [10] 睿健医药完成超亿元B轮融资，加速国际化进程. Retrieved October 18, 2024, from https://mp.weixin.qq.com/s/gIxbOkl79mn2_OSK0bAs1w [11] Eterna Therapeutics and Factor Bioscience Announce Exclusive License and Collaboration Agreement to Accelerate Cell Therapy Development for Oncology, Autoimmune, and Rare Diseases. Retrieved October 18, 2024, from https://www.globenewswire.com/news-release/2024/10/17/2964799/0/en/Eterna-Therapeutics-and-Factor-Bioscience-Announce-Exclusive-License-and-Collaboration-Agreement-to-Accelerate-Cell-Therapy-Development-for-Oncology-Autoimmune-and-Rare-Diseases.html [12] 因诺惟康IVB103注射液获得CDE临床许可. Retrieved October 18, 2024, from https://mp.weixin.qq.com/s/OU_bxfT9u4a_-Cs6WreoDQ 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

孤儿药基因疗法细胞疗法临床研究

2024-10-15

·药明康德

帕金森病基因疗法显著改善患者功能，眼科基因疗法2年疗效积极……

▎药明康德内容团队编辑 MeiraGTx公司帕金森病基因疗法26周临床结果积极 MeiraGTx公司今日公布了在研帕金森病基因疗法AAV-GAD在随机双盲、安慰剂对照临床试验MGT-GAD-025中的顶线数据。在这项试验中，帕金森病患者接受双侧丘脑底核AAV-GAD输注或安慰剂。初步数据显示，AAV-GAD达到了安全性和耐受性的主要终点。此外，接受治疗26周后，关键性疗效终点获得统计显著并具有临床意义的改善。其中，接受高剂量AAV-GAD治疗的患者组在用于评估运动能力的MDS-UPDRS第三部分评分方面与基线相比平均改善18分（p=0.03）。在第26周，高剂量和低剂量组在帕金森病患者生活质量问卷（PDQ-39）评分方面与基线相比均表现出显著改善，安慰剂组无显著变化。 AAV-GAD是一款在研基因疗法，能将编码谷氨酸脱羧酶（GAD）的转基因递送至丘脑底核，以增加人脑中的主要抑制性神经递质GABA的产生。GAD是GABA合成中的限速酶，因此通过基因疗法增加丘脑底核GAD的表达，将导致运动回路正常化，并改善帕金森病的症状，同时不影响其他可能造成现有疗法并发症的大脑区域。发现创新分子胶，辉瑞达成15亿美元研发合作 TRIANA Biomedicines今日宣布与辉瑞（Pfizer）公司达成一项战略合作与许可协议，在多种疾病领域（包括肿瘤学）共同开发创新分子胶降解剂。根据合作协议条款，TRIANA将获得4900万美元的预付款，并有资格获得超过15亿美元的潜在里程碑付款。TRIANA将利用其靶点优先和邻近优先（proximity-first）的分子胶发现平台，针对多个靶点发现分子胶降解剂。 TRIANA将负责潜在候选药物的发现工作。辉瑞拥有排他性选择权，可以获得独家许可并进一步推进临床前和临床开发。 57%缓解率，眼科基因疗法展现长期疗效 Beacon Therapeutics公司今日宣布，在研基因疗法AGTC-501在治疗X连锁视网膜色素变性（XLRP）的2期临床试验SKYLINE中获得积极结果。在接受治疗24个月后，接受高剂量AGTC-501治疗的眼睛的缓解率达到57%。接受低剂量AGTC-501治疗的眼睛的缓解率为25%。AGTC-501表现出良好的安全性和耐受性，治疗伴发不良事件的大多为轻度或中度。 AGTC-501是Beacon的主打项目，正在进行治疗XLRP的注册性临床试验。XLRP是一种遗传性单基因隐性疾病，会导致男孩和年轻男性视力逐渐丧失。XLRP主要由视网膜色素变性GTPase调节剂（RPGR）基因突变引起。AGTC-501表达全长RPGR蛋白，从而解决XLRP引起的感光细胞损伤，包括视杆细胞和视锥细胞的丧失。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料： [1] Beacon Therapeutics Announces Positive 24-Month Data from Phase 2 SKYLINE Trial of AGTC-501 in Patients with X-Linked Retinitis Pigmentosa. Retrieved October 15, 2024, from https://www.prnewswire.com/news-releases/beacon-therapeutics-announces-positive-24-month-data-from-phase-2-skyline-trial-of-agtc-501-in-patients-with-x-linked-retinitis-pigmentosa-302275688.html [2] MeiraGTx Announces Positive Data from Randomized, Sham-controlled Clinical Bridging Study of AAV-GAD for the Treatment of Parkinson’s Disease. Retrieved October 15, 2024, from https://investors.meiragtx.com/news-releases/news-release-details/meiragtx-announces-positive-data-randomized-sham-controlled [3] TRIANA Biomedicines and Pfizer Enter Into A Research Collaboration to Discover Novel Molecular Glue Degraders for Multiple Disease Areas. Retrieved October 15, 2024, from https://trianabio.com/press-release-10152024 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

