Ultragenyx on course for rare disease XLH drug filing after phase 3 win

CEO says study shows patients have "turned the corner from a lifetime of decline."

Ultragenyx Pharmaceuticals needed a win for its lead drug burosumab after a midstage pipeline failure and delivered with a good set of phase 3 results.

The biotech said the data keep burosumab on course for an FDA filing for the rare bone disease X-linked hypophosphatemia (XLH) later this year, and helps the company shrug off the earlier phase 2 miss for G1DS candidate triheptanoin, which prompted a run on its shares. Ultragenyx has already filed a conditional marketing application for the drug in Europe.

With the new data, analysts at Leerink now give burosumab (also known as KRN23) a 90% chance of FDA approval, predicting peak sales of the drug could reach around $1 billion from 2025. Shares in Ultragenyx were up more than 10% premarket this morning.

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XLH is a genetic disorder caused by mutations in the PHEX gene and is characterized by very low levels of phosphate in the blood, which affects the health of bones and can cause rickets and small stature. It affects about one in 20,000 people, and the severity of symptoms can vary widely, according to the XLH Network charity.

The trial enrolled 134 adult patients with the painful disorder, who were randomized to receive a 1mg/kg dose of burosumab every 4 weeks or a placebo over a 24-week study period. Data from that final timepoint show that normal range serum phosphorus levels were achieved in 94% of patients on burosumab, compared with just 8% in the placebo arm.

Measures of clinical symptoms of XLH such as stiffness and physical functioning also favored Ultragenyx's drug, with statistical improvements over control, while there was a trend toward an improvement in pain levels with burosumab, which is being developed in collaboration with Japanese drugmaker Kyowa Hakko Kirin.

Taken together, that equated to a meaningful improvement in patients' symptom scores that seemed to be sustained after the study period, according to the company, which said the results are in line with earlier phase 2 data. For good measure, there was also evidence for improved bone formation with burosumab suggesting that healing is starting to occur, and the company will glean further information on that as the patients continue to be followed up on through 48 weeks of treatment.

"Some investors may question FDA's perception of a small benefit on pain … but we believe larger improvements in 2/3 secondary endpoints should assuage concerns," said Leerink in a research note, noting that unlike current standard of care (with phosphate supplements and calcitriol) Ultragenyx's drug did not cause calcification in the kidneys or heart.

Ultragenyx's CEO Dr. Emil Kakkis told investors and analysts yesterday that the relatively short period of treatment cannot be expected to reverse years of disease progression in the study group. However, the study "provides clinical evidence that these patients have turned the corner from a lifetime of decline toward the beginnings of improvement," he said.

The data suggest burosumab has a "sustained effect on phosphate wasting," which is the underlying cause of the disease in XLH, continued Kakkis.

A second phase 3 trial that will look at bone-related endpoints such as osteomalacia or bone softening is fully enrolled with results expected around the turn of the year, and a pediatric trial is due to read out in 2018. Leerink says the company plans to file for U.S. approval of the drug in both adult and pediatric patients based on aggregated data.