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Natural form of parathyroid hormone decreased need for vitamin D, calcium in adults with hypoparathyroidism

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HOUSTON — Adults with hypoparathyroidism responded well to recombinant natural human parathyroid hormone, rhPTH (1-84). According to results presented here, the drug reduced the need for large amounts of calcium and vitamin D supplementation.

“Many individuals with hypoparathyroidism are on very high amounts of calcium. Parathyroid hormone is  the logical treatment for this disease, which is characterized by low or absent parathyroid hormoen,” John P. Bilezikian, MD, professor of medicine and pharmacology at the College of Physicians and Surgeons at Columbia University, told Endocrine Today.

Bilezikian and colleagues designed REPLACE — a randomized, double blind, placebo-controlled, phase 3 study to determine whether a recombinant, natural form of human parathyroid hormone (rhPTH [1-84]) could reduce calcium and vitamin D requirements while maintaining normal albumin-corrected total serum calcium concentration.

Of the 134 study patients, 90 were randomly assigned to 50 mcg subcutaneous rhPTH (1-84) (Natpara, NPS) and 44 were assigned to placebo for 24 weeks. If necessary, the treatment dose was increased to 75 mcg or 100 mcg during a 6- to 8-week period. After randomization, calcium and vitamin D supplementations were reduced in stages.

Eighty-four patients in the rhPTH (1-84) group and 37 in the placebo group completed the study.

“When the blood calcium is low, the nervous system becomes very irritable. The neuromuscular irritability can range from paresthesias such as pins and needles to more serious muscular spasms, trouble breathing and even seizures,” Bilezikian said. “For this and other reasons, it can be a dangerous disease.”

Additional adjustments in calcium or vitamin D were allowed to maintain normal serum calcium levels of 8 mg/dL to 9 mg/dL.

Patients were considered “responders” when oral calcium supplementation and active vitamin D metabolite/analog therapy could be decreased by 50% at week 24, while total serum calcium levels were normalized or maintained at levels greater than 7.5 mg/dL.

More than half of patients in the treatment group (53.3%) compared with only 2.3% of those in the placebo group were classified as responders at the end of the 24-week treatment period. The difference in responder rate between the treatment and placebo groups was highly significant (P<.001). The mean dose of oral calcium increased by 5.7% from baseline in the placebo group, but decreased by an impressive 52% in the treatment group (P<.001). In addition, vitamin D therapy was reduced by 30.5% in the placebo group vs. 78.4% in the treatment group (P<.001).

At 24 weeks, 41.1% of the rhPTH(1–84) group achieved complete independence from vitamin D whereas only 2.3% of the placebo group reached this other endpoint of the study (P<.001), Bilezikian said.

“The promise of this drug is to make available the missing natural hormone, namely parathyroid hormone, in those suffering from hypoparathyroidism. The analogy is giving thyroid hormone to individuals with hypothyroidism or insulin to patients with diabetes,” Bilezikian said.

According to Bilezikian, increased blood calcium, was seen uncommonly.

In his own study from Columbia University Medical Center, he said, “In our experience, of all the blood calcium measurements we made over a 4-year period of time, levels were minimally elevated in 1.9% of the first 27 patients who finished our study. Hypercalcemia is unlikely to be an issue with this drug.”

NPS Pharmaceuticals intends to file for formal review of their data on rhPTH (1-84) in hypoparathyroidism to the FDA this November, Bilezikian said. – by Samantha Costa

For more information:

Bilezikian J. Abstract #S18-3. Presented at: the Endocrine Society’s 94th Annual Meeting & Expo; June 23-26, 2012; Houston.

Disclosure: Drs. John Bilezikian, Dolores Shoback, Tamara Vokes, Michael Mannstadt, Bart Clarke all report being an advisory group member for NPS Pharmaceuticals. Dr. Bilezikian is the principal investigator for NPS and Dr. Shoback is an investigator. Drs. Hjalmar Lagast and Roger Garceau are employees of NPS. Dr. Leif Mosekilde reports no relevant financial disclosures.