2020
Burosumab for the Treatment of Tumor‐Induced Osteomalacia
de Beur S, Miller PD, Weber TJ, Peacock M, Insogna K, Kumar R, Rauch F, Luca D, Cimms T, Roberts MS, San Martin J, Carpenter TO. Burosumab for the Treatment of Tumor‐Induced Osteomalacia. Journal Of Bone And Mineral Research 2020, 36: 627-635. PMID: 33338281, PMCID: PMC8247961, DOI: 10.1002/jbmr.4233.Peer-Reviewed Original ResearchConceptsTumor-induced osteomalaciaCutaneous skeletal hypophosphatemia syndromeSerious adverse eventsAdverse eventsWeek 144Week 48Serum phosphorusTreatment-related adverse eventsFibroblast growth factor 23Surface/bone surfaceAcceptable safety profileOsteoid surface/bone surfacePhase 2 studyGrowth factor 23Phosphaturic mesenchymal tumorTransiliac bone biopsiesHuman monoclonal antibodyMineralization lag timePhosphate metabolismQuality of lifeDose titrationFactor 23Safety profileMesenchymal tumorsSkeletal healthLong-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
Kamenický P, Portale A, Carpenter T, Briot K, Imel E, Weber T, Pitukcheewanont P, Cheong H, de Beur S, Imanishi Y, Ito N, Lachmann R, Tanaka H, Perwad F, Zhang L, Skrinar A, Rees L, Insogna K, Investigators O. 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. Bone Reports 2020, 13: 100654. DOI: 10.1016/j.bonr.2020.100654.Peer-Reviewed Original ResearchPhase 3 trialLong-term safetyHuman monoclonal antibodyMonoclonal antibodiesBurosumabHypophosphatemiaFGF23OR29-01 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
Perwad F, Portale A, Carpenter T, Briot K, Imel E, Kamenicky P, Weber T, Pitukcheewanont P, Cheong H, De Beur S, Imanishi Y, Ito N, Lachmann R, Tanaka H, Zhang L, Skrinar A, Rees L, Insogna K. OR29-01 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. Journal Of The Endocrine Society 2020, 4: or29-01. PMCID: PMC7209551, DOI: 10.1210/jendso/bvaa046.147.Peer-Reviewed Original ResearchYears of ageSerum phosphorusWeek 96Dose reductionLong-term safety resultsTreatment-emergent adverse eventsMonoclonal antibodiesBaseline serum phosphorusHuman IgG1 monoclonal antibodyMean iPTH levelPhase 3 trialLong-term safetyHuman monoclonal antibodyConditional marketing authorizationMonths of ageIgG1 monoclonal antibodyIPTH levelsPlacebo groupAdverse eventsTreatment withdrawalWeek 24Radiographic evidenceMulticenter studyBurosumab treatmentMild hyperphosphatemiaSUN-333 Burosumab Improves Bone Density in Patients with X-Linked Hypophosphatemia
Murari K, Insogna K. SUN-333 Burosumab Improves Bone Density in Patients with X-Linked Hypophosphatemia. Journal Of The Endocrine Society 2020, 4: sun-333. PMCID: PMC7207437, DOI: 10.1210/jendso/bvaa046.1470.Peer-Reviewed Original ResearchTrabecular bone scoreBone mineral densityL-spine bone mineral densityTotal hip bone mineral densityHip bone mineral densityBone scorePhase III clinical trialsRegional bone mineral densityRenal phosphate leakCourse of treatmentHuman monoclonal antibodyConsiderable clinical relevanceSignificant increaseFGF-23Frequent siteClinical trialsMineral densityMineral metabolismBone densityDrug treatmentPhosphate leakBurosumabBMD measurementsClinical relevanceStudy subjectsOR29-06 Burosumab Improves Biochemical, Skeletal, and Clinical Features of Tumor-Induced Osteomalacia Syndrome
Carpenter T, Miller P, Weber T, Peacock M, Insogna K, Kumar R, Luca D, Cimms T, Roberts M, de Beur S. OR29-06 Burosumab Improves Biochemical, Skeletal, and Clinical Features of Tumor-Induced Osteomalacia Syndrome. Journal Of The Endocrine Society 2020, 4: or29-06. PMCID: PMC7208350, DOI: 10.1210/jendso/bvaa046.403.Peer-Reviewed Original ResearchTumor-induced osteomalaciaCutaneous skeletal hypophosphatemia syndromeSerious adverse eventsAdverse eventsSerum phosphorusBone biopsyPhysical functioningMean physical component summary scoreOpen-label phase 2 studyPhysical component summary scoreOsteoid volume/bone volumeSurface/bone surfaceProximal muscle functionBrief Pain InventoryOsteoid surface/bone surfacePhase 2 studyComponent summary scoresTmP/GFRCrest bone biopsiesRenal phosphate wastingHuman monoclonal antibodyMineralization lag timeQuality of lifeExcess FGF23Bone scan
2019
Burosumab Improved Histomorphometric Measures of Osteomalacia in Adults with X‐Linked Hypophosphatemia: A Phase 3, Single‐Arm, International Trial
