Rare Disease Report

Therapy for Rare Form of Rickets Approved by FDA

APRIL 17, 2018
Mathew Shanley
Burosumab (Crysvita) was approved this morning by the U.S. Food and Drug Administration (FDA) to treat adults and children ages 1 year and older with x-linked hypophosphatemia (XLH), a rare genetic variation of rickets.

With today’s regulatory action, the therapy becomes the first drug approved specifically for this indication. In October 2017, it was announced that the FDA had accepted the Biologics License Application (BLA) for burosumab, and the drug was granted a Priority Review status with today as its designated Prescription Drug User Fee Act (PDUFA) action date.

“XLH differs from other forms of rickets in that vitamin D therapy is not effective,” stated Julie Beitz, M.D., director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research in a press release. “This is the first FDA-approved medication for the treatment of XLH and a real breakthrough for those living with this serious disease.”

The impetus for the approval is backed by data that was first presented at The American Society for Bone and Mineral Research (ASBMR) 2017 Annual Meeting in Denver in September 2017, exhibiting the drug to be effective and safe.
In the presentation, Karl Insogna, M.D., of the Yale School of Medicine concluded that 94% of patients taking burosumab had serum phosphorous levels above 2.5 mg.dL, compared to only 7.6% in the placebo group after 24 weeks of treatment. Further, 44% of the patients in the burosumab had healed fractures compared to only 18% in the placebo group.

The safety and efficacy of burosumab were evaluated in 4 total clinical trials. In the placebo-controlled trial, 94% of adults receiving the drug once a month achieved normal phosphorus levels compared to 8% of those receiving placebo.

In children, 94% to 100% of patients administered burosumab every other week achieved normal phosphorus levels. In both children and adults, X-ray findings associated with XLH improved with burosumab therapy. Comparison of the results to a natural history cohort also supported the effectiveness of burosumab.

Burosumab is a monoclonal IgG1 antibody directed against the phosphaturic hormone fibroblast growth factor 23 (FGF23), a hormone that reduces serum levels of phosphorus and active vitamin D. By inhibiting this hormone, burosumab can increase phosphate and vitamin D.

The condition is characterized by inadequate mineralization of bone that leads to a spectrum of abnormalities, including rickets, progressive bowing of the leg, osteomalacia, bone pain, waddling gait, short stature, gross motor impairment, muscle weakness, frequent/poorly healing pseudofractures, spinal stenosis, enthesopathy, and osteoarthritis.

Before today, there were no approved therapies that act directly on this phosphate wasting condition, and most pediatric patients are managed using oral phosphate replacement and vitamin D (calcitriol) therapy.

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