NPS Estimates Gattex Initial Market At $150 Million To $250 Million

Company is seeking a pre-NDA meeting with FDA to discuss mixed top-line results from a Phase III study of the agent in short bowel syndrome.

NPS Pharmaceuticals estimates peak annual sales of its glucagon-like peptide 2 analog Gattex (teduglutide) could hit $250 million if approved by FDA in short bowel syndrome.

"We believe the use of Gattex in SBS not only represents a potential first in class opportunity for a GLP-2 agonist but potentially a new standard of care for this specialty indication," NPS CEO Tony Cole stated during an Oct. 11 conference call announcing top-line Phase III results.

"If approved, we believe there is a potential market opportunity of at least $150 to $250 million in peak annual sales for what we hope will be the first of several additional specialty indications for Gattex."

While SBS is a relatively small market, Cole noted that NPS expects Gattex to be "premium priced," although he declined to give a specific amount.

Revenues of that caliber would be a boon for NPS, as the firm has been weathering a case of financial instability over the past year. In March, company announced it would have to reduce its workforce from 196 to 35 employees, and consolidate operations (¹ (Also see "NPS Downsizes, Seeks Partners To Develop Preos And Teduglutide" - Pink Sheet, 15 Mar, 2007.)).

Gattex could prove to be the company's saving grace, if it can serve as a platform to other indications.

Cole noted that NPS is "also exploring the potential of Gattex to treat a variety of other high value specialty GI disorders, including chemotherapy-induced GI mucositis and necrotizing enterocolitis."

The Phase III SBS study generated mixed data - with patients receiving a high dose of Gattex showing no clinically meaningful benefit - but the firm is moving forward to seek a pre-NDA meeting with FDA to discuss the results before filing the application in mid-2008.

The 83-patient, multi-center, double-blind trial evaluated Gattex compared with placebo in patients with parenteral nutrition (PN)-dependent short bowel syndrome.

Patients were randomized to receive daily subcutaneous injections of 0.05 milligrams or 0.10 milligrams of Gattex per kilogram of body weight or placebo for six months after an evaluation period of three days to eight weeks and a period of stabilization of four to eight weeks. A total of 71 patients completed the study, reflecting a 14.5 percent dropout rate.

The clinical efficacy endpoint of the study was a reduction in PN of at least 20 percent comparing baseline to weeks 16 to 24.

In the patients receiving the lower dose, 45.7 percent (16 out of 35) demonstrated a 20 percent or greater reduction in PN (p-value 0.007), compared to 25 percent (8 out of 32) in the high-dose group (p-value 0.161) and 6 percent (one of 16) in the placebo group.

Two patients gained independence from and discontinued PN by week 20 and a third patient discontinued PN at the end of treatment.

"The study's criteria for conducting the statistical analysis of the primary endpoint required that the results for the high-dose group show statistical significance before the results of the low-dose group could be considered," the company explained in a news release.

While the low dose group reached statistical significance, the high dose arm did not.

"However, given the drug's orphan designation in SBS and the statistically strong (p=0.007) and clinically meaningful findings in the low-dose group, the company intends to meet with the FDA to discuss the path to regulatory approval for Gattex," the firm said.

According to NPS, "there are several hypotheses that may explain the higher response in the low-dose group versus the higher-dose group. One theory is that, at higher doses, GLP-2 suppresses appetite and it is possible that patients on the higher dose consumed fewer calories from food and thus did not decrease their PN regimens."

"A second hypothesis is that GLP-2 exerts various dose-dependent effects and may act by increasing nutrient absorption at low doses while higher doses of GLP-2 may have a greater effect on mucosal and epithelial regeneration."

In addition to Gattex, the company has another orphan drug in development. The firm is investigating Preos (parathyroid hormone [rDNA origin] for injection) in treatment of hypoparathyroidism in Phase II proof-of-concept trials. The drug received an "approvable" letter for osteoporosis, as well.

NPS recently announced that it would end its longstanding partnership with AstraZeneca to develop drugs targeting metabotropic glutamate receptors, and that AstraZeneca would pay the firm $30 million to take over the program (² (Also see "AstraZeneca Will Take Over mGluR Program From NPS Pharmaceuticals For $30 Million" - Pink Sheet, 9 Oct, 2007.)).

-Brooke McManus ([email protected])