NPS Reports Successful GATTEX Extension Study
NPS Pharmaceuticals reported positive top-line results from a 28-week blinded Phase 3-extension study of GATTEX (teduglutide) for short bowel syndrome (SBS) patients who are dependent upon parenteral nutrition (PN). The extension study enrolled 65 of the 71 patients (91%) who had completed a 24-week randomized Phase 3 study that evaluated low-dose GATTEX (0.05 mg/kg/day) and high-dose GATTEX (0.10 mg/kg/day) versus placebo.
The primary objective of the Phase 3 extension study was to evaluate the long-term safety and tolerability of daily GATTEX dosing for up to 52 weeks (24-week Phase 3 study and 28-week extension study). Overall, both doses of GATTEX were safe and generally well-tolerated, with no statistical differences in the incidence rate of adverse events or serious adverse events among the treatment groups when compared to placebo-treated patients in the Phase 3 study, with the exception of injection site reactions, which were higher in the high-dose GATTEX dose. A number of efficacy measures were also included as a secondary endpoint of the extension study. The company expects full results from the Phase 3-extension study to be presented at a future medical meeting.
Key efficacy findings included:
-- Sixty-eight percent (68%) of the 25 patients who had received low-dose GATTEX therapy and continued on low-dose GATTEX, and fifty-two percent (52%) of the 27 patients who had received high-dose GATTEX therapy and continued on high-dose GATTEX achieved a 20% or greater reduction in PN after a total of 52 weeks of therapy.
-- Patients treated with low-dose GATTEX demonstrated a mean 51% reduction in PN volume from pretreatment baseline to the end of 52 weeks of therapy (p< 0.001) and those treated with high-dose GATTEX experienced a mean 24% reduction (p< 0.001).
-- Six out of six (100%) patients who had previously received placebo in the Phase 3 study and were randomized to low-dose GATTEX therapy, and two out of seven (29%) patients who had previously received placebo in the Phase 3 study and were randomized to high-dose GATTEX therapy, achieved a 20% or greater reduction in PN after a total of 28 weeks of therapy in the extension study.
-- The two low-dose patients and one high-dose patient who were able to discontinue PN in the Phase 3 study remained off PN after 52 weeks of GATTEX therapy.
Bernard Messing, M.D., Head of the Division of Gastroenterology and Nutrition Support at Hopital Lariboisiere-St. Lazare, Paris, stated: "These data support and expand upon previous clinical findings that showed low-dose GATTEX to be a safe and effective potential therapy for short bowel syndrome patients dependent on Parenteral Nutrition. This study provides interesting and very promising results, as improvement of this debilitating chronic disease associated with severe intestinal failure is so difficult to achieve with current treatment options."
Francois Nader, M.D., chief executive officer-elect, stated: "We are very pleased with these results, which reinforce our belief that GATTEX may be a potential new standard of care for SBS. The consistency of these data with the previously reported Phase 3 results is encouraging and we look forward to presenting the full data sets for both studies at upcoming medical meetings. We continue to communicate with FDA and work with our partner Nycomed to complete the design of the confirmatory Phase 3 study, which we expect to initiate in the third quarter of this year."
Phase 3-Extension Study Design
The extension study enrolled 65 of the 71 patients (91%) patients who had previously completed a Phase 3 clinical trial that evaluated low-dose GATTEX (0.05 mg/kg/day), high-dose GATTEX (0.10 mg/kg/day) and placebo for PN-dependent SBS patients. Patients who were already receiving GATTEX in the Phase 3 study continued on their dose for an additional 28 weeks for a total of 52 weeks of therapy. Patients who were receiving placebo in the initial Phase 3 clinical study were randomized in the blinded extension study to receive either a low dose of GATTEX (0.05 mg/kg/day) or a high dose of GATTEX (0.10 mg/kg/day) for 28 weeks of therapy.
Previously Reported Phase 3 Results
In October 2007, NPS reported positive top-line results from the company's Phase 3 study of GATTEX in which 83 patients with short bowel syndrome (SBS) received either a low dose of GATTEX (0.05 milligrams/kilogram/day), a higher dose (0.10 mg/kg/day) or placebo. The clinical efficacy endpoint of the study was a reduction in PN of at least 20% comparing baseline to weeks 20 to 24, measured as a graded response to capture reductions up to 100%. In an intent-to-treat analysis, forty-six percent (46%) of patients receiving the lower dose of GATTEX (N=35) responded and achieved a significant reduction in PN compared to placebo (p=0.007). Twenty-five percent (25%) of patients receiving the higher dose of GATTEX (N=32) responded and showed a trend in the difference between the treatment group and placebo, but this did not reach statistical significance (p=0.161). Two low-dose patients gained independence from and discontinued PN by week 16 and a third high-dose 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. 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 met with the FDA to discuss the regulatory pathway for GATTEX.