FDA Grants Accelerated Approval to Ultragenyx's GENGLYCOS, First Gene Therapy for Glycogen Storage Disease Type Ia
核心洞察
The U.S. FDA granted accelerated approval to GENGLYCOS (搜索) (pariglasgene brecaparvovec-opnr (搜索)), the first gene therapy for glycogen storage disease type Ia (搜索) (GSDIa), in patients aged eight years and older.
Approval was based on the Phase 3 GlucoGene study, which showed a significant reduction in cornstarch requirements in treated patients (p<0.001).
GENGLYCOS (搜索) is an AAV8-based gene therapy that directly targets the G6PC (搜索) gene defect underlying GSDIa, reducing reliance on burdensome around-the-clock cornstarch regimens.
Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) announced on August 19, 2026, that the U.S. Food and Drug Administration (FDA) granted accelerated approval for GENGLYCOS (搜索)™ (pariglasgene brecaparvovec-opnr (搜索)), also known as DTX401, in adult and pediatric patients eight years and older with glycogen storage disease type Ia (搜索) (GSDIa). The approval marks the first gene therapy approval, and fifth FDA approval overall, for the company, and provides the first-ever therapeutic option designed to reduce the burden of care associated with this ultra-rare metabolic disorder.
"The approval of GENGLYCOS (搜索) fulfills 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," said Eric Crombez, M.D., chief medical officer at Ultragenyx. "This ability to regulate glucose has alleviated the disease burden and has the potential to mitigate the risk of severe or life-threatening hypoglycemia for these patients."
Disease Background and Unmet Need
GSDIa is an ultra-rare, serious, and life-threatening disease caused by an inborn error of carbohydrate metabolism resulting from pathogenic variants of the G6PC (搜索) gene, which encodes G6Pase (搜索), an enzyme critical for the release of glucose from glycogen and other metabolic sources. Deficiency of G6Pase activity produces severe hypoglycemia during fasting periods between meals and overnight, along with excess hepatic glycogen storage, metabolic derangements, and other disease-related complications.
Current management relies on a burdensome, around-the-clock regimen of raw cornstarch intake as an oral glucose replacement therapy. Glucose control with cornstarch is described as crude, with large swings in glucose, leaving patients spending a large fraction of their day significantly hyperglycemic to avoid hypoglycemic episodes. GSDIa affects an estimated 1,500–2,500 patients in the U.S. and 6,000–8,000 worldwide within commercially accessible geographies.
"Day-to-day management of GSDIa requires a relentless regimen of raw cornstarch and strict dietary management that can be extraordinarily demanding for patients and families. Even with meticulous adherence to this regimen, patients must be perfect. Any missed cornstarch puts patients at risk of severe hypoglycemia, seizures, and even death," said David Weinstein, M.D., MMSc, one of the world's leading GSDIa experts.
Clinical Evidence Supporting Approval
The approval is based on positive data from the 48-week randomized, double-blind, placebo-controlled Phase 3 GlucoGene study, which treated 46 participants aged eight years and older with DTX401 (1.0 x 10^13 GC/kg dose) or placebo. The study demonstrated a reduction in cornstarch requirements in the treated group (p<0.001). A total of 44 participants in the modified intention-to-treat (mITT) population provided efficacy data within the Week 48 analysis period following treatment with DTX401 (n=20) or placebo (n=24). At Week 48, eligible participants crossed over and received the alternate treatment, with follow-up analyses conducted at Week 96 and Week 144.
The indication is approved under accelerated approval based on reduction in daily cornstarch intake, and continued approval may be contingent upon verification of clinical benefit in confirmatory trial(s).
Post-Marketing Requirements
As part of the accelerated approval, Ultragenyx has agreed to provide two years of safety and efficacy clinical data from open-label commercial treatment of 50 patients and 20 control patients through enhancement of its existing GSDIa Disease Monitoring Program (DMP). The control group will consist of patients who sought commercial treatment but cannot be treated with GENGLYCOS (搜索) due to the presence of anti-AAV8 antibodies. The study will provide additional data to support reduction in cornstarch clinical burden, fasting tolerance, and other measures in a post-marketing setting. The DMP will also evaluate previously treated clinical trial participants as well as new commercial patients for a total of 10 years.
Safety Profile
GENGLYCOS (搜索) is contraindicated in patients with known severe hepatic fibrosis or cirrhosis. The prescribing information details warnings and precautions for hypersensitivity and infusion reactions, hepatotoxicity, adrenal insufficiency, and a theoretical risk of tumorigenicity due to AAV vector DNA integration.
Seven serious adverse events were observed in the Primary Efficacy Analysis Period (PEAP) of Study 1 (Weeks 1–48), including anaphylaxis/infusion reaction (2), adrenal insufficiency (2), high lactate level (2), and hypoglycemia (1). The most common adverse reactions during the PEAP (occurring in ≥10% of patients) with higher frequency in GENGLYCOS (搜索) compared to placebo were ALT/AST enzyme elevation (71%), nausea (38%), hypertriglyceridemia (29%), headache (24%), adrenal insufficiency (24%), constipation (19%), acne/dermatitis acneiform (19%), hyperglycemia (14%), Cushingoid features (14%), and anaphylaxis (10%).
Access and Manufacturing
Ultragenyx will support patient access through its UltraCare® program, which now includes specially trained UltraCare® Gene Therapy Guides to help navigate insurance coverage and treatment support. GENGLYCOS (搜索) will be available through a national network of Qualified Treatment Centers (QTCs) with specialized expertise in administering gene therapy. The therapy is manufactured entirely at Ultragenyx's Gene Therapy Manufacturing Facility (GTMF) in Bedford, Mass.
"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 hypoglycemia," 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."