Phase 1/2 MPS I Gene Therapy Trial Finishes Dosing


REGENXBIO expects to provide updated interim data from the trial in the first half of next year.

The phase 1/2 clinical trial (NCT03580083) of REGENXBIO’s RGX-111, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat severe mucopolysaccharidosis Type I (MPS I), has completed dosing of all 8 enrolled patients.1

RGX-111 is intended to deliver a functional copy of α-l-iduronidase (IDUA), the disease-targeted gene, via the company’s the NAV AAV9 vector. The therapy is administered directly to patients’ central nervous systems (CNS). In the trial, 2 of the 8 patients received the lower dose of 1.0x1010 genome copies per gram (GC/g) of brain mass, and the other 6 patients received the higher dose of 5.0x1010 GC/g of brain mass. Early safety and efficacy data from the trial was presented at the 18th Annual WORLDSymposium in February of this year. REGENXBIO expects to provide updated interim data from the trial in the first half of next year. One additional patient has been treated with RGX-111 outside of the clinical trial via a single-patient investigational new drug application; this patient also received the lower dose. 

"We have made great progress this year advancing our pipeline of neurodegenerative disease programs, and completing the dosing in this MPS I trial is another important clinical milestone as we continue to develop potential 1-time gene therapies for patients," Steve Pakola, MD, chief medical officer, REGENXBIO, said in a statement regarding the news.1 "Earlier, at this year's WORLDSymposium meeting, we presented data on biomarker and neurodevelopmental assessments that indicated an encouraging CNS profile in patients dosed with RGX-111. We intend to advance the program for RGX-111 with the aim of providing a much-needed new treatment option for the MPS I community as quickly as possible."

The global, open-label, multicenter clinical trial was open to patients 4 months and older with documented evidence of CNS involvement due to MPS I or a documented diagnosis of severe MPS I. Patients who previously received hematopoietic stem cell transplant were eligible with the approval of the principal investigator, medical monitor, and sponsor. Patients with contraindications for intracisternal and intracerebroventricular injection or lumbar puncture; contraindications for immunosuppressive therapy; or a neurocognitive deficit not attributable to MPS I or a diagnosis of a neuropsychiatric condition were excluded from the study. Patients with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3× the upper limit of normal (ULN) or total bilirubin greater than 1.5× ULN at screening were also excluded (unless the patient had a previously known history of Gilbert syndrome and a fractionated bilirubin that showed conjugated bilirubin less than 35% of total bilirubin) were also excluded, as were patients who had ever previously received intrathecal (IT) laronidase and experienced a significant adverse event (AE) considered related to IT administration, patients who had ever previously received intravenous (IV) laronidase and experienced a significant AE considered related to IV administration, and patients who had received any investigational product within 30 days of Day 1 or 5 half-lives before signing of the Informed Consent Form.

The study’s primary end point is the number of participants who experience treatment-related AEs and serious AEs in a 24 week timeframe. Secondary end points include the number of participants who experience treatment-related AEs within a 104 week timeframe; changes in neurodevelopmental parameters measured by the Wechsler Abbreviated Scale of Intelligence, 2nd Edition (WASI-II), the Bayley Scale of Infant and Toddler Development, Third Edition, and the Wechsler Preschool and Primary Scales of Intelligence, Fourth Edition; the change from baseline in neurodevelopmental parameters of attention as measured by the Tests of Variables of Attention, Version 9, if able to complete the WASI-II; the change in adaptive behavior; and measures of vector shedding. Caregiver reported outcomes will also be evaluated. The trial is being carried out at sites in the US and Brazil. REGENXBIO has announced plans to communicate with regulatory agencies frequently, and the company also expects to begin manufacturing the gene therapy product at commercial-scale in the first half of next year for the purpose of supporting continued development. RGX-111 has previously been granted orphan drug designation, rare pediatric disease designation, and fast track designation by the FDA.

"Our '5x'25' strategy is to have 5 gene therapies either on the market or in late-stage development by 2025,” Kenneth T. Mills, president and chief executive officer, REGENXBIO, added to the statement.1 “Earlier this year, we announced that the pivotal program for RGX-121 is active and enrolling patients, making this our second internal program to enter late-stage development. RGX-111 is our next most-advanced clinical candidate in our neurodegenerative disease pipeline and over 30 children with severe MPS I and MPS II have been dosed in our trials using the NAV AAV9 vector. I would like to express my deep gratitude to our employees and clinical partners, as well as patients and their families in the MPS community, for their ongoing commitment and support in the development of both RGX-111 and RGX-121."

1. REGENXBIO announces completion of dosing in the phase I/II trial of RGX-111 for the treatment of severe MPS I. News release. REGENXBIO Inc. 
2. Wang R, Ficicioglu C, Giugliani R, et al. RGX-111 gene therapy for the treatment of severe mucopolysaccharidosis type I (MPS I): Interim analysis of data from the first in-human study. Presented at: 18th Annual WORLDSymposium, February 7-11, 2022; San Diego, CA.
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