Category: Calcium/Bone Disorders

Monitor: 25

25 - SAFETY AND EFFICACY OF RECOMBINANT HUMAN PARATHYROID HORMONE 1-84 FOR THE TREATMENT OF ADULTS WITH CHRONIC HYPOPARATHYROIDISM: SIX-YEAR RESULTS OF THE RACE STUDY

Thursday, Apr 25
12:30 PM – 1:00 PM

Objective :

RACE is an open-label study that assessed the long-term safety and efficacy of recombinant human parathyroid hormone 1-84 (rhPTH[1-84]) for the treatment of hypoparathyroidism in adults (ClinicalTrials.gov NCT01297309). Here, we present 6-year safety and efficacy data.


Methods :

Patients initially received 25 or 50 µg/day of rhPTH(1-84) subcutaneously, once daily, with stepwise dose adjustments of 25 µg (up or down) to 100 µg/day max. rhPTH(1-84) could be titrated and oral calcium (Ca) and calcitriol doses adjusted at any time during the study to maintain albumin-corrected serum Ca levels in the target range of 8.0–9.0 mg/dL. A composite efficacy endpoint was the proportion of patients who achieved at least a 50% reduction from baseline (BL) in oral Ca dose (or Ca ≤500 mg/day) and at least a 50% reduction from BL in calcitriol dose (or calcitriol ≤0.25 µg/day), while normalizing or maintaining albumin-corrected serum Ca compared with BL value and not exceeding the upper limit of normal for the central laboratory. Descriptive summary statistics (mean[SD]) are shown.


Results :

The study cohort consisted of 49 patients enrolled at 12 US centers (mean age, 48.1[9.78] years; 81.6% female); data from 34 patients (69.4%) who completed 72 months (M72) of rhPTH(1-84) treatment as of July 17, 2018 are presented. Oral Ca and calcitriol doses were reduced by 40.4% and 72.2% at M72, respectively, and albumin-corrected serum Ca levels were maintained within target range (BL, 8.4[0.70] mg/dL; M72, 8.4[0.68] mg/dL). At M72, 22 of 34 patients (64.7%) achieved the composite efficacy endpoint. Urinary Ca excretion declined from above-normal at BL to within normal range (BL, 356.7[200.37] mg/24 h; M72, 213.2[128.82] mg/24 h). Mean serum creatinine levels remained stable (BL, 1.0[0.21] mg/dL; M72, 0.9[0.21] mg/dL), as did estimated glomerular filtration rate (eGFR; BL, 77.7[17.67] mL/min/1.73 m2; M72, 79.4[18.39] mL/min/1.73 m2). Serum phosphorus levels declined from above-normal at BL to within normal range (BL, 4.8[0.58] mg/dL; M72, 4.0[0.62] mg/dL); calcium-phosphorus product levels also declined (BL, 42.1[6.35] mg2/dL2; M72, 33.7[5.01] mg2/dL2). Treatment-emergent adverse events and treatment-emergent serious adverse events were reported in 98.0% and 26.5% of patients, respectively; no new safety concerns were identified.


Discussion :

All key parameters declined or remained stable over time with rhPTH(1-84) treatment with no new identified safety concerns.


Conclusion :

Continuous use of rhPTH(1-84) over 6 years resulted in a favorable safety profile, was effective, and improved key measurements of mineral homeostasis, notably normalization of urinary calcium.

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Henry Bone

Director
Michigan Bone & Mineral Clinic, PC, Detroit, MI, USA

Dr. Bone completed his AB in biology at Princeton University and received his MD from the University of Washington. He was an intern, resident and fellow at the University of Texas Southwestern Medical School and affiliated hospitals in Dallas, and was a postdoctoral scholar and assistant professor at U.C. San Diego and San Diego VAMC. He was director of clinical research for endocrinology at CIBA-Geigy, senior staff physician at Henry Ford Hospital, and is currently the director of the Michigan Bone & Mineral Clinic in Detroit. His focus has been on therapeutics for disorders of bone and mineral metabolism.

