Self-Administration of Burosumab in Children and Adults with X-Linked Hypophosphataemia in Two Open-Label, Single-Arm Clinical Studies

Abstract

Introduction X-linked hypophosphataemia (XLH) is a rare, genetic renal phosphate-wasting disease, resulting from excess fibroblast growth factor 23 (FGF23) activity, which has a progressive and profound impact on patients throughout life. The monoclonal anti-FGF23 antibody, burosumab, is a subcutaneous injection indicated for the treatment of XLH in children and adults. Originally, burosumab was approved to be administered by a healthcare professional (HCP), but the option of self-administration would enable patient independence and easier access to treatment. Two open-label, single-arm clinical trials, conducted in Japan and Korea, have assessed the safety and efficacy of self-administration of burosumab in both children and adults with XLH. Methods In KRN23-003 ( n = 15 children aged 1–12 years) and KRN23-004 ( n = 5 children aged 3–13 years, n = 4 adults aged 21–65 years), children initially received 0.8 mg/kg of burosumab every 2 weeks and adults initially received 1.0 mg/kg of burosumab every 4 weeks. Self-administration was permitted from Week 4, and patients or carers were provided with training to inject correctly. Results In both trials, burosumab had an acceptable safety profile with mainly mild-to-moderate adverse events. Following self-administration, no patients reported serious treatment-emergent adverse events ≥ grade 3, injection-site reactions or hypersensitivity reactions related to burosumab. Serum phosphate and active vitamin D levels increased from baseline in children and adults. Conclusions These results indicated that the efficacy and safety of burosumab when administered either by a carer or patient are similar to that when administered by an HCP and show that self-administration is a viable option for patients with XLH. Trial Registration Numbers NCT03233126 and NCT04308096. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02412-x.

Real‐world data of Brazilian adults with X‐linked hypophosphatemia (XLH) treated with burosumab and comparison with other worldwide cohorts

“…The burden of XLH in adult patients is substantial, and there is no consensus about treating these patients with conventional therapy (Lecoq et al, 2020) When the medication was discontinued, symptoms recurred, but improved after restarting the therapy (Kamenicky et al, 2023). Burosumab is subcutaneously administered every 4 weeks, improving the adherence to therapy by adult patients, and self-administration showed to be safe both in children and adults (Kubota et al, 2023). Clinical trials are the most important tool available to verify the effects of a treatment.…”

“…When the medication was discontinued, symptoms recurred, but improved after restarting the therapy (Kamenicky et al., 2023). Burosumab is subcutaneously administered every 4 weeks, improving the adherence to therapy by adult patients, and self‐administration showed to be safe both in children and adults (Kubota et al., 2023).…”

Burosumab - new potent treatment for X-linked hypophosphatemia and tumor-induced osteomalacia

“…Originally, burosumab was approved to be administered by a healthcare professional, but the possibility of selfadministration might be beneficial for patients as it can provide easier access to treatment. As mentioned, the study conducted in Japan and Korea by Kubota et al which has assessed the safety and efficacy of self-administration of burosumab, proved that it is a viable option also for children with XLH [16]. The effect of burosumab on dental health in ten children with XLH has been assessed by Brener et al This trial revealed that dental morphology of XLH patients, distinguished by increased pulp-coronal ratios compared to controls (p=0.002), remained larger after the first year of treatment (p<0.001) and did not attain the decrease expected with age after three years of treatment.…”

“…As burosumab is gaining more attention worldwide, recently, the efficacy and safety of self-administration was evaluated in two open-label, single-arm clinical trials and the results revealed that burosumab can be successfully self-managed by patients without significant impact on effectiveness. Studies also did not highlight serious AE [16]. Although clinical trials show mostly positive impact on treating XLH with burosumab, further research is needed to evaluate its specific role in different phenotypes of XLH.…”