The accelerated greenlight for Ultragenyx’s gene therapy for glycogen storage disease has raised analyst expectations for approval of UX111, which the FDA rejected last summer and is currently reviewing for a second time. A decision is expected by mid-September.
Ultragenyx has received accelerated FDA approval for its gene therapy DTX401 in glycogen storage disease type Ia, raising hopes that the biotech can deliver back-to-back authorizations. The company’s previously rejected Sanfilippo gene therapy is set to receive a decision by Sept. 19.
The approval, which Ultragenyx announced Wednesday, is an “important regulatory win that de-risks UX111,” TD Cowen analysts said in an investor note Wednesday.
Glycogen storage disease type Ia (GSDIa) is a rare disease caused by the accumulation of the complex sugar in cells. As glycogen builds up in the liver, kidneys and small intestines, it impairs cell function and can lead to seizures, developmental delays and cognitive impairment. Patients consume raw cornstarch to manage the condition.
DTX401, which Ultragenyx will sell as Genglycos, is indicated to reduce daily cornstarch intake as an adjunct to nutritional management in adults and children aged eight years and older. The therapy uses an adeno-associated virus vector to deliver the gene for the G6Pase enzyme at the root of GSDIa. In a Phase 3 trial, patients in the DTX401 arm required less cornstarch than their peers in the placebo group.
Accelerated approval of Genglycos ahead of the Aug. 23 deadline “is a key milestone, as it marks the first gene therapy approval for the company (validating years of investment in this platform),” TD Cowen analysts said in an Aug. 19 note to investors.
The terms of the accelerated approval require Ultragenyx to provide two years of safety and efficacy data from open-label commercial treatment of 50 patients and 20 control patients. The control arm will enroll patients who sought commercial treatment but have anti-AAV8 antibodies that preclude Genglycos use.
With this approval in hand, attention now shifts to Ultragenyx’s Sanfilippo syndrome type A gene therapy UX111, which the biotech refiled in February and the FDA accepted for review in April.
The complete response letter issued last July reflected the FDA’s questions about the chemistry, manufacturing and controls module and observations its inspectors made during a facility inspection. TD Cowen analysts framed the Genglycos authorization as a good omen for UX111 because the therapies use the same fill/finish facility, adding that UX111’s approval is now “likely.”
Genglycos’ approval is also a boon to Ultragenyx’s business thanks to a rare pediatric disease priority review voucher (PRV) the company has now received. PRVs typically sell for more than $100 million.
Analysts were uncertain if DTX401 would win approval in the run-up to the FDA’s decision. Guggenheim Securities in an Aug. 4 note to investors gave DTX401 a 70% probability of success. In a May 5 note, TD Cowen analysts said “FDA volatility with gene therapy approvals” led them to exclude the PRV for DTX401 from their models of Ultragenyx’s business.
The biotech should receive another PRV if the FDA approves UX111. Ultragenyx’s path to profitability in 2027 “relies heavily” on PRV sales, TD Cowen said in May. The FDA decisions for DTX401 and UX111 are part of a key period for Ultragenyx, which is also scheduled to report Phase 3 data on GTX-102 in Angelman syndrome this year.
