Ultragenyx’s Genglycos is designed to restore the liver’s ability to break down glycogen and release glucose, potentially reducing patients’ dependence on around-the-clock raw cornstarch therapy.

Ultragenyx Pharmaceutical announced that the US Food and Drug Administration (FDA) has granted accelerated approval for Genglycos (pariglasgene brecaparvovec-opnr), also known as DTX401, for the treatment of adult and paediatric patients aged eight years and older with Glycogen Storage Disease type Ia (GSDIa).

The approval marks Ultragenyx’s first gene therapy approval and introduces a treatment designed to address the underlying cause of GSDIa by restoring the body’s ability to release glucose from glycogen in the liver. According to the company, clinical studies demonstrated that treatment with Genglycos reduced patients’ reliance on raw cornstarch, which is currently a central component of managing the disease.

GSDIa is an ultra-rare genetic metabolic disorder caused by a deficiency of an enzyme required for the liver to release glucose into the bloodstream. This impairment can lead to potentially life-threatening episodes of hypoglycaemia, particularly during fasting or periods of metabolic stress. Patients typically require strict dietary management and frequent consumption of raw cornstarch throughout the day and night to maintain blood glucose levels.

The condition is estimated to affect approximately 1,500–2,500 people in the US and 6,000–8,000 people worldwide across commercially accessible markets.

‘Genglycos’ is intended to restore the normal breakdown of glycogen to produce glucose during periods when the body requires it. Ultragenyx said this mechanism could help reduce the disease burden associated with continuous dietary management and potentially lower the risk of severe hypoglycaemia.

The FDA’s accelerated approval is supported by data from the 48-week, randomised, double-blind, placebo-controlled Phase 3 GlucoGene study, which enrolled 46 participants aged eight years and older. Participants received either DTX401 at a dose of 1.0 × 10¹³ GC/kg or placebo. The study demonstrated a statistically significant reduction in cornstarch requirements among patients receiving DTX401 compared with placebo, with p<0.001.

A total of 44 participants were included in the modified intention-to-treat population used for the Week 48 efficacy analysis. Following the 48-week assessment, eligible participants crossed over to receive the alternate treatment.

As a condition of the accelerated approval, Ultragenyx will conduct additional post-marketing monitoring to generate two years of safety and efficacy data. The programme will include 50 commercially treated patients and 20 control patients who sought treatment but were unable to receive Genglycos because of the presence of anti-AAV8 antibodies.

The monitoring programme is expected to provide additional evidence on reductions in cornstarch requirements, fasting tolerance and other clinical measures in a real-world treatment setting.

Ultragenyx also plans to support patients and caregivers through its UltraCare programme. The programme includes specially trained Gene Therapy Guides who will assist eligible patients with understanding insurance coverage, accessing treatment support and navigating the treatment process.

The company said the approval represents the culmination of decades of scientific and clinical research involving patients, families, investigators and research organisations. The development programme included contributions from GSDIa expert Dr. David Weinstein, Dr. Janice Chou and teams associated with the US National Institutes of Health and Dimension Therapeutics.

According to Ultragenyx, Genglycos represents a significant milestone in the development of gene therapies for rare metabolic disorders, offering a new therapeutic approach for patients and families managing the demanding and potentially life-threatening consequences of GSDIa.