Mucopolysaccharidosis I

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

Nippon Shinyaku has paid $110 million upfront for the rights to sell two of Regenxbio’s gene therapies for mucopolysaccharidosis in the US and Asia. The deal also provides for potential milestone fees of up to $700 million — $40 million for development and regulatory goals and $660 million in sales milestones. Regenxbio would also get double-digit royalties on net sales in the US and Asia, according to a Tuesday release . The assets in question are RGX-121, a therapy for mucopolysaccharidosis (MPS) II, also known as Hunter syndrome, and RGX-111, intended for MPS I or Hurler syndrome. MPS type I and II patients cannot produce particular enzymes that break down large sugar molecules. The sugars accumulate in patients’ tissues, causing various physiological and neurological symptoms. Regenxbio’s gene therapies are administered to the cerebrospinal fluid and deliver genes encoding the missing enzymes. RGX-121 achieved significant cuts in levels of a disease biomarker called heparan sulfate according to data released in February 2024 . In November, Regenxbio said that a BLA submission for RGX-121 via the accelerated approval pathway was expected to be completed in Q1 2025. If the agency gives a green light, RGX-121 could become the first gene therapy for MPS II, the companies say. Other companies are also seeking accelerated approval for forms of MPS based on biomarker findings. Denali Therapeutics is conducting a Phase 2/3 trial of its Hunter syndrome candidate DNL310, and Ultragenyx has submitted a BLA for its gene therapy for Sanfilippo syndrome type A — both using heparan sulfate. RGX-111 is earlier in development. It was well tolerated in eight patients in a Phase 1/2 study, according to data Regenxbio released two years ago. It also showed a decrease in levels of a disease biomarker in the CSF of “the majority of patients.” Regenxbio will continue to lead the clinical development of the assets, and the US biotech retains all rights to the priority review voucher it will receive if RGX-121 gains approval. It will also take charge of manufacturing.

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.