Ultragenyx Gets FDA Accelerated Approval for Genglycos Gene Therapy in GSDIa

First Approved Therapy From Ultragenyx Directly Targets the Root Cause of GSDIa

Ultragenyx Pharmaceutical Inc. has received accelerated approval from the U.S. Food and Drug Administration (FDA) for Genglycos (pariglasgene brecaparvovec-opnr), also known as DTX401.

The gene therapy is approved for adults and children aged eight years and older who are living with glycogen storage disease type Ia (GSDIa).

The approval is an important milestone for Ultragenyx because Genglycos is the company's first gene therapy to receive regulatory approval. It also gives people with GSDIa a treatment designed to address the underlying cause of the disease rather than relying only on dietary management.

What Is GSDIa?

GSDIa is an ultra-rare genetic metabolic disorder that affects the body's ability to maintain normal blood glucose levels.

The disease is caused by a deficiency of an enzyme needed to release glucose from the liver into the bloodstream.

When this process does not work properly, patients can develop severe hypoglycaemia, meaning their blood glucose levels can fall dangerously low.

These episodes can become life-threatening and may lead to seizures and other serious complications.

GSDIa is estimated to affect around 1,500 to 2,500 people in the United States and approximately 6,000 to 8,000 people worldwide across commercially accessible markets.

Why Patients Have Relied on Cornstarch

For many people with GSDIa, managing the disease has meant following a strict nutritional routine every day.

Raw cornstarch is commonly used as an oral glucose replacement therapy. Patients may need to consume it regularly throughout the day and night to help maintain blood glucose levels.

This can make everyday life extremely difficult.

Patients and caregivers have to keep track of meals, cornstarch intake and glucose levels. Overnight management can also require constant attention because missing a scheduled dose can increase the risk of hypoglycaemia.

Even when patients follow the regimen carefully, glucose levels can still move up and down significantly.

Genglycos Takes a Different Approach

Genglycos is designed to address the underlying biological problem associated with GSDIa.

The therapy is a gene therapy intended to help restore the normal breakdown of glycogen so the body can produce glucose during periods of fasting or metabolic stress.

In clinical studies, patients treated with DTX401 were able to reduce their reliance on raw cornstarch.

For people who have spent years managing their condition through strict dietary schedules, reducing the need for cornstarch could significantly change daily disease management.

Eric Crombez, chief medical officer at Ultragenyx, said the approval represents the company's commitment to developing a therapy that directly targets the root cause of GSDIa.

Phase 3 Study Supported the FDA Approval

The FDA's accelerated approval was supported by results from the Phase 3 GlucoGene study.

The randomized, double-blind, placebo-controlled study followed patients for 48 weeks.

A total of 46 participants aged eight years and older received either DTX401 at a dose of 1.0 × 10^13 GC/kg or placebo.

The study showed a statistically significant reduction in cornstarch requirements among patients treated with DTX401 compared with placebo.

The difference was highly significant, with a p-value of less than 0.001.

A total of 44 participants were included in the modified intention-to-treat population used for the efficacy analysis during the Week 48 period.

After Week 48, eligible participants crossed over to receive the alternate treatment.

Reduced Cornstarch Use Was a Major Finding

One of the most important findings from the clinical program was the reduction in the amount of cornstarch needed by treated patients.

This matters because cornstarch is not simply an occasional treatment for people with GSDIa. For many patients, it is part of a strict daily routine used to prevent dangerous drops in blood glucose.

Reducing that requirement could make disease management less demanding.

It may also give physicians more flexibility when managing glucose levels and nutritional requirements.

Accelerated Approval Comes With Additional Monitoring

Genglycos received accelerated approval, which means additional clinical evidence will be collected after approval.

As part of the approval, Ultragenyx has agreed to provide two years of safety and efficacy data from commercial treatment.

The company plans to enhance its existing GSDIa Disease Monitoring Program to follow 50 patients receiving commercial treatment and 20 control patients.

The control group will include patients who sought treatment but cannot receive Genglycos because they have anti-AAV8 antibodies.

The post-marketing program will provide additional information on cornstarch requirements, fasting tolerance and other measures in patients receiving treatment in routine clinical practice.

Real-World Monitoring Will Add More Information

Clinical trials are conducted under controlled conditions, while commercial treatment takes place in everyday life.

The monitoring program will allow researchers to collect additional information from patients after Genglycos becomes available.

Patients can monitor their immediate glucose levels, while physicians can make adjustments to cornstarch intake and diet based on those readings.

This could provide a clearer picture of how Genglycos affects long-term disease management outside of a clinical trial setting.

Ultragenyx Prepares Patient Support Through UltraCare

Getting a gene therapy approved is only one part of making it available to patients.

Ultragenyx will provide support through its UltraCare program to help patients and caregivers navigate the treatment process.

The program now includes specially trained UltraCare Gene Therapy Guides.

These guides will help patients understand insurance coverage, access treatment support and navigate questions related to receiving Genglycos.

For a rare disease community, this type of support can be particularly important because treatment centres and specialists may not be available in every location.

A Major Milestone for the GSDIa Community

The approval has been welcomed by physicians and patient advocates who have worked on GSDIa research for decades.

David Weinstein, a leading GSDIa expert, said the approval represents a major step forward after years of scientific work focused on improving safety and quality of life for people living with the disease.

For families, the daily burden of GSDIa can involve strict schedules, overnight monitoring and constant concern about maintaining adequate glucose levels.

David and Wendy Feldman, co-founders and current board members of The Children's Fund for Glycogen Storage Disease Research, described the approval as an important milestone for families who have spent years supporting research into new treatment options.

Nearly Three Decades of Research Behind the Therapy

The development of Genglycos involved contributions from researchers, physicians, patients and several organizations over many years.

Ultragenyx acknowledged the patients and families who participated in clinical studies, as well as clinical investigators who supported the program.

The company also recognized David Weinstein for his scientific and clinical leadership, along with Dr. Janice Chou for her early work at the National Institutes of Health.

The team from Dimension Therapeutics was also recognized for its contribution to the development program.

What the Approval Means for Ultragenyx

Genglycos is the first gene therapy approved by the FDA for Ultragenyx.

The approval gives the company an opportunity to bring its gene therapy capabilities into commercial use while expanding its presence in rare metabolic diseases.

For the GSDIa community, the treatment provides a new approach to managing a disease that has traditionally required intensive nutritional intervention.

The next stage will involve making Genglycos available to eligible patients while continuing to collect safety and efficacy data through the post-marketing monitoring program.