New FDA Approved Treatment in Patients With Hypoparathyroidism and Hypocalcemia

By: Dimitrios Savva, PharmD Candidate c/o 2016

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Hypoparathyroidism is a rare disease that affects approximately 60,000 people in the United States.¹ People diagnosed with hypoparathyroidism are characterized as having insufficient levels of parathyroid hormone (PTH).² A person with this disease does not produce or secrete enough of PTH, leading to a decreased level of calcium in the blood, also known as hypocalcemia.

Hypoparathyroidism is caused by a loss of function of the parathyroid glands. The most common cause of hypoparathyroidism is neck surgery, with the removal or destruction of the parathyroid glands.³ Operations most often associated with hypoparathyroidism are cancer surgeries, total thyroidectomies, and parathyroidectomies⁴. Other causes of this rare disease include autoimmune disease and rare genetic disorders, such as DiGeorge syndrome, as well as familial isolated hypoparathyroidism.

PTH maintains calcium homeostatsis.⁴ It enhances active reabsorption of calcium in the kidney, primarily in the distal convoluted tubule, and absorption in the intestine by increasing renal production of the active vitamin D metabolite 1,25 (OH)₂D. ⁴ These mechanisms of PTH help promote the inflow of calcium into the extracellular fluid.

On January 23, 2015, the U.S Food and Drug Administration approved Natpara^® to control hypocalcemia in patients with hypoparathyroidism.¹ Natpara^® is a once-daily subcutaneous injectable recombinant PTH product that can be used as an adjunct to calcium and vitamin D supplementation.² Prior to the approval of Natpara^®, the standard of care for patients was supplementation of both calcium and active vitamin D. The goal of therapy is to maintain calcium levels; however, the use of these dietary supplementation provides inconsistent and inadequate regulation of biochemical indices as well as other complications (e.g., gastrointestinal issues).^2,3

Natpara^® is a recombinant PTH that assists in the increase of serum calcium by the same mechanisms as parathyroid hormone.⁵ The REPLACE trial is the pivotal trial for Natpara® therapy in hypoparathyroidism.³ The trial was a 24-week, randomized, double-blinded, placebo-controlled, multi-centered study. Patients in this trial were diagnosed with hypoparathyroidism, and were currently receiving calcium and active forms of vitamin D.⁵ The primary endpoints were: 50% or greater reduction from baseline of oral calcium dose, 50% or greater reduction from baseline of active vitamin D dose, and maintenance of a stable albumin corrected total serum calcium concentration greater than or equal to baseline concentration and less than or equal to the upper limit of normal, but ideally within the target range of 2.0–2.25 mmol/L.⁶ Results showed that 53% of patients in the Natpara® group achieved the primary endpoints established compared to one patient (2%) in the placebo group (percentage difference 51.1%; 95% CI 39.9–62.3; p<0.0001), and showed no difference in adverse or serious adverse events in either group.^3,6 The proportions of patients who had at least one adverse event were similar between groups (84  patients [93%] in the recombinant PTH group vs. 44 patients [100%]  in the placebo group), including hypocalcemia, muscle spasm, paraesthesias, headache, and nausea. The proportions of patients with serious adverse events were also similar between the recombinant PTH group (ten patients [11%]) and the placebo group (four patients [9%]) ⁶.

Natpara^® (parathyroid hormone) has proven itself to be a promising therapeutic option for patients with hypoparathyroidism.³ It gives people the chance to have control their disease and improve their ability to live with this rare disease.

 

SOURCES:

1. FDA approves Natpara to control low blood calcium levels in patients with hypoparathyroidism. U.S. Food and Drug Administration. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm431358.htm. Published 01/23/2015. Accessed 03/05/2015.
2. Nainggolan L. US FDA approves Natpara for hypoparathyroidism. Medscape. Available at http://www.medscape.com/viewarticle/838708. Published on 01/26/2015. Accessed on 03/05/2015.
3. Shoback D, Sellmeyer D, Bikle DD. Chapter 8. Metabolic Bone Disease. In: Gardner DG, Shoback D. eds. Greenspan’s Basic & Clinical Endocrinology, 9e. New York, NY: McGraw-Hill; 2011.
4. Cusano N, Rubin M, Bilezikian J. PTH (1-84) replacement therapy for the treatment of hypoparathyroidism. Expert Rev Endocrinol Metab. 2015;10(1): 5-15.
5. Natpara (parathyroid hormone) [package insert]. Bedminster, NJ; NPS Pharmaceuticals, Inc.; 01/2015.
6. 6. Mannstadt M, Clarke B, Vokes T, et al. Efficacy and safety of recombinant human parathyroid hormone (1–84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study. Lancets Diabetes Endocrinol. 2013;1(4):275-283.

[pubmed_related keyword1=”hypoparathyroidism” keyword2=”PTH” keyword3=”parathyroid”]