Hormone replacement therapy Natpara appears effective: FDA review

By Toni Clarke

WASHINGTON (Reuters) - NPS Pharmaceuticals Inc's hormone replacement therapy Natpara appears effective, though data from one clinical trial site was excluded due to manufacturing violations, according to a preliminary report by the U.S. Food and Drug Administration.

The report, posted on Wednesday on the FDA's website, comes two days ahead of a meeting of outside advisers to the agency who will discuss the drug and recommend whether it should be approved. The FDA reviewer said serious adverse events were similar between the treatment group and the placebo group.

Natpara is designed to treat hypoparathyroidism, a condition in which the body's parathyroid gland does not secrete enough parathyroid hormone (PTH). The hormone works with vitamin D to regulate body calcium.

Low levels of PTH can cause tingling in the fingers and toes, muscle spasms, fatigue, muscle aches, hair loss, dry skin, headaches, mood swings and memory problems.

The condition can be caused by congenital disorders or surgery and is currently treated with high doses of calcium and vitamin D. Natpara is a bioengineered version of the hormone.

About 180,000 people globally suffer from hypoparathyroidism, according to NPS. In about 40% of cases, the condition cannot be controlled with calcium and vitamin D.

That uncontrolled population is what NPS initially plans to target and it consists of about 20,000 patients in the United States.

Data from a late-stage clinical trial showed 53% of patients treated with Natpara were able to reduce their calcium and vitamin D supplements by 50% or more, compared with 2% of placebo-treated patients.

By week 24, 43% of patients treated with Natpara were able to stop vitamin D therapy and required 500 mg a day or less of calcium, compared with only 5% of patients treated with placebo.

Alan Carr, an analyst at Needham, said in a research note on Monday that he expected a favorable advisory committee vote given the need for new treatments, positive clinical trial results and the "straightforward hormone replacement strategy."

The FDA plans to ask its advisers how concerned they are with the risk of hypercalcemia or hypocalcemia. The agency is also seeking input on the potential risk of osteosarcoma, or bone cancer, with long-term use of the drug.

A heightened risk of osteosarcoma is associated with a similar drug, Forteo, which is made by Eli Lilly & Co and approved to treat osteoporosis. Forteo carries a black box warning on the potential risk of osteosarcoma.

In a two-year rat study, high doses of Natpara were also associated with an increased risk of osteosarcoma. The risk all but disappeared when the drug was given in low doses.

Even so, the FDA reviewer said, the data "does not suggest a negligible risk for developing bone tumors in humans at clinical exposure levels."

The drug was approved in Europe in 2006 to treat osteoporosis in post-menopausal women at high risk for fractures under the trade name Preotact. Regulators noted the osteosarcoma risk and said that until further clinical data became available treatment should not be continued beyond 24 months.

Preotact was recently withdrawn. NPS said the drug was not commercially viable for osteoporosis. The company plans to file for approval of Natpara in Europe later this year.

"It remains to be seen whether the FDA would put a black box for osteosarcoma," Eun Yang, an analyst at Jefferies, said in a research note on Monday. A black box or treatment duration limitations "could have potential impact on commercial uptake, if approved," Yang added.

The FDA is scheduled to make its decision on whether to approve the drug by October 24th.

(c) Copyright Thomson Reuters 2014. Click For Restrictions - http://about.reuters.com/fulllegal.asp