Staff Writer

NPS Pharmaceuticals Inc. said partner GlaxoSmithKline plc prematurely halted a Phase II trial of osteoporosis drug Ronacaleret (SB-751689) after a planned interim analysis showed a lack of efficacy.

NPS executives could not be reached for comment, but the Bedminster, N.J.-based company said in a regulatory filing that the decision is not the result of any unexpected safety signals or concerns.

The Phase II trial was a randomized, double-blind, placebo and active-controlled, dose-ranging study in post-menopausal women with osteoporosis. The interim analysis occurred six months into the 12-month trial and included a futility analysis. Data were reviewed by GSK management, internal committees and external experts.

In a letter to trial investigators, GSK said it observed a lack of efficacy in the primary endpoint of lumbar spine bone mineral density. Additionally, Ronacaleret resulted in statistically significant decreases in total hip bone mineral density relative to placebo, although that was deemed not clinically relevant, and no unexpected safety risks were observed.

Even so, GSK said findings likely preclude further development of the compound for osteoporosis. Under a 1993 deal between NPS and SmithKline Beecham (now GSK), NPS has received $26.1 million in fees, expenses, milestone payments and equity investments. The company said it gets to keep that money but noted that GSK hasn't communicated any decisions regarding the future of the deal.

Ronacaleret is a calcilytic - an oral, small-molecule antagonist of the calcium-sensing receptors on the surface of the parathyroid gland. In preclinical studies, the compound stimulated the release of parathyroid hormone (PTH), increasing bone mineral density and stimulating new bone formation.

Most marketed osteoporosis treatments, like Fosamax (alendronate sodium, Merck & Co. Inc.), slow down the resorption of bone but don't build new bone. An exception is Eli Lilly and Co.'s recombinant PTH drug Forteo (teriparatide). But since PTH also regulates calcium homeostasis, Forteo has been associated with hypercalcemia.

Hypercalcemia also posed a problem for NPS' own recombinant PTH drug, Preos, which received an approvable letter in 2006 due to concerns about the side effect. (See BioWorld Today, March 13, 2006, and May 4, 2006.)

NPS is seeking a partner to complete development of Preos for osteoporosis in the U.S., and the drug is in Phase II trials for hypoparathyroidism. Meanwhile, NPS and partner Nycomed Group gained an osteoporosis approval in Europe, where the drug is marketed as Preotact. (See BioWorld Today, April 22, 2004.)

Zurich, Switzerland-based Nycomed also is NPS' partner on Gattex (teduglutide), which last year failed a Phase III trial in short bowel syndrome. Yet the drug, an analogue of glucagon-like peptide-2, demonstrated efficacy at the lower dose, and the partners are conducting a second Phase III trial. (See BioWorld Today, Oct. 12, 2007, and Nov. 1, 2007.)

NPS has Phase II studies of Gattex under way in Crohn's disease and is conducting preclinical work in chemotherapy-induced gastrointestinal mucositis for patients with cancer and necrotizing enterocolitis for preterm infants.

In addition to Preotact/Preos and Gattex, NPS has an early stage central nervous system drug and partnered programs ranging from Phase I to marketed products.

Investors shaved a bit of value off NPS due to the setback in the GSK-partnered osteoporosis program. Shares (NASDAQ:NPSP) fell $1.05, or 13 percent, to close at $7.28 on Friday. Yet the stock has more than doubled since April and still is trading near its 52-week high.