Ultragenyx Begins Phase 3 Study Of Recombinant Human Beta-Glucuronidase In Sly Syndrome

California based Ultragenyx Pharmaceutical has announced the initiation of a pivotal Phase 3 study of recombinant human beta-glucuronidase (rhGUS, UX003) for the treatment of Sly syndrome (Mucopolysaccharidosis 7 or MPS 7). The company says that it has reached an agreement with the U.S. FDA and EMA on the design of the pivotal trial and has just dosed the first patient in the trial.

"We are pleased to have reached alignment with both the FDA and EMA on our single pivotal study design for this devastating disease," commented Sunil Agarwal, M.D., CMO of Ultragenyx. "This is an important step forward for these patients who have no approved treatment options. It is also an important milestone for Ultragenyx, as it is the start of our first Phase 3 program."

The randomized, placebo-controlled Phase 3 clinical trial is designed to evaluate the safety and efficacy of rhGUS. The study will enroll 12 patients between 5 and 35 years of age, who will be randomized into four different groups. One group of patients will begin rhGUS therapy immediately, while the other three groups will start on placebo first and move to rhGUS at different predefined time points. The patients will be dosed with 4 mg/kg of rhGUS every other week for up to a total of 48 weeks, and all groups will receive at least 24 weeks of rhGUS treatment.

The primary endpoint of the trial is the reduction in urinary glycosaminoglycan excretion after 24 weeks of treatment. The company expects to have results from the Phase 3 study by the first half of 2016.

Ultragenyx says that the European Medicines Agency has agreed that regulatory approval could be possible based on a single successful Phase 3 study using the above endpoint, if accompanied by significant improvement in the most important clinical endpoints (for MPS7, the clinical endpoints are: six-minute walk test, forced expiratory volume, spleen/liver volume).

MPS 7 is a genetic metabolic disorder caused by a deficiency of the lysosomal enzyme beta-glucuronidase, which is necessary for the breakdown of complex carbohydrates called glycosaminoglycans. The condition results in serious problems, such as enlargement of the liver and spleen, airway obstruction, and cardiovascular complications.

Ultragenyx specializes in treatments for rare and inherited disorders. Recently, Ultragenyx nabbed an Orphan Drug designation from the European Commission for its recombinant human monoclonal IgG1 antibody for fibroblast growth factor 23 (KRN23 or UX023) to treat an inherited disease, X-linked hypophosphatemia (XLH).