FDA grants priority review to gene therapy for Sanfilippo type A
Decision expected by Aug. 18 on Ultragenyx's UX111 approval request
The U.S. Food and Drug Administration (FDA) has accepted Ultragenyx Pharmaceutical‘s application seeking approval of UX111, a gene therapy for Sanfilippo syndrome type A, and granted it priority review, which will speed the agency’s decision.
By being granted priority review, the biologics license application (BLA) will be reviewed in six months instead of the 10 months for standard review. A decision from the FDA on Ultragenyx’s application is now expected by Aug. 18.
“Acceptance of the UX111 BLA brings us closer to being able to provide a first-ever treatment for Sanfilippo syndrome type A,” Emil D. Kakkis, MD, PhD, president and CEO of Ultragenyx, said in a company press release, adding that, “if [the] application is successful, we’re prepared to launch this therapy for patients and their families.”
The one-time gene therapy is designed to ease disease symptoms in Sanfilippo type A patients.
UX111 designed to ease symptoms in Sanfilippo type A patients
In all forms of Sanfilippo, the sugar molecule heparan sulfate, known as HS, builds up to toxic levels and causes damage to brain cells. The FDA agreed last year that HS reductions in the cerebrospinal fluid — known as the CSF, it’s the fluid that surrounds the brain and spinal cord — could serve as a surrogate endpoint when seeking accelerated approval for UX111. Surrogate endpoints are deemed to predict a treatment’s clinical benefit.
Sanfilippo type A is caused by a defective SGSH gene, which causes a deficiency in an enzyme of the same name. The therapy, originally developed by Abeona Therapeutics and later acquired by Ultragenyx, is meant to introduce a functional copy of the SGSH gene into patients’ cells, enabling the production of a working SGSH enzyme. The therapy is delivered via a viral vector by intravenous, or into-the-vein, infusion.
By restoring the breakdown of HS, the therapy is anticipated to slow neurodegeneration and alleviate the symptoms of this Sanfilippo type.
The application seeking UX111’s approval is backed by findings from the ongoing Phase 1/2/3 Transpher A clinical trial (NCT02716246). The study, expected to run through 2027, is still recruiting patients at two sites in Spain.
Our UX111 program could serve as a step [toward] advancing drug development across multiple metabolic diseases of the brain.
Thus far in Transpher A, 28 children with Sanfilippo type A were treated with UX111 and will be monitored for up to two years. After the study’s completion, participants will have the option to join a Phase 3 extension study (NCT04360265), where they will be followed for a minimum of five years.
Ultragenyx released data from 17 participants who received the highest dose of UX111 and had a cognitive development quotient, or DQ, of at least 60 at study entry. The DQ is a measure of a child’s developmental progress compared with age-matched reference values, with a score of 100 being about average.
In the trial, HS levels were shown to drop rapidly within the first month of treatment for all participants, with these reductions being maintained over a mean period of nearly 2.5 years.
Further, all but one participant showed either stable or improved cognitive function. Importantly, the researchers noted, most improvements were seen in children at an age when cognitive decline is usually expected in Sanfilippo type A. HS levels were significantly associated with better cognitive scores.
UX111 was well tolerated overall, with the most common side effect being elevated liver enzymes, which were mostly mild to moderate in severity.
According to Kakkis, Ultragenyx has “[reached] alignment with the [FDA] on a path forward for accelerated approval” for the gene therapy.
“Our UX111 program could serve as a step [toward] advancing drug development across multiple metabolic diseases of the brain,” Kakkis said.
The FDA has previously granted UX111 both rare pediatric disease and orphan drug designations, Ultragenyx noted. Those designations are awarded to therapies developed for rare diseases, defined as those affecting fewer than 200,000 people in the U.S. The gene therapy has also been put on fast track status by the FDA, and been named a regenerative medicine advanced therapy, the company noted. Regulators in the European Union have also granted UX111 an orphan medicinal product designation. Such designations come with varying incentives to speed a treatment’s development, which can include a period of market exclusivity should the therapy ultimately be approved.
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