IDUA

The partnership centres on two of Regenxbio’s gene therapies, RGX-121 and RGX-111. Credit: Jinda Noipho via Getty Images. Regenxbio has entered into a strategic collaboration worth $810m with Japan-based Nippon Shinyaku to advance gene therapies targeting the rare metabolic disorder mucopolysaccharidosis (MPS). Under the terms of the deal, which centres on two of Regenxbio’s assets – RGX-121 and RGX-111 – Regenxbio will receive $110m upfront and is eligible for up to $700m in development, regulatory, and sales milestones. Nippon Shinyaku gains rights to co-develop and commercialise the therapies in specified markets. MPS includes a group of rare, inherited metabolic disorders caused by the absence or malfunctioning of specific enzymes required to break down glycosaminoglycans (GAGs), complex sugar molecules. The accumulation of GAGs leads to progressive tissue and organ damage, developmental delays, and in severe cases, early mortality. The most advanced candidate in the partnership, RGX-121 (clemidsogene lanparvovec), targets Hunter syndrome, also known as MPS II, a condition caused by a mutation in the iduronate-2-sulfatase (IDS) gene. RGX-121 is designed to deliver a functional copy of the IDS gene, addressing the underlying cause of the disease. Symptoms of Hunter syndrome include cognitive impairment, skeletal abnormalities, and organ enlargement. In September 2024, Regenxbio reported positive results from the Phase II/III CAMPSIITE trial (NCT03566043) of RGX-121, showing an 85% median reduction of cerebrospinal fluid (CSF) levels of heparan sulphate (HS) D2S6, a key biomarker linked to disease activity. In June 2024, the company announced progress with the US Food and Drug Administration (FDA) to pursue an accelerated approval pathway, with a rolling biologics license application (BLA) submission underway. An accelerated approval decision is expected in 2025, and Regenxbio retains rights to a priority review voucher (PRV) for RGX-121. The second asset, RGX-111, is being developed for mucopolysaccharidosis type I (MPS I), caused by mutations in the α-l-iduronidase (IDUA) gene. The gene therapy aims to deliver a functional copy of the IDUA gene directly to the central nervous system (CNS), potentially slowing cognitive decline and other symptoms. Interim data from an ongoing Phase I/II trial (NCT03580083) has shown a favourable safety profile and promising biomarker data indicative of CNS activity. Regenxbio continues to advance its broader pipeline of gene therapies for rare diseases. The company’s wet age-related macular degeneration (wAMD) programme, ABBV-RGX-314, partnered with AbbVie, is being evaluated in two pivotal trials , ATMOSPHERE (NCT04704921) and ASCENT (NCT05407636). Plans are also underway for a Phase III study of the therapy in diabetic retinopathy. Additionally, the company is progressing RGX-202, a gene therapy for Duchenne muscular dystrophy. Following positive data from a Phase I/II trial, Regenxbio has aligned with the FDA on an accelerated approval pathway, with a BLA submission anticipated in 2026. 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

RegenXBio began its rolling approval submission to the FDA for accelerated approval of RGX-121 in the third quarter of last year.\n With an FDA approval submission for RegenXBio’s Hunter syndrome gene therapy already underway, the biopharma has now found a commercialization partner for both the U.S. and Asian markets.That partner, Japan’s Nippon Shinyaku, is handing over $110 million upfront to lead on the commercialization of two gene therapies—RGX-121 for Hunter syndrome and RGX-111 for Hurler syndrome. RegenXBio will also be in line for up to $40 million in development and regulatory milestones and $660 million in sales milestones as well as double-digit royalties on net sales.RegenXBio began its rolling submission to the FDA for accelerated approval of RGX-121 in the third quarter of last year with the expectation that the submission be completed in the first quarter of 2025. With a regulatory decision expected before the end of this year, RGX-121 could become the first gene therapy approved for Hunter syndrome.Also known as mucopolysaccharidosis type II, Hunter syndrome is a rare inherited disorder in which the body is unable to break down sugar molecules. This leads to buildup in the organs and can cause damage over time that affects patients’ physical and mental abilities. RGX-111, which is being developed for a similar inherited disorder called Hurler syndrome, is further back in development. RegenXBio said the gene therapy has demonstrated “very promising results” in a phase 1/2 study. While RGX-121 is designed to deliver the IDS gene within cells in the central nervous systems of patients, RGX-111 uses a AAV9 vector to deliver the IDUA gene.“This partnership with Nippon Shinyaku is exciting in that it maximizes our collective strengths and enables access of two potentially transformational medicines to key markets,” RegenXBio CEO Curran Simpson said in the release. “The structure of the agreement allows us to leverage our expertise in gene therapy manufacturing while also capturing milestones and a meaningful share of future product revenues.”Under the agreement, Nippon Shinyaku will commercialize both gene therapies in the U.S. and Asia, while RegenXBio will retain control of the further clinical development of the candidates. RegenXBio is also keeping hold of the proceeds from the priority review voucher it may receive once RGX-111 gets approved.

▎药明康德内容团队编辑 日前，Immusoft公布首位接受其工程化B细胞疗法ISP-001治疗的1型黏多糖贮积症（MPS I）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。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）。 MPS I是一种罕见且致命的儿童遗传病，会影响身体产生α-L-艾杜糖苷酸酶（IDUA，一种有助于分解细胞内长链糖的必需酶）的能力。当糖链无法分解时，它们会在细胞中积聚并造成渐进性损伤，这种积聚会发生在包括大脑的组织中。在最严重的情况下，受影响的儿童在确诊后很少生存超过十年。 ISP-001是一款经过基因工程改造的自体B细胞疗法，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，让经过改造的B细胞生成治疗性蛋白。这些细胞输注回患者体内可成为患者体内的蛋白“生产工厂”，可以长期生产大量治疗性蛋白，从而改善患者症状。 日前公布的临床试验结果显示，首位接受ISP-001治疗的患者在接受治疗3-8个月后，尿液中的多糖疾病生物标志物水平降低到正常范围内。这名患者脑脊液中的硫酸乙酰肝素（HS）水平在接受治疗6个月时降低25%。这是FDA认可的一个与MPS I疾病活动相关的替代终点。 生物标志物之外，这名患者的6分钟行走检测表现提高30%，并且肩部活动范围在6个月时得到改善。关节僵硬是MPS I的症状之一。在接受治疗8个月后，该患者停止使用标准ERT疗法，随后的一个月里，6分钟行走检测表现仍然获得改善，不过幅度比6个月时有所下降，肩部活动范围的改善得到维持。 ISP-001的耐受性良好。截至2024年9月19日，尚未报告任何不良事件。 ▲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] 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 [2] First patient who received engineered B cell therapy sees early promise for MPS I. Retrieved October 15, 2024, from https://endpts.com/first-patient-who-received-engineered-b-cell-therapy-sees-early-promise-for-mps-i/ 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