E-Poster Presentation ESA-SRB-ANZBMS 2021

Burosumab in Adult X-Linked Hypophosphatemia (#776)

Bella Halim 1 , Thuy Vu 1 , Suresh Varadarajan 1
  1. Endocrinology, Northern Health, Melbourne, VIC, Australia

X-linked Hypophosphatemia (XLH) is a rare X-linked dominant disorder with complete penetrance, caused by loss-of-function mutations in PHEX gene, which encodes an enzyme that degrades osteopontin and suppresses fibroblast growth factor 23 (FGF23)1,2. Treatment option for adults was limited to phosphate-calcitriol therapy that is poorly tolerated and does not address the underlying pathophysiology of XLH.

In 2018, a randomized controlled trial (RCT) assigned adults between 18 and 65 years of age with confirmed PHEX mutation to receive either burosumab, a monoclonal IgG1 antibody that targets FGF23 expression, at 1mg/kg every 4 weeks (burosumab-burosumab group) or placebo for 24 weeks3. This was followed by open-label burosumab to all subjects for 24 weeks (placebo-burosumab group). Primary analysis at week 24 shows 94.1% participants in the burosumab-burosumab group attained normal phosphate level and greater fracture healing compared to control3,4. Unfortunately, this medication is not widely available yet.

 

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We present a case of a 55 years old female with XLH that suffers from hypophosphatemia, hyperparathyroidism and non-healing left femoral fracture. This was further complicated by her inability to tolerate phosphate-calcitriol treatment. Her three children and granddaughter also have XLH.

Our burosumab application for her and her children has been approved. We believe that this is the first time burosumab has been approved for use in adult XLH patients in Australia. We aim that we will be able to report on her improvements at the time of ESA-SRB-ANZBMS 2021.

  1. Haffner, D., Emma, F., Eastwood, D.M., Duplan, M.B., Bacchetta, J., Schnabel, D., Wicart, P., Bockenhauer, D., Santos, F., Levtchenko, E. and Harvengt, P., 2019. Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia. Nature Reviews Nephrology, 15(7), pp.435-455.
  2. Insogna, K.L., Rauch, F., Kamenický, P., Ito, N., Kubota, T., Nakamura, A., Zhang, L., Mealiffe, M., San Martin, J. and Portale, A.A., 2019. Burosumab improved histomorphometric measures of osteomalacia in adults with X‐linked hypophosphatemia: a phase 3, single‐arm, international trial. Journal of Bone and Mineral Research, 34(12), pp.2183-2191.
  3. Insogna, K.L., Briot, K., Imel, E.A., Kamenický, P., Ruppe, M.D., Portale, A.A., Weber, T., Pitukcheewanont, P., Cheong, H.I., Jan de Beur, S. and Imanishi, Y., 2018. A randomized, double‐blind, placebo‐controlled, phase 3 trial evaluating the efficacy of burosumab, an anti‐FGF23 antibody, in adults with X‐linked hypophosphatemia: week 24 primary analysis. Journal of Bone and Mineral Research, 33(8), pp.1383-1393.
  4. Portale, A.A., Carpenter, T.O., Brandi, M.L., Briot, K., Cheong, H.I., Cohen-Solal, M., Crowley, R., De Beur, S.J., Eastell, R., Imanishi, Y. and Imel, E.A., 2019. Continued beneficial effects of burosumab in adults with X-linked hypophosphatemia: results from a 24-week treatment continuation period after a 24-week double-blind placebo-controlled period. Calcified tissue international, 105(3), pp.271-284.