Ultragenyx Pharmaceutical (RARE) has earned its first FDA approval in gene therapy, landing an accelerated green light for its treatment targeting glycogen storage disease type Ia.
The FDA approved pariglasgene brecaparvovec-opnr, previously known as DTX401, which will now reach patients under the brand name Genglycos.
The accelerated approval covers adults and children over the age of 8 years living with GSDIa, an ultrarare genetic disorder caused by a deficiency of the enzyme G6PC.
The G6PC enzyme is needed to release glucose from the liver into the bloodstream, and without it patients face potentially life-threatening hypoglycemia episodes and other serious complications.
Ultragenyx estimates there are between 1,500 and 2,500 people living with GSDIa in the United States, out of a global patient population of 6,000 to 8,000 within commercially accessible geographies.
The approval marks Ultragenyx’s fifth FDA green light overall and also nets the company a valuable priority review voucher alongside the clearance.
Just over a year ago, the Novato, California-based company suffered a setback when the FDA rejected its gene therapy candidate UX111 for Sanfilippo syndrome type A on manufacturing grounds.
In that complete response letter, the FDA requested additional information and improvements tied to manufacturing-related issues and observations from production facility inspections, with the core clinical data not in question.
Ultragenyx pressed forward regardless, and is presently awaiting a September 19 target decision date on UX111 from an FDA whose upper ranks look very different now than they did last year.
Genglycos proved its merit in Ultragenyx’s late-stage GlucoGene study, which pitted the treatment against placebo over 48 weeks and focused on patients’ ability to reduce daily cornstarch intake.
Treating GSDIa demands rigorous nutritional management, requiring an around-the-clock regimen of raw cornstarch as an oral glucose replacement therapy, according to Ultragenyx.
Glucose control with cornstarch is a crude tool at best, with patients often experiencing large swings in blood sugar and spending much of their day with elevated glucose levels to avoid dangerous lows.
“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., Ultragenyx’s chief medical officer.
“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,” Crombez added in the company’s approval announcement.
In the phase 3 study, Genglycos helped patients achieve a mean 31% reduction from baseline in daily cornstarch intake versus placebo, satisfying the trial’s primary endpoint.
As a one-time AAV8 gene therapy, Genglycos is designed to deliver a functional G6PC gene directly to the liver to restore stable blood sugar regulation during fasting.
As a post-approval commitment, Ultragenyx has pledged to furnish the FDA with two years of safety and efficacy data from open-label commercial treatment of 50 patients and 20 control patients.
The company noted the control arm will comprise patients who sought commercial treatment but cannot receive Genglycos due to the presence of anti-AAV8 antibodies.
Ultragenyx said it will produce the therapy entirely at its gene therapy production facility in Bedford, Massachusetts, which it expects to streamline access for US patients.
The company will provide access support via its UltraCare programme, which now includes specially trained gene therapy guides to assist patients in navigating their route to treatment.