Ultragenyx up on XLH drug's phase 3 success

XLH is a genetic disease in which phosphate wasting causes rickets (top). (National Museum of Health and Medicine)

Ultragenyx Pharmaceuticals chalked up another win for its rare bone disease drug, burosumab, keeping it on track for a U.S. regulatory filing. 

The California-based biotech unveiled positive 48-week data from its phase 3 study of burosumab in adults with X-linked hypophosphatemia (XLH), a rare genetic disease that causes rickets. Ultragenyx's shares were up more than 4% in premarket trading, while Jefferies analysts said in a note that the drug's approval was "likely." Its PDUFA date is April 17, 2018. 

Typically diagnosed in childhood, XLH is caused by phosphate wasting in the kidneys. Low phosphate levels in the blood lead to rickets—or soft, weak bones—and short stature, bent legs and bone and dental pain. While there are a handful of treatments for children, including growth hormone and corrective surgery, treatment for adults focuses on managing pain, according to the NIH

The news comes eight months after Ultragenyx announced encouraging 24-week data from the trial. 

“This longer term data on symptom improvement and fracture healing support burosumab’s potential value in treating serious disease symptoms and promoting bone healing in adult patients with XLH,” said Ultragenyx CEO Emil Kakkis, M.D., in a statement. “The continued clinical improvements in patients and the new data demonstrating a significant decrease in pain medication use after treatment with burosumab provide further support for the potential value in the treatment of adults with XLH.” 

The study involved 134 patients, half of whom received a 1mg/kg dose of burosumab every four weeks for 24 weeks. The other half received a placebo. 

At 24 weeks, the investigators found the drug outperformed placebo in normalizing serum phosphorus levels, as well as in improving clinical symptoms of XLH, including stiffness and physical function. 

After the 24-week mark, the placebo patients were also put on burosumab. During the ensuing 24 weeks of treatment, 89% of the patients who had crossed from placebo to burosumab maintained serum phosphorus levels above the lower bound of normal, compared to 84% of those receiving the drug from the start. 

Between weeks 24 and 48, the crossover patients showed improvement in stiffness, physical function and pain scores, comparable to the gains seen in those treated with burosumab from the beginning. And to top it all off, the crossover patients' fracture healing rate improved from 8% in the first 24 week-period to 35% in the second 24 weeks, which is consistent with the rate observed in the other arm in the first treatment period. 

"We look forward to progressing our discussions with the regulatory bodies in Europe and the US,” said Dr. Tom Stratford, President and CEO of Kyowa Kirin International, with which Ultragenyx is developing burosumab. 

The drug is currently in a second phase 3 trial investigating its effect on osteomalacia, or bone softening, and is also being tested in pediatric patients. 

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