Hypoparathyroidism Drug Shows Promise in Phase 3 Trial

Laird Harrison

November 09, 2011

November 9, 2011 — An experimental synthetic replacement for human parathyroid hormone, NPSP558, showed promise in a phase 3 trial, NPS Pharmaceuticals, the drug's manufacturer, announced November 7.

"In an intent-to-treat analysis, 53 percent (48/90) of NPSP558-treated patients achieved the primary endpoint versus 2 percent (1/44) of placebo-treated patients (p<0.0001)," the company said in a press release. "The primary efficacy endpoint was defined as a 50 percent or greater reduction in oral calcium supplementation and active vitamin D therapy and a total serum calcium concentration that was normalized or maintained compared to baseline after 24 weeks of treatment."

"It was a small study, but the difference between those receiving the drug and those receiving the placebo was impressive," E. Michael Lewiecki, MD, director of the New Mexico Clinical Research and Osteoporosis Center in Albuquerque, told Medscape Medical News. Dr. Lewiecki was not involved in the study.

Hypoparathyroidism is rare and is the only endocrine disorder for which a replacement hormone has not been approved by the US Food and Drug Administration.

Clinicians typically manage the symptoms with large doses of oral calcium and active vitamin D supplementation, but these therapies can cause long-term health complications, such as kidney damage.

"Particularly for those patients who have trouble controlling their calcium levels, this could be very good," said Dr. Lewiecki, who is also a clinical assistant professor of medicine at the University of New Mexico.

NPSP558 is a bioengineered form of human parathyroid hormone (rhPTH) 1-84. The drug has been marketed as Preotact since 2006 for the treatment of osteoporosis in postmenopausal women who are at high risk for fractures.

In 2007, the US Food and Drug Administration granted orphan drug status for NPSP558 for the treatment of hypoparathyroidism.

To test NPSP558 in this disease setting, the company recruited 134 patients at more than 30 sites in North America and Europe.

The study consisted of an average 10-week screening and stabilization period, followed by a 24-week treatment period in which patients were randomly assigned in a 2:1 ratio to receive either 50 μg NPSP558 once daily or placebo. If needed, patients then received a stepwise up-titration to a dose of 75 μg NPSP558, and then, if necessary, to 100 μg NPSP558 during a 6- to 8-week period.

At week 24, 43% (36/84) of the NPSP588-treated patients were able to stop active vitamin D therapy and required a calcium supplementation dose of 500 mg/day or less, while maintaining stabilized serum calcium, compared with 5% (2/37) of placebo-treated patients (P < .0001).

Thirteen of the 134 participants discontinued the study early, of whom 7 patients were receiving placebo and 6 were receiving NPSP558. Overall, the incidence of adverse events and serious adverse event were similar among both groups, the company reported. No specifics were provided about adverse events.

"These positive results from our Phase 3 REPLACE study are an important milestone and bring us one step closer to our goal of providing hypoparathyroidism patients with a much-needed replacement therapy," said Francois Nader, MD, president and chief executive officer of NPS Pharmaceuticals, in a news release. "Based on these results we expect to file for [US Food and Drug Administration] approval of NPSP558 in 2012."

NPSP558, which is delivered via injection, is not the only replacement being tested for parathyroid hormone: Also in the pipeline are drugs that could be taken orally or through a transdermal patch.

"Even though this is a great first step, if [drugs with] these other delivery systems get approved, that's going to be even more attractive to these patients," Dr. Lewiecki said.

Dr. Lewiecki is an investigator and consultant for Eli Lilly.