Crysvita Treatment for Nearly 2 Years Continues to be Safe for XLH Patients, Trial Data Show

Crysvita Treatment for Nearly 2 Years Continues to be Safe for XLH Patients, Trial Data Show
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Treatment for nearly two years with Crysvita (burosumab) continued to maintain normal blood levels of phosphate and was found to be safe in adults with X-linked hypophosphatemia (XLH), according to final data from a Phase 3 trial.

The findings were published in an article, “Long-Term Safety in Adults with X-Linked Hypophosphatemia (XLH) Treated with Burosumab, a Fully Human Monoclonal Antibody Against FGF23: Final Results of a Phase 3 Trial,” in the Journal of the Endocrine Society. They were scheduled to be presented at the ENDO 2020 meeting, which was planned for late March but was cancelled due to the COVID-19 pandemic.

XLH is characterized by abnormally high levels of a bone-derived hormone called fibroblast growth factor 23 (FGF23) in the blood, preventing the kidneys from reabsorbing phosphate — an important bone component — into the bloodstream.

This leads to chronic hypophosphatemia (low blood levels of phosphate) and osteomalacia — the abnormal softening of bones, making them more prone to deformities and fractures, and less able to heal when damaged.

Crysvita, marketed by Ultragenyx Pharmaceutical and Kyowa Kirin, is currently the only disease-modifying therapy approved for the treatment of XLH. The therapy, given as an under-the-skin (subcutaneous) injection, is an antibody designed to block FGF23, thereby boosting phosphate reabsorption and increasing its levels in the blood.

A global Phase 3 trial (NCT02526160) evaluated the safety and effectiveness of Crysvita in 134 adults with XLH. Participants were randomly assigned to receive Crysvita at a dose of 1 mg/kg of body weight (68 patients) or a placebo (66 patients), every four weeks for 24 weeks (nearly six months). The study was sponsored by Ultragenyx with collaboration from Kyowa Kirin.

Results showed that Crysvita was safe, effectively normalized phosphate blood levels, improved bone health and healing, and eased stiffness compared with a placebo.

After this first part, participants joined an open-label study where all were treated with Crysvita for another 24 weeks. This was followed by an extension study, where the therapy was given for up to 96 weeks (nearly two years) to evaluate long-term safety and effectiveness.

Updated data from week 24 to 48 showed that the therapy resulted in normalization of phosphate levels in the blood, bone fracture healing, significant easing of stiffness and pain, as well as better physical function.

Available results from week 24 to 74 indicated no new safety concerns and no reports of treatment-related serious or life-threatening side effects.

Researchers had planned to present final long-term safety data of the extension study at the now-cancelled ENDO 2020 meeting.

A total of 119 participants (89%) completed the 96 weeks of treatment with 1 mg/kg of Crysvita. Dose reductions were required for 11 patients (8.2%) to effectively manage mild hyperphosphatemia (higher-than-normal blood levels of phosphate).

At week 94, participants’ mean levels of phosphorus in the blood (2.97 mg/dL) were within the normal range (2.8 to 4.5 mg/dL for adults).

“[Blood] phosphate was maintained with long-term [Crysvita] treatment, with no evidence of loss of effect in adults with XLH,” the researchers wrote.

The team also monitored two important complications of the current treatment options for XLH: nephrocalcinosis and hyperparathyroidism.

Nephrocalcinosis occurs when too much calcium is deposited in the kidneys, while hyperparathyroidism is characterized by higher-than-normal levels of parathyroid hormone (PTH), involved in calcium and phosphate balance.

At week 96, the nephrocalcinosis score remained unchanged for most patients, while it showed a small decrease in nine patients and a small increase in 10 patients; data from 14 participants were not available. There was also a progressive decline in PTH levels up to week 96, with levels still above the normal range (upper level of 65 picograms/mL).

In addition, no meaningful changes in deposition of calcium/phosphate complexes in soft tissues were detected.

Data also showed that the frequency, severity, and type of adverse events in this study were consistent with those reported in previous Crysvita trials. No signs of immune reactions against the therapy were found, as well as no treatment discontinuation due to adverse events.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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José holds a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.

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Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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