Treatment with DTX401 resulted in a statistically significant reduction in daily cornstarch intake at Week 48 (p Company will host investor call today at 5:00 p.m. ET
May 30, 2024 -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced positive topline results from the Phase 3 GlucoGene study (NCT05139316) evaluating DTX401, an investigational gene therapy for the treatment of patients aged eight years and older with glycogen storage disease type Ia (GSDIa).
The study achieved its primary endpoint, demonstrating that treatment with DTX401 resulted in a statistically significant and clinically meaningful reduction in daily cornstarch intake compared with placebo at Week 48. The mean percent reduction was 41.3% in the DTX401 group (n=20) compared with 10.3% in the placebo group (n=24) at Week 48 (p
“This is an incredible milestone for the DTX401 program. These clinically important and statistically significant results are consistent with our Phase 1/2 findings, and the continued improvement in these treated patients reflects the acquired ability to break down glycogen as a source of endogenous glucose from their treated livers,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “We want to thank the patients, families and treating community for their ongoing participation in this study and their support of progress for the broader GSDIa community.”
The study also successfully met key secondary endpoints of reduction in the number of cornstarch doses per day and maintenance of glucose control at Week 48. Treatment with DTX401 resulted in a mean reduction of 1.1 cornstarch doses per day in the DTX401 treatment group compared with a mean reduction of 0.2 in the placebo group (p=0.0011). Patients in the DTX401 group also showed significant improvement in both frequency and quantity of nighttime cornstarch dosing compared with the placebo group. This blinded study established non-inferiority (p
The Patient Global Impression of Change (PGIC) at Week 48 showed a median score of 2.0 (moderately improved) for the DTX401 treatment group and 1.0 (minimally improved) for the placebo group (p=0.132). Moderately or higher improved PGIC scores correlated with a ≥30% reduction in total daily cornstarch intake indicating that this is a clinically meaningful threshold for patients.
“With these Phase 3 results, the significant reduction in cornstarch intake with continued management of glucose control has the potential to offer meaningful benefit to patients while improving their quality of life on a daily basis,” stated Rebecca Riba-Wolman, M.D., director of the Glycogen Storage Disease Program & Disorders of Hypoglycemia at Connecticut Children’s Medical Center/University of Connecticut Medical School and study investigator. “GSDIa is a disease that never takes a break, where you must constantly think about your own, or your child's, safety and risk of severe low blood sugar and acidosis throughout the day and especially at night. A treatment that can improve these daily concerns for people with GSDIa without significant risks is essential.”
The study demonstrated an acceptable and expected safety profile for DTX401 consistent with Phase 1/2 study results. Anticipated vector-induced hepatic effects were all non-serious and manageable with a prophylactic corticosteroid regimen. No AAV8 class effects of dorsal root ganglion toxicity or thrombotic microangiopathy were observed in the study through Week 48.
Full 48 Week data from the Phase 3 study will be presented at a scientific conference later this year. These results will be discussed with regulatory authorities to support a marketing application in 2025.
Ultragenyx recently presented long-term DTX401 Phase 1/2 data demonstrating durable response, with sustained, clinically meaningful reductions in cornstarch lasting up to 5 years in patients treated with open-label DTX401 as of the data cut-off. All 12 patients in the study have been followed for an average of 4 years and continue to demonstrate improved glucose control, with a mean total daily reduction of cornstarch intake of 72% (p<0.0001) from baseline to their last available timepoint.
The 48-week randomized, double-blind, placebo-controlled study treated 46 patients aged eight years and older with DTX401 (1.0 x 10^13 GC/kg dose measured by ddPCR) or placebo. There were 44 patients in the modified intention-to-treat (mITT) population with efficacy data within the Week 48 analysis period following treatment with DTX401 (n=20) or placebo (n=24). At Week 48, eligible patients crossed over and received the alternate treatment. After crossover, patients will be followed for an additional 96 weeks. After study completion, patients will be offered enrollment into a Disease Monitoring Program (DMP) where they will be followed for at least 10 years post-DTX401 infusion.
GSDIa is a serious inherited glycogen storage disease. It is caused by a defective gene coding for the enzyme G6Pase-α, resulting in the inability to regulate blood sugar (glucose). Hypoglycemia in patients with GSDIa can be life-threatening, while the accumulation of the complex sugar glycogen in certain organs and tissues can impair the ability of these tissues to function normally. If chronically untreated, patients can develop severe lactic acidosis, progress to renal failure, and potentially die in infancy or childhood. There are no approved pharmacologic therapies. An estimated 6,000 patients worldwide are affected by GSDIa.
DTX401 is an investigational AAV8 gene therapy designed to deliver stable expression and activity of G6Pase-α under control of the native promoter to allow the treated liver cells to respond to normal hormonal signals intended to manage glucose, including insulin, glucagon and cortisol. DTX401 is administered as a single intravenous infusion and has been shown in preclinical studies to improve G6Pase-α activity and reduce hepatic glycogen levels, a well-described biomarker of disease progression. DTX401 has been granted orphan drug designation, regenerative medicine advanced therapy (RMAT) designation and Fast Track designation from the U.S. FDA, as well as PRIority MEdicines (PRIME) and orphan drug designation from the European Medicines Agency.
Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease.
The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.
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