番茄社区

MONTREAL -- The benefits of burosumab (Crysvita) among children with X-linked hypophosphatemia persisted to week 88, with sustained improvements in serum phosphorus and rickets severity, according to researchers here.

X-linked hypophosphatemia is a rare, debilitating bone disease mediated by circulating fibroblast growth factor-23 (FGF23). The skeletal deformities associated with the condition such as bowing of the legs can significantly impair motor function and quality of life in childhood and throughout the lifespan.

Burosumab is a fully human monoclonal antibody targeting FGF23 that showed efficacy and safety through week 40 in an . In that analysis, the Total Thatcher Rickets Severity Score (RSS) decreased from 1.9 at baseline to 0.8 at week 40 with every 2 week dosing (doses adjusted to achieve serum phosphorus levels at the low end of the normal range), and from 1.7 to 1.1 with every 4 week dosing (P<0.001 for both).

Burosumab was in April 2018 for children with X-linked hypophosphatemia ages ≥1 year.

"We are impressed with the persistent improvements with this new treatment for skeletal disease and patient well being," Thomas O. Carpenter, MD, of Yale University School of Medicine in New Haven, Connecticut, told 番茄社区 during his group's poster presentation at the American Society for Bone and Mineral Research annual meeting.

The study included 52 children with X-linked hypophosphatemia, ages 5 to 12 years, at baseline.

Initial dosages of burosumab were 0.1 mg/kg every 2 weeks or 0.2 mg/kg every 4 weeks, with titration to 0.2 or 0.3 mg/kg every 2 weeks or 0.4 or 0.6 mg/kg every 4 weeks up to 2 mg/kg, with the goal of achieving fasting serum phosphorus levels to within 3.5 to 5 mg/dL.

Participants underwent a washout from conventional therapy with oral phosphate and active vitamin D before study entry. "The children didn't like the older therapy, and would spit it out," Carpenter said.

Patients' mean age at baseline was 8.5 years, and slightly fewer than half were boys. Their mean height Z score was -1.72 in the every 2-week group and -2.05 in the every 4-week group. The majority were white. Mean rickets severity score was 1.8 at baseline, and almost all had previously received conventional therapy for a mean duration of almost 7 years.

At week 64, patients who initially were in the every 2-week dosing group were switched to the every 4-week group, and thereafter all patients received the treatment every 2 weeks.

Disease severity was assessed with the RSS and the Radiographic Global Impression of Change (RGI-C), which is a 7-point scale that measures changes at the wrist, knee, and leg.

At week 88, the mean RSS had declined from 1.9 in the every 2 week group to 0.9, and from 1.7 to 0.8 in the group originally receiving the treatment every 4 weeks. Also at week 88, the every 2 week group had global RGI-C scores of 1.7, which was unchanged from week 40, while patients who had switched from the every 4 week to the every 2-week group had scores of 1.8 compared with scores of 1.4 at week 40.

Significant increases in serum phosphorus also were sustained through week 88 and remained above the lower limit of normal for patients who switched from the every 4-week dosing group to the every 2-week group.

There also were sustained benefits in distance walked on the 6-minute walk test and in standing height Z-scores.

Reported adverse events included pain in an extremity in 40%, injection site reactions in 37%, arthralgias in 33%, myalgias in 14%, and vitamin D deficiency in 6%. There were no adverse events leading to discontinuation or death. There also were no clinically concerning changes in serum parathyroid hormone or serum or urinary calcium, and there were no cases of hyperphosphatemia.

"All the patients are staying on the treatment. We've been looking for safety signals, but the safety looks good," Carpenter said. "We don't know yet if the treatment affects dental abscesses. Those data are being analyzed."

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