基因疗法引进/卖出临床2期

2024-10-15

·PipelineReview

Beacon Therapeutics Announces Positive 24-Month Data from Phase 2 SKYLINE Trial of AGTC-501 in Patients with X-Linked Retinitis Pigmentosa

LONDON, UK and CAMBRIDGE, MA, USA I October 15, 2024 I Beacon Therapeutics Holdings Limited (‘Beacon Therapeutics’ or ‘the Company’), a leading ophthalmic gene therapy company with a purpose to save and restore the vision of patients with blinding retinal diseases, today announced the presentation of 24-month interim safety and efficacy results of the Phase 2 SKYLINE trial in patients with XLRP at the American Academy of Ophthalmology’s Annual Meeting in Chicago, Illinois. The 24-month data showed a response rate of 57% (4/7) in study eyes treated with a high dose (6.8 E+11 vg/eye) of AGTC-501, defined as a patient who has an improvement in retinal sensitivity as assessed by microperimetry of at least 7 decibels (dB) in at least 5 loci. Patients in the high-dose cohort also showed a robust improvement in mean retinal sensitivity. Study eyes treated with a low dose (7.5 E+10 vg/eye) of AGTC-501 showed a response rate of 25% (1/4). There were no clinically significant safety events associated with AGTC-501 treatment in this trial, and any treatment-emergent adverse events were mostly non-serious and mild to moderate in severity. XLRP is a severe, aggressive, inherited retinal disease that often leads to blindness by middle age, with no treatment options available. XLRP primarily affects an estimated 3.4 – 4.4 per 100,000 young males with RPGR mutations in US, Europe and Australia. AGTC-501 expresses the full length RPGR protein and is therefore expected to address the entirety of photoreceptor damage caused by XLRP, including both rod and cone loss, making it uniquely well-suited to improve the lives of patients with XLRP as a potential treatment. Lance Baldo, MD, Chief Executive Officer of Beacon Therapeutics, stated, “Our Phase 2 SKYLINE 24-month data reinforces AGTC-501’s favorable safety profile and robust improvements in mean retinal sensitivity. We will continue to assess the long-term safety and durability of AGTC-501 but are encouraged by the results we’ve seen in the SKYLINE trial to date.” Beacon Therapeutics is also enrolling its pivotal Phase 2/3 VISTA and open-label Phase 2 DAWN trials as the Company progresses toward the development of a treatment for XLRP. Poster – Subretinal AGTC-501 Gene Therapy for XLRP: 24-Month Interim Results of the Phase 2 SKYLINE Trial. Presenting Author – Robert Sisk, MD, FACS, FASRS, Associate Professor of Ophthalmology at the University of Cincinnati; Vitreoretinal Surgeon and partner at Cincinnati Eye Institute; Director of Pediatric Retinal Surgery and Director of Ophthalmic Genetics at Cincinnati Children’s Hospital. Contact: info@beacontx.com Media: beacontherapeutics@edelman.com About Beacon Therapeutics Beacon Therapeutics is an ophthalmic gene therapy company founded in 2023 to save and restore the vision of patients with a range of prevalent and rare retinal diseases that result in blindness. The Company has an established scientific foundation that combines a late-stage development candidate to treat X-linked retinitis pigmentosa (XLRP), as well as two preclinical programs, one targeting dry age-related macular degeneration (AMD) and another targeting an inherited cone-rod dystrophy (CRD). Beacon Therapeutics also has access to a target generation technology platform that will identify, screen, and search secreted proteins in the ophthalmology space. Lead development candidate AGTC-501, is a gene therapy program currently being investigated for the treatment of XLRP, an inherited monogenic recessive disorder that causes progressive vision loss, primarily in boys and young men. XLRP is predominantly caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. AGTC-501 expresses the full length RPGR protein, thereby addressing the full complement of photoreceptor damage caused by XLRP, including both rod and cone loss. Beacon is supported by funds from Syncona Limited, Forbion, Oxford Science Enterprises, TCGX, Advent Life Sciences and additional investors. Find out more about Beacon Therapeutics at beacontx.com. SOURCE: Beacon Therapeutics Holdings

临床2期临床结果基因疗法