ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2018) 56 GP180 | DOI: 10.1530/endoabs.56.GP180

Five-year efficacy and safety of recombinant human parathyroid hormone 1-84 (rhPTH[1-84]) for the treatment of adults with chronic hypoparathyroidism: analysis from the open-label race study

Bart L Clarke1, Dolores M Shoback2, John P Bilezikian3, Henry Bone4, Douglas Denham5, Michael A Levine6, Michael Mannstadt7, Munro Peacock8, Jeffrey Rothman9, Tamara J Vokes10, Mark L Warren11, Nelson B Watts12, Hak-Myung Lee13 & Nicole Sherry13

1Mayo Clinic Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Rochester, Minnesota, USA; 2Endocrine Research Unit, SF Department of Veterans Affairs Medical Center, University of California, San Francisco, California, USA; 3Division of Endocrinology, College of Physicians and Surgeons, Columbia University, New York, USA; 4Michigan Bone and Mineral Clinic, PC, Detroit, Michigan, USA; 5Clinical Trials of Texas, Inc., San Antonio, Texas, USA; 6Division of Endocrinology and Diabetes and Center for Bone Health, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; 7Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; 8Department of Medicine, Division of Endocrinology, Indiana University School of Medicine, Indianapolis, Indiana, USA; 9University Physicians Group – Research Division, Staten Island, New York, USA; 10Section of Endocrinology, University of Chicago Medicine, Chicago, Illinois, USA; 11Endocrinology and Metabolism, Physicians East, PA, Greenville, South Carolina, USA; 12Osteoporosis and Bone Health Services, Mercy Health, Cincinnati, Ohio , USA; 13Shire Human Genetic Therapies, Inc., Lexington, Massachusetts, USA.

Hypoparathyroidism is a disorder of mineral homoeostasis due to parathyroid hormone (PTH) deficiency. Conventional treatment with oral Ca and calcitriol may maintain serum Ca levels but does not replace other physiologic PTH effects. RACE is an ongoing open-label study of recombinant human PTH1-84 (rhPTH1-84) for hypoparathyroidism treatment in adults ( NCT01297309). Patients initially received rhPTH1-84 25 or 50 μg/day subcutaneously, with 25-μg increases to 100 μg/day maximum. rhPTH(1-84) could be titrated and oral Ca/calcitriol doses adjusted at any time during the study to maintain serum Ca levels within the optimised target (2.0–2.2 mmol/l). Primary objective was to demonstrate the long-term safety and tolerability of rhPTH1-84. Composite efficacy endpoint was the proportion of patients who achieved a ≥50% reduction from baseline (BL) in oral Ca dose (or Ca ≤500 mg/day) and a ≥50% reduction from BL in calcitriol dose (or calcitriol ≤0.25 μg/day) while maintaining albumin-adjusted serum Ca between 1.87 mmol/l and the ULN for the central laboratory. Five-year, open-label efficacy and safety data presented with descriptive summary statistics (mean(S.D.)). Study cohort included 49 adult patients enrolled at 12 US centres (age 48.1[9.78] years; 81.6% female); 40 patients (81.6%) completed 60 months (M60) of rhPTH(1-84) as of 8 May 2017. Oral Ca and calcitriol doses were reduced by 53.4% and 75.7%, respectively; albumin-adjusted serum Ca levels were maintained within the target range (M60, 2.1[0.20] mmol/l; BL, 2.1[0.17] mmol/l). At M60, the efficacy composite endpoint was achieved by 28/40 patients. Urinary Ca excretion showed a numerical reduction (M60, 6.2[3.30] mmol/24 h; BL, 8.9[5.01] mmol/24 h, n=48), as did serum P levels (M60, 1.3[0.21] mmol/l; BL, 1.6[0.19] mmol/l,) and Ca-P product levels (M60, 2.8[0.45] mmol2/l2; BL, 3.4[0.51] mmol2/l2). Serum creatinine levels remained stable (M60, 81.7[19.85] μmol/l; BL, 84.7±18.16 μmol/l), as did estimated glomerular filtration rate (M60, 108.1[42.32] ml/min; BL, 108.2[36.36] ml/min, n=41). Treatment-emergent adverse events (TEAEs) were reported in 48/49 patients. Common TEAEs (>25% of patients) reported included symptoms of the underlying disease (ie, hypocalcaemia [36.7%], muscle spasms [32.7%], paraesthesia [30.6%]), sinusitis (30.6%), and nausea (30.6%). Serious TEAEs occurred in 13 patients. Continuous use of rhPTH1-84 over 5 years has an acceptable safety profile, was well tolerated, efficacious, and improved key measurements of mineral homoeostasis.