Insogna and cols., 2018 (2727 Insogna KL, Briot K, Imel EA, Kamenický P, Ruppe MD, Portale AA, et al.; AXLES 1 Investigators. 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. J Bone Miner Res. 2018;33(8):1383-93.) |
Phase 3, randomized, double-blind, placebo-controlled, multicenter in adult patients (18 to 65 years old) with XLH for 24 weeks. |
Proportion of subjects achieving a mean serum phosphate concentration above the LLN of 2.5 mg/dL (0.81 mmol/L). |
134 patients (burosumab group = 68; placebo group = 66). |
94.1% of participants in the burosumab group versus 7.6% in the placebo group achieved a mean serum phosphate concentration above the LLN (p < 0.001). |
Portale and cols., 2019 (2828 Portale AA, Carpenter TO, Brandi ML, Briot K, Cheong HI, Cohen-Solal M, et al. 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. Calcif Tissue Int. 2019;105(3):271-84.) (Extension of Isogna and cols., 2018) |
Phase 3, randomized, double-blind, placebo-controlled, multicenter in adult patients (18 to 65 years old) with XLH for 48 weeks. |
Compared the efficacy of burosumab and placebo through week 24. |
134 patients, by week 24, 68 patients were in the burosumab group and 66 in the placebo group. After week 24 until week 48, all subjects received burosumab. |
In weeks 24 to 48, phosphorus concentrations remained normal in 83.8% of participants who received burosumab and were normalized in 89.4% of participants who received burosumab after the placebo. |
Briot and cols., 2021 (2929 Briot K, Portale AA, Brandi ML, Carpenter TO, Cheong HI, Cohen-Solal M, et al. Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension. RMD Open. 2021;7(3):e001714.) (Extension of Isogna and cols., 2018) |
Phase 3, randomized, double-blind, placebo-controlled, multicenter in adult patients (18 to 65 years old) with XLH for 96 weeks. |
Effect of burosumab on physical function, stiffness, pain, and fatigue (at weeks 24, 48, and 96) and ambulatory function (at weeks 24, 48, and 72) compared with baseline. |
134 patients: by week 24, 68 patients were in the burosumab group and 66 were in the placebo group. After week 24 until week 96, all subjects received burosumab. |
At week 96, all patients achieved a statistically significant improvement in pain inventory (BPI-SF), BFI, and stiffness (WOMAC) scores. Improvements in the 6-minute walking distance test and the predicted percentage were statistically significant from weeks 24 to 96. |
Insogna and cols., 2019 (3030 Insogna KL, Rauch F, Kamenický P, Ito N, Kubota T, Nakamura A, et al. Burosumab Improved Histomorphometric Measures of Osteomalacia in Adults with X-Linked Hypophosphatemia: A Phase 3, Single-Arm, International Trial. J Bone Miner Res. 2019;34(12):2183-91.) (Extension of Isogna and cols., 2018) |
Phase 3, randomized, double-blind, placebo-controlled, multicenter in adult patients (18 to 65 years old) with XLH for 48 weeks. |
Improvement in osteoid volume/bone volume assessed by trans iliac bone biopsies obtained at baseline and week 48. |
13 completed 48 weeks, and 11 completed paired biopsies. |
All osteomalacia-related histomorphometric measures improved significantly at week 48 (mean percent change: osteoid volume/bone volume, –54%; osteoid thickness, –32%; osteoid surface/bone surface, 26%; [median] mineralization lag time, 83%). |