Bart L. Clarke

Consultant Metabolic Bone Disease Core Group and Professor of Medicine
Mayo Clinic Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Rochester, MN, USA

Dr. Clarke is Consultant in the Metabolic Bone Disease Core Group in the Division of Endocrinology, Diabetes, Metabolism, and Nutrition at the Mayo Clinic, and Professor of Medicine in the Mayo Clinic College of Medicine. He completed his medical training at the UCLA School of Medicine, and residency and fellowship training at the Mayo Graduate School of Medicine. His current clinical research interests include parathyroid disorders, including hypoparathyroidism and primary hyperparathyroidism, postmenopausal osteoporosis, glucocorticoid- and transplantation-induced osteoporosis, and tumor-induced osteomalacia. He is President of the American Society for Bone and Mineral Research, and a member of the American Association of Clinical Endocrinologists, Endocrine Society, and the American College of Physicians. He has served as a member of the Editorial Board for the Journal of Bone and Mineral Research, served on the FDA Reproductive Health Drug Advisory Board, and is a current chair of the Mayo Clinic Institutional Review Board.

On behalf of the RACE study

RACE Study Group
Sponsor; Shire Human Genetic Therapies, Inc., Cambridge, MA, USA

Members of the RACE study group: Henry Bone, Michigan Bone and Mineral Clinic, PC, Detroit, MI, USA; John P. Bilezikian, Columbia University College of Physicians and Surgeons, New York, NY, USA; Bart L. Clarke, Mayo Clinic, Rochester, MN, USA; Douglas Denham, Clinical Trials of Texas, Inc., San Antonio, TX, USA; Hak Myung Lee, Shire Human Genetic Therapies, Inc., Lexington, MA, USA; Michael A. Levine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA; Michael Mannstadt, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Munro Peacock, Indiana University School of Medicine, Indianapolis, IN, USA; Jeffrey Rothman, University Physicians Group – Research Division, Staten Island, NY, USA; Nicole Sherry, Shire Human Genetic Therapies, Inc., Cambridge, MA, USA; Dolores M. Shoback, SF Department of Veterans Affairs Medical Center, University of California, San Francisco, CA, USA; Tamara J. Vokes, University of Chicago Medicine, Chicago, IL, USA; Mark L. Warren, Endocrinology and Metabolism, Physicians East, PA, Greenville, NC, USA; Nelson B. Watts, Osteoporosis and Bone Health Services, Mercy Health, Cincinnati, OH, USA

Henry Bone

Director
Michigan Bone & Mineral Clinic, PC, Detroit, MI, USA

Dr. Bone completed his AB in biology at Princeton University and received his MD from the University of Washington. He was an intern, resident and fellow at the University of Texas Southwestern Medical School and affiliated hospitals in Dallas, and was a postdoctoral scholar and assistant professor at U.C. San Diego and San Diego VAMC. He was director of clinical research for endocrinology at CIBA-Geigy, senior staff physician at Henry Ford Hospital, and is currently the director of the Michigan Bone & Mineral Clinic in Detroit. His focus has been on therapeutics for disorders of bone and mineral metabolism.

John Bilezikian

Douglas Denham

Medical Director
Clinical Trials of Texas, Inc., San Antonio, TX, USA

Dr Denham is a Family Medicine physician with 12 years of research experience in the Metabolic Disease/Women’s Health/Dermatology and Psychiatry fields in San Antonio, Texas. He has been Medical Director of Clinical Trials of Texas for the last 8 years. He has experience in Phase I-IV studies as well as Medical Device experience.

Hak-Myung Lee

Michael A. Levine

Michael Mannstadt

Munro Peacock

Jeffrey Rothman

Dolores M. Shoback

Tamara J. Vokes

Mark L. Warren

Nelson B. Watts