Biallelic RPE65 mutation associated retinal dystrophy

COLUMBUS, Ohio, Oct. 9, 2024 /PRNewswire/ -- Andelyn Biosciences, Inc., a leading and patient-focused cell and gene therapy Contract Development and Manufacturing Organization (CDMO), has been selected by Hubble Therapeutics, LLC, to manufacture adeno-­associated virus (AAV) using its suspension AAV Curator™ Platform to manufacture clinical grade AAV for the treatment of Leber Congenital Amaurosis 16 ("LCA16"). LCA16 is a severe, early-onset retinal dystrophy resulting from mutations in the KCNJ13 gene, which expresses a critical ion channel in the retinal pigment epithelium cells in the retina. Children typically present with visual abnormalities within five years after birth, followed by progressive retinal degeneration during the next two decades of life, ultimately resulting in blindness. HUB-101 has received Rare Pediatric Disease Designation and Orphan Disease Designation from the FDA for this program. Andelyn will optimize and scale-up the HUB-101 process, generate GMP-grade plasmids, and produce GMP vectors that include normal copies of the KCNJ13 gene. From this partnership, Hubble Therapeutics LLC ("HubbleTx") will be able to conduct Phase 1/2 clinical trials with the intention to demonstrate safety and efficacy in an adult patient population. "Over the past 18 months we have identified best-in-class partners including Andelyn Biosciences to establish a gene therapy development program for adult and pediatric patients suffering from Leber Congenital Amaurosis 16 (LCA16)," said Jeff Sabados, President of Hubble Therapeutics LLC. Sabados continued, "Andelyn Biosciences has become a global leader in gene therapy development for ultra-rare and orphan diseases and we are grateful for their unwavering commitment toward helping Hubble Therapeutics realize our steadfast promise to support families throughout the world impacted by this devastating genetic disease." Matt Niloff, Chief Commercial Officer at Andelyn Biosciences said, "We are extremely grateful for the opportunity to produce the clinical grade material for HUB-101 and be a critical part of the pathway for Hubble Therapeutics to demonstrate clinical benefit for the LCA16 program. We are thrilled that our establishment as a top clinical and commercial CDMO is helping to accelerate so many programs like HUB-101 which offer real hope to patients stricken with debilitating diseases." With exceptional quality and scalable end-to-end development and manufacturing capabilities across its three facilities located in and near Columbus, Ohio, Andelyn continues to partner with premier innovator organizations like Hubble Therapeutics to enable the development of life-altering gene therapies for rare and prevalent diseases. About Andelyn Biosciences, Inc. Andelyn Biosciences is a full-service cell and gene therapy CDMO focused on the development, characterization and production of viral vectors for gene therapy. With more than 20 years of experience, Andelyn's deep scientific expertise has resulted in the production of cGMP material for more than 450 clinical batches and 75 global clinical trials. Operating out of three Columbus, Ohio facilities, Andelyn supports its clients in developing cell and gene therapies from concept through plasmid engineering and manufacturing, process and analytical development, and cGMP clinical and commercial manufacturing. Andelyn can accelerate programs and deliver high quality products by developing and manufacturing processes on its configurable, data-driven AAV Curator™ Platform, or tech transfer in an established client program. Capabilities include cGMP manufacturing for both adherent and suspension processes up to a 2,000-liter capacity. A rigorous quality system, regulatory support and supply chain vertical integration further support clients in bringing their critical therapies to market. For more information, visit andelynbio.com. About Hubble Therapeutics, LLC Hubble Therapeutics LLC ("HubbleTx") is a patient-focused biotechnology company developing research out of Professor Bikash Pattnaik's lab at University of Wisconsin-Madison. Our primary focus is on developing a novel gene therapy for Leber Congenital Amaurosis Type 16 (LCA16), a debilitating retinal disease that leads to severe vision loss in adult and pediatric patients. Our mission is to restore vision and improve the quality of life for affected individuals and their families by harnessing the power of gene delivery technology to target the underlying genetic mutation responsible for the disease. Our team of leading scientists, industry experts and best-in-class partners are committed to rigorous research and clinical development, ensuring that our therapies are safe, effective, and accessible. Through collaboration and innovation, HubbleTx strives to bring hope to those affected by this condition. Together, we aim to illuminate the path to a brighter future for patients battling LCA16. SOURCE Andelyn Biosciences WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Retinitis pigmentosa can