Ultragenyx wins FDA approval for first treatment targeting root cause of GSDIa

US biopharma Ultragenyx has secured its first gene therapy approval, with the FDA clearing GENGLYCOS as the first treatment designed to address the underlying cause of the ultra-rare metabolic disorder, glycogen storage disease type Ia (GSDIa).

GSDIa is caused by a deficiency in glucose-6-phosphatase, an enzyme that causes the liver to release glucose into the bloodstream during fasting. Without it, patients can experience potentially life-threatening hypoglycaemia and must maintain strict dietary regimens, including frequent doses of raw cornstarch to keep blood sugar levels stable.

GENGLYCOS is designed to address the root cause of the genetic defect. The one-time treatment uses an AAV8 vector to deliver a functional copy of the affected gene to the patient’s liver cells, with the aim of restoring the liver’s ability to regulate glucose.

“For families affected by GSDIa, every day revolves around strict schedules, overnight vigilance, and the constant worry that a missed meal or dose of cornstarch could trigger life-threatening hypoglycaemia,” said David and Wendy Feldman, co-founders and current Board members at The Children’s Fund for Glycogen Storage Disease Research. “This approval is an incredibly meaningful milestone for a community that has spent decades hoping, advocating, and helping advance the research for new treatment options that could ease the burdens of this disease.”

The approval was supported by results from Ultragenyx’s Phase 3 GlucoGene trial, which enrolled 46 patients aged eight and older. After 48 weeks, patients treated with DTX401 required significantly less cornstarch than those receiving placebo, meeting the study’s primary endpoint with a p-value below 0.001.

The data helped Ultragenyx secure an accelerated approval, which means the company will have to generate additional evidence after launch. Under an agreement with the FDA, it will follow 50 commercially treated patients for two years, alongside 20 patients who cannot receive GENGLYCOS because of pre-existing antibodies against the AAV8 vector.

“The approval of GENGLYCOS fulfils our commitment to provide the first therapy that directly targets the root cause of GSDIa. The reduced reliance on cornstarch, experienced by patients in our clinical studies, demonstrates this gene therapy’s ability to establish the normal breakdown of glycogen to produce glucose during fasting or episodes of metabolic stress. This ability to regulate glucose has alleviated the disease burden and has the potential to mitigate the risk of severe or life-threatening hypoglycaemia for these patients,” said Eric Crombez, MD, chief medical officer at Ultragenyx. “As our first gene therapy approval, GENGLYCOS represents an important achievement for our company and the realisation of the promise of a powerful new tool to deliver transformative medicines for people living with rare diseases.”

The post-marketing programme will assess cornstarch use, fasting tolerance, and other measures in a real-world setting. Moreover, Ultragenyx plans to follow patients from both its clinical studies and commercial programme for up to 10 years.

The company will make GENGLYCOS available through a network of Qualified Treatment Centres and has expanded its UltraCare patient support programme to help patients and caregivers navigate insurance coverage and treatment logistics.

Manufacturing will take place at Ultragenyx’s gene therapy facility in Bedford, Massachusetts, which the company says will support its ability to scale production.

The FDA approval also comes with a Priority Review Voucher, giving Ultragenyx a potentially valuable regulatory asset that it can use for a future product or sell to another drugmaker.