Recombinant Human Parathyroid Hormone, (rhPTH[1-84], Parathyroid Hormone rDNA) Improves Hypercalciuria in Patients with Hypoparathyroidism: 3-Year Analysis from Race Study

Presentation Number: OR06-2
Date of Presentation: April 4th, 2017

Tamara J. Vokes1, John P. Bilezikian2, Henry G. Bone III3, Bart Lyman Clarke4, Douglas S. Denham5, Hak-Myung Lee6, Michael A. Levine7, Michael Mannstadt8, Munro Peacock9, Jeffrey G. Rothman10, Dolores M. Shoback11, Mark Lowe Warren12, Nelson B. Watts*13 and Alan Krasner6
1University of Chicago Medicine, Chicago, IL, 2College of Physicians and Surgeons, Columbia University, New York, NY, 3Michigan Bone and Mineral Clinic, PC, Detroit, MI, 4Mayo Clinic E18-A, Rochester, MN, 5Clinical Trials of Texas, Inc., San Antonio, TX, 6Shire Human Genetic Therapies, Inc., Lexington, MA, 7The Children's Hospital of Philadelphia, Philadelphia, PA, 8Massachusetts General Hospital and Harvard Medical School, Boston, MA, 9Indiana University School of Medicine, Indianapolis, IN, 10Staten Island University Hospital, Staten Island, NY, 11SF Department of Veterans Affairs Medical Center, University of California, San Francisco, CA, 12Physicians East, PA, Greenville, NC, 13Mercy Health Osteoporosis and Bone Health Services, Cincinnati, OH

Abstract

Hypoparathyroidism is an uncommon endocrine disorder characterized by hypocalcemia, and impaired renal phosphate excretion and calcium conservation, due to parathyroid hormone (PTH) insufficiency. Conventional management with oral calcium supplements and calcitriol can improve serum calcium levels, but lacks the physiologic effects of PTH on renal reabsorption of calcium. Conventional management frequently results in hypercalciuria which is often treated with thiazide diuretics to promote renal calcium reabsorption and to reduce the risk of renal calcification. RACE is an ongoing open-label study in the United States to evaluate the long-term safety of recombinant human parathyroid hormone 1-84 (rhPTH[1-84], parathyroid hormone rDNA) in adult patients with hypoparathyroidism (ClinicalTrials.gov identifier NCT01297309). In this interim dataset analysis, we report the 3-year treatment effect with 25–100 μg/day rhPTH(1-84) on 24-hour urinary calcium levels, with or without thiazide diuretics. All data are presented as mean (SD). The study cohort was comprised of 49 patients enrolled at 12 US centers; 38 (78%) completed 36 months of rhPTH(1-84) treatment. Patients at baseline were 82% women, 48 (9.8) years of age, with a duration of hypoparathyroidism of 16 (12.5) years, and taking prescribed calcium supplements and calcitriol. In response to rhPTH(1-84), albumin-corrected serum calcium remained within the target range over the 3 years; 8.4 (0.7) mg/dL at baseline (i.e., start of rhPTH[1-84], n=49) and 8.2 (0.7) mg/dL at Month 36 (n=36). Treatment with rhPTH(1-84) also led to a significant reduction in urinary calcium, from 356 (200) mg/24 hour at baseline to 260 (112) mg/24 hour at Month 36 (n=35; P=0.05). The urinary calcium excretion at Month 36 was similar for men compared with women: 308 (96) mg/24 hour, n=8 vs 244 (116) mg/24 hour, n=27 (P=0.18). The reduction in 24-hour urinary calcium in response to rhPTH(1-84) was similar in patients who were taking or not taking thiazide diuretics. Overall, 71% of rhPTH(1-84)-treated patients with baseline hypercalciuria had normal 24-hour urinary calcium excretion at Month 36 (n=12/17). Treatment with rhPTH(1-84) also improved the calcium-phosphate product from 42.1 (6.3) mg2/dL2 (n=49) at baseline to 35.9 (6.2) mg2/dL2 (n=36) at Month 36 (P<0.01). The eGFR was 108.2 (36.4) mL/min (n=41) at baseline and 115.7 (47.3) mL/min (n=36) at Month 36 (P=0.77). This analysis provides evidence on the long-term effect of rhPTH(1-84) on urinary calcium excretion in patients with hypoparathyroidism. Over 3 years, rhPTH(1-84) maintained target levels of serum calcium and reduced urinary calcium to normal levels. More information is needed to understand the timing of the beneficial effect on urinary calcium excretion.

 

Disclosure: TJV: Advisory Group Member, NPS-Shire, Investigator, NPS-Shire. JPB: Investigator, NPS-Shire, Advisory Group Member, NPS-Shire. HGB III: Investigator, NPS-Shire. BLC: Investigator, NPS-Shire, Advisory Group Member, NPS-Shire. DSD: Investigator, NPS-Shire. HML: Employee, Shire. MAL: Advisory Group Member, NPS-Shire. MM: Advisory Group Member, NPS-Shire. MP: Investigator, NPS-Shire. JGR: Investigator, NPS-Shire, Advisory Group Member, NPS-Shire. DMS: Investigator, NPS-Shire, Advisory Group Member, NPS-Shire. MLW: Investigator, NPS-Shire. NBW: Investigator, NPS-Shire. AK: Employee, Shire.