eventually lead to complete blindness. Credit: GBJSTOCK via Shutterstock. Gene therapy company Skyline Therapeutics has secured an orphan drug designation from the US Food and Drug Administration (FDA) for its retinitis pigmentosa gene therapy, named SKG1108. There are currently no approved treatments that can halt or reverse photoreceptor degeneration in retinitis pigmentosa, a group of inherited eye disorders that cause progressive loss of vision due to the degeneration of the retina, specifically affecting the photoreceptor cells. This typically begins with night blindness and loss of peripheral vision and can eventually lead to complete blindness. SKG1108 uses a recombinant adeno-associated virus to deliver DNA directly to the retina. This DNA encodes light-sensitive proteins that can help restore vision by creating new photo-sensing cells, which replace the lost rod and cone cells in patients with advanced retinitis pigmentosa. Skyline said the treatment is effective regardless of the specific gene mutation causing the condition. Existing therapies for this rare disease mainly target specific mutant genes that apply only to a small subset of patients. The only approved retinitis pigmentosa therapy on the market is Spark Therapeutics ’ Luxturna (voretigene neparvovec), a retinoid isomerohydrolase activator, indicated for patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. See Also: BR-6002 by Boryung Pharmaceutical for Duodenal Ulcer: Likelihood of Approval BR-6002 by Boryung Pharmaceutical for Gastric Ulcers: Likelihood of Approval One of the main players in this field is US-based Beacon Therapeutics. Its lead asset, AGTC-501 (laruparetigene zovaparvovec) is currently in Phase II/III of development for X-linked retinitis pigmentosa (XLRP) in the VISTA trial (NCT04850118) and has shown good efficacy in previous clinical trials. AGTC-501 is highly anticipated as it has the potential to become the first gene therapy specifically indicated for XLRP, according to a GlobalData analyst . Initial data with AGTC-501 showed an improvement in microperimetry measurements, which was also seen in patients who received the highest dose of the therapy in a Phase II study. In July 2024, Beacon secured $170m in a Series B funding round to advance AGTC-501. China-based Skyline has other ocular disease treatments under its belt, including the gene therapy SKG0106 for neovascular age-related macular degeneration (nAMD). The one-time intravitreally delivered candidate is being evaluated in a Phase I/II clinical trial (NCT05986864) in patients with nAMD. The nAMD market is expected to reach $27.5bn across the seven major markets (US, UK, France, Germany, Italy, Spain, and Japan) by 2031, according to a GlobalData report . GlobalData is the parent company of Pharmaceutical Technology. Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Optimise your cell therapy process: a guide to cell thawing Typically carried out at the point of care, errors in cell therapy thawing could compromise treatment efficacy, leading to significant patient impact as well as high costs and a compromised reputation for the product’s developer. This guide addresses how cell thawing has historically developed into the new techniques used today, along with the physical and biological implications of key metrics and components such as warming rate and ice structure. Also included are reviews of key studies from scientific literature and a consideration of the interactions between cooling and warming rates, as applicable to cell and gene therapies. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy

RPE65 基因突变引起的遗传性视网膜变性 (IRD) ，是一种致盲性眼科遗传疾病，通常在婴幼儿期就开始发病，视网膜和视觉功能逐步退化。几乎所有患者最终都会发展为完全失明，传统治疗方案对此束手无策。 昨晚（7月22日），中国国家药监局药品审评中心（CDE）官网最新公示，上海朗昇生物科技有限公司申报的LX101注射液拟纳入突破性治疗品种。用于治疗RPE65双等位基因突变相关的遗传性视网膜变性（IRD）患者。 LX101 注射液是一款以重组 AAV 基因载体 (rAAV) 为载体的基因疗法物。在特定遗传疾病的治疗策略中，可以减缓甚至停止光感受器退化的过程，保留与中央视觉功能有关的视锥细胞，甚至替换丢失的细胞从而提言患者的视觉功能，是眼科基因治疗的关键策略。 LX101注射液是朗信生物自主研发的一款以rAAV为载体的基因疗法。产品通过对RPE65基因编码序列优化设计，高效表达人源RPE65蛋白，补偿因该基因突变导致的蛋白功能缺失，眼内给药后可有效治疗RPE65双等位基因突变相关的遗传性视网膜变性（IRD）患者。在此前进行的研究者发起的临床研究中，LX101表现出良好的安全性，且已在多位患者中见到视力提高的疗效。 LX101眼用注射液是目前国内递交的首个先天性黑蒙基因治疗新药临床试验申请。先天性黑蒙LCA是一类发生最早、最严重的遗传性视网膜病变, 大多数LCA患者在婴儿期或儿童期开始出现严重视力障碍，并且由于进行性视网膜变性，在30-40岁时彻底失明。LCA目前尚无有效方法治疗，直到近些年来基因治疗领域的快速发展，这种严重视网膜遗传病才有了可用的治疗方法。 伴随全球基因治疗的快速发展，视网膜遗传病治疗领域近年来发生了革命性的变化。2017年12月10日，美国FDA批准了首个眼科基因治疗产品，通过腺相关病毒（AAV）载体，将正常的RPE65基因递送到视网膜细胞，用于治疗先天性黑矇症2型疗效甚佳，但其治疗费用高达85万美元，对于普通家庭来说无疑是“天价”，该药至今也未进入中国市场。 LX101注射液是一款以rAAV为载体的基因疗法，通过对RPE65基因编码序列优化设计，高效表达人源RPE65蛋白，补偿因该基因突变导致的蛋白功能缺失，眼内给药后可有效治疗RPE65双等位基因突变相关的遗传性视网膜变性（IRD）患者。 2021年6月，朗信生物启动了研究者发起的中国首项针对LCA的基因治疗临床研究，评估单次视网膜下腔注射LX101眼用注射液治疗特定类型先天性黑矇的总体安全性和疗效，于6月24日在上海市第一人民医院眼科中心成功完成首例患者治疗。 2021年9月16日，LX101完成了首位LCA患者的视网膜下注射，经过生物工程改造后，LX101带着目的基因片段进入由于基因突变而影响功能的细胞，在其中进行功能修复。 RPE65基因突变引起的遗传性视网膜变性（IRD），是一种典型的致盲性罕见病，常见的IRD包括视网膜色素变性、脉络膜症、Leber遗传性视神经病变(LHON)、Leber先天性黑矇(LCA)、Stargardt病、色盲症(ACHM)和X连锁视网膜劈裂症(XLRS)等，它们的发生是由于一种或多种基因的突变导致视网膜感光细胞死亡而引起。患者婴幼儿期发病，通常经历严重、进行性的视网膜退化和视觉功能恶化，几乎所有患者最终都会进展为完全失明。由于缺乏有效治疗方法，遗传性视网膜病变的致盲率居高不下，直到近些年来基因治疗领域的快速发展，这种严重视网膜遗传病才有了可用的治疗方法。 来源 | 北京药研汇