乌鸦传媒

BOSTON -- Burosumab (Crysvita), a fully human monoclonal antibody against fibroblast growth factor 23, improved rickets severity in kids with X-linked hypophosphatemia (XLH), researchers reported here.

According to two phase II trials, total Thacher Rickets Severity Score was significantly improved by week 40 of treatment, specifically by 61% in a group of children, ages 5-12 years, and 59% in children, ages 1-4 years, according Anthony Portale, MD, of University of California San Francisco, and colleagues.

A similar improvement was reported in Radiographic Global Impression of Change scores for both groups by week 40, he said in a presentation at the American Association of Clinical Endocrinologists (AACE) annual meeting.

"These findings suggest that early use of burosumab may result in positive clinical outcomes in children with XLH," Portale stated.

Burosumab was recently FDA approved for the treatment of adults and children (ages ≥1 year) with XLH, a rare, inherited form of rickets.

The randomized trial of older children included 52 participants (ages 5-12). Half received subcutaneous burosumab every 2 weeks, while the other half received treatment every 4 weeks for a total of 64 weeks. Doses were titrated up to a maximum dose of 2 mg/kg with target levels of fasting serum phosphorus levels from 3.5 to 5.0 mg/dL. At week 40, the average dose was around 1.0 mg/kg.

The trial of 13 young children (ages 1-4), all received a dose of subcutaneous burosumab of 0.8 m/kg every 2 weeks without a titration period. If serum phosphorus levels were persistently low, this dose was then increased up to 1.2 mg/kg. At week 40, the average dose was approximately 0.9 mg/kg.

Of the 39 patients from both studies who received treatment every 2 weeks, 36 were previously treated with oral phosphate and active vitamin D, which were discontinued prior to burosumab treatment.

In addition to rickets severity improvement, there were improvements in serum calcitriol levels. There was a 38% and 40% increase in serum phosphorus levels in the older and young age groups, respectively, with achievement of the reference range (3.2-6.1 mg/dL) prior to week 20 of treatment in older children and immediately after the first dose in the younger group. In contrast, there was a significant drop in alkaline phosphatase seen in both groups.

"Burosumab had a similar safety profile to previous pediatric trials, and adverse events were mild to moderate in severity," Portale noted. Only two participants experienced a severe adverse event (one in each group): a dental abscess in a younger patient and a fever with muscle pain that required hospitalization in an older one, he added.

Overall, none of the participants developed hyperphosphatemia, experienced any significant changes in serum or urine calcium or circulating parathyroid hormone levels, and no one dropped out of the study.

AACE attendee Camilo Jimenez, MD, of the MD Anderson Cancer Center in Houston, asked if burosumab is useful for patients with tumor-induced osteomalacia.

"The drug has been studied in patients with tumor-induced osteomalacia, and these patients do have high circulating FGF23, and the drug is very effective in treating these patients," Portale said. "There is a in these patients and it shows very similar findings -- it reverses the hypophosphatemia, and there's also improvement in the bone phenotype, and helps with other symptoms such as muscle weakness and bowing."

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