Insogna KL, Rauch F, Kamenický P, Ito N, Kubota T, Nakamura A, Zhang L, Mealiffe M, San Martin J, Portale AA. 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 2019, 34: 2183-2191. PMID: 31369697, PMCID: PMC6916280, DOI: 10.1002/jbmr.3843.Peer-Reviewed Original ResearchConceptsAdverse eventsWeek 48Fracture healingMore treatment-emergent adverse eventsTreatment-emergent adverse eventsProcedure-related adverse eventsOsteoid volume/bone volumeMost adverse eventsSerious adverse eventsTransiliac bone biopsiesSerum phosphorus concentrationPoor bone qualityRenal phosphate reabsorptionHuman monoclonal antibodyBone painPersistent osteomalaciaSubcutaneous burosumabPrimary endpointSkeletal complicationsAtraumatic fracturesChronic hypophosphatemiaSerum phosphorusDihydroxyvitamin DBone turnoverBone biopsyContinued 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
Portale AA, Carpenter TO, Brandi ML, Briot K, Cheong HI, Cohen-Solal M, Crowley R, Jan De Beur S, Eastell R, Imanishi Y, Imel EA, Ing S, Ito N, Javaid M, Kamenicky P, Keen R, Kubota T, Lachmann R, Perwad F, Pitukcheewanont P, Ralston SH, Takeuchi Y, Tanaka H, Weber TJ, Yoo HW, Zhang L, Theodore-Oklota C, Mealiffe M, San Martin J, Insogna K. 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 2019, 105: 271-284. PMID: 31165191, DOI: 10.1007/s00223-019-00568-3.Peer-Reviewed Original ResearchConceptsWeek 48Adverse eventsWeek 24Sustained improvementTreatment-related serious adverse eventsOpen-label treatment periodSafety of burosumabDouble-blind placeboFatal adverse eventsSerious adverse eventsSerum phosphorus levelsPatient-reported outcomesSerum phosphorus concentrationRenal phosphate wastingHuman monoclonal antibodyContinued beneficial effectsHealing of fracturesRare genetic disorderMusculoskeletal morbidityPhysical functionContinuation periodMusculoskeletal impairmentsPhosphate wastingTreatment periodBurosumabOR13-1 Burosumab Improves the Biochemical, Skeletal, and Clinical Symptoms of Tumor-Induced Osteomalacia Syndrome
De Beur S, Miller P, Weber T, Peacock M, Insogna K, Kumar R, Luca D, Theodore-Oklota C, Lampl K, San Martin J, Carpenter T. OR13-1 Burosumab Improves the Biochemical, Skeletal, and Clinical Symptoms of Tumor-Induced Osteomalacia Syndrome. Journal Of The Endocrine Society 2019, 3: or13-1. PMCID: PMC6554835, DOI: 10.1210/js.2019-or13-1.Peer-Reviewed Original ResearchMineralization lag timeTumor-induced osteomalaciaSerum phosphorusAdverse eventsOsteoid thicknessTumor progressionBone biopsyDose intervalMean physical component summary scoreOpen-label phase 2 studyPP groupPhysical component summary scoreOsteoid volume/bone volumeSurface/bone surfaceMean serum phosphorusPhase 2 studySerious adverse eventsOsteoid surface/bone surfaceComponent summary scoresCrest bone biopsiesMean percentage changeEpidermal nevus syndromeRenal phosphate wastingHuman monoclonal antibodyOS/BS
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
Insogna KL, Briot K, Imel EA, Kamenický P, Ruppe MD, Portale AA, Weber T, Pitukcheewanont P, Cheong HI, de Beur S, Imanishi Y, Ito N, Lachmann RH, Tanaka H, Perwad F, Zhang L, Chen C, Theodore‐Oklota C, Mealiffe M, San Martin J, Carpenter TO, Investigators O. 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 2018, 33: 1383-1393. PMID: 29947083, DOI: 10.1002/jbmr.3475.Peer-Reviewed Original ResearchConceptsTreatment-related serious adverse eventsMean serum phosphate concentrationWOMAC physical function subscaleFibroblast growth factor 23Intact parathyroid hormoneSerious adverse eventsPhase 3 trialPhysical function subscaleChronic musculoskeletal painGrowth factor 23Serum phosphate concentrationRenal phosphate wastingHuman monoclonal antibodyLower limb deformitiesImportant medical needStiffness subscalePlacebo groupUrine calciumWorst painAdverse eventsWeek 24Dental abscessMusculoskeletal painFactor 23Function subscale
2013
Denosumab For The Treatment Of Hypercalcemia Of Malignancy Refractory To IV Bisphosphonates In Patients With Hematologic Malignancies
Gucalp R, Insogna K, Hu M, Glezerman I, Leboulleux S, Misiorowski W, Yu B, Zorsky P, Tosi D, Bessudo A, Jaccard A, Tonini G, Ying W, Braun A, Jain R. Denosumab For The Treatment Of Hypercalcemia Of Malignancy Refractory To IV Bisphosphonates In Patients With Hematologic Malignancies. Blood 2013, 122: 2536. DOI: 10.1182/blood.v122.21.2536.2536.Peer-Reviewed Original ResearchHypercalcemia of malignancyProportion of patientsSerious adverse eventsTreatment of hypercalcemiaHematologic malignanciesTreatment responseComplete responseDay 10Bisphosphonate treatmentStudy visitRANK ligandAmgen Inc.Unexpected safety findingsKey secondary endpointOpen-label studyHematologic malignancy patientsOverall study populationUse of denosumabKey baseline characteristicsStudy of patientsOff-label useHuman monoclonal antibodyBisphosphonate therapyDenosumab initiationSubcutaneous denosumab