NPS Pharmaceuticals Inc. on Thursday presented data from the TOP study of Preos, for vertebral fractures in postmenopausal women, at the American College of Rheumatology meeting. The drug is on file with the FDA, but serum calcium levels in the trial had investors worried about how the drug would stack up against Eli Lilly and Co.'s Forteo, already on the market.

NPS' stock fell $1.22 Thursday, or 6.7 percent, to close at $16.88. It traded as low as $16 during the day, and a total of 3 million shares exchanged hands, about four times the company's average volume.

The stock (NASDAQ:NPSP) on Friday fell 13 cents to close at $16.75.

NPS reported early TOP data in the spring. The company hopes to file a new drug application with the FDA by the end of the year. Roskilde, Denmark-based Nycomed Group has European rights through a deal potentially valued at more than $90 million. (See BioWorld Today, March 31, 2004, and April 22, 2004.)

Thursday's data from the 18-month TOP (Treatment of Osteoporosis with Parathyroid Hormone) study, involved about 2,600 postmenopausal osteoporotic women randomized to receive a daily subcutaneous injection of 100 micrograms of Preos or placebo, in addition to daily calcium and vitamin D supplements. The women averaged 64 years of age.

At baseline, the mean serum calcium level for the patients was 9.7 milligrams per deciliter (mg/dL), and 9 percent of patients had levels greater than 10.2 mg/dL. The women were not specifically tested for either hyperparathyroidism or a vitamin D deficiency, both of which can affect serum calcium levels, the company said. The mean spine, total hip and femoral neck bone mineral density (BMD) T scores at baseline were minus 3.0, minus 1.9 and minus 2.2, respectively, and 19 percent of patients had a prevalent vertebral fracture.

NPS, of Salt Lake City, previously reported that the administration of Preos resulted in a new or worsened vertebral fracture risk reduction of 59 percent in all patients who received at least one dose of drug or placebo. At the conference, the company included data from patients who took at least 75 percent of their prescribed doses and had no other protocol violations. In those patients, the new vertebral fracture incidence (VFI) was lower in the Preos group than the placebo group (1.1 percent vs. 3.3 percent, respectively), and Preos-treated patients had a relative fracture risk reduction (RFRR) of 66 percent.

Data also showed that in those with a prevalent vertebral fracture, Preos decreased new VFI from 8.4 percent to 2.6 percent, which translated to a 69 percent RFRR. In those without a prevalent vertebral fracture, Preos decreased new VFI from 2.2 percent to about 0.8 percent, which represented a 63 percent RFRR.

Over the course of the study, a total of 21 percent of Preos-treated patients and 3 percent of placebo patients experienced a measurement of baseline serum calcium at greater than 10.7 mg/dL, and 0.7 percent of Preos-treated patients discontinued the study due to increased serum calcium.

It was that 21 percent that worried investors, particularly in comparison with serum calcium levels seen in Forteo trials. But Soham Pandya, analyst with Susquehana Financial Group LLLP in New York, is behind the product.

"It's difficult to compare across studies," he said. In his research note on the conference presentation, Pandya wrote that Susquehana expects "that any differences in hypercalcemia compared to the 11 percent noted with Lilly's Forteo will largely be explained by analysis of baseline patient characteristics, as the TOP study enrolled some patients that had abnormalities in calcium metabolism, such as patients with primary and secondary hyperparathyroidism. We note that the baseline serum calcium levels in patients at study entry were higher in the TOP study (9.7 mg/dL) compared to the approval study for Forteo (9.2 mg/dL)."

Speaking on Preos overall, Pandya told BioWorld Today that "we think it's an approvable drug," adding that the market for anabolic agents is growing.

Lilly's Forteo, approved in November 2002, is indicated for postmenopausal women with osteoporosis who are at high risk for fracture. It's also indicated to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. The product brought Lilly $58.1 million in the third quarter, with $47.6 million coming from the U.S.

When asked if Preos could take a similar chunk of the market, Pandya said: "Certainly. That's our assumption."

NPS also is developing teduglutide, which began a Phase III trial in short-bowel syndrome in the spring. The product also is in Phase II testing for Crohn's disease. Teduglutide is an analogue of glucagon-like peptide-2, a naturally occurring hormone that regulates proliferation of the cells lining the small intestine.

There also is Sensipar (cinacalcet), partnered with Thousand Oaks, Calif.-based Amgen Inc., already on the market. The drug was approved in March for hyperparathyroidism in patients with chronic kidney disease on dialysis and for hypercalcemia in those with parathyroid carcinoma.

In general, Pandya is upbeat on NPS. He wrote that "in our view, investors are underappreciating the value of [NPS'] assets, particularly the fact that Preos can participate in an expanding market for anabolic agents for the treatment of osteoporosis."