Horizon Therapeutics, Inc. has announced that two pivotal Phase 3 trials evaluating its lead investigational product candidate, HZT 501, met all primary endpoints.
HZT 501, a novel, proprietary fixed-dose combination product containing ibuprofen and famotidine, demonstrated a statistically significant reduction in the incidence of non-steroidal anti-inflammatory drug (NSAID)-induced upper gastrointestinal (gastric and/or duodenal) ulcers in patients with mild-to-moderate pain when compared to ibuprofen alone.
NSAIDs such as ibuprofen are among the most widely used drugs in the world. However, NSAIDs are associated with a range of adverse side effects, which primarily affect the gastrointestinal (GI) tract. Up to 30 percent of patients taking NSAIDs experience gastrointestinal ulcers and a greater percent suffer from upper GI symptoms (i.e., dyspepsia, heartburn).
"NSAIDs, while highly effective in treating pain and inflammation, often lead to serious safety concerns, including significant gastrointestinal damage," said Timothy P. Walbert, president and chief executive officer, Horizon Therapeutics. "We are committed to bringing this much needed treatment to physicians and patients as quickly as possible and plan on submitting these strong HZT 501 Phase 3 results to U.S. and European regulatory authorities in 2009."
The Registration Endoscopic Study to Determine Ulcer Formation of HZT 501 Compared to Ibuprofen: Efficacy and Safety Study (REDUCE 1 and REDUCE 2) were two randomized, double-blind, controlled trials that enrolled more than 1,500 patients in the United States. The primary efficacy objective of REDUCE-1 was to evaluate HZT 501 in reducing the proportion of patients who develop endoscopically diagnosed gastric ulcers during the 24-week treatment period, as compared to ibuprofen, in patients at risk for NSAID-induced ulcers. The primary objective of REDUCE-2 was to evaluate HZT 501 in reducing the proportion of patients who develop endoscopically diagnosed gastric and/or duodenal ulcers during the 24-week treatment period, as compared to ibuprofen, in patients at risk for NSAID-induced ulcers. The trials were conducted via a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA).
Patients, who had mild-to-moderate pain, including those with osteoarthritis, were randomly assigned, in approximately a 2:1 ratio, to receive HZT 501 (800 mg ibuprofen and 26.6 mg famotidine) or ibuprofen (800 mg) alone orally three times daily for a 24- week treatment period or until patients developed either an endoscopically diagnosed upper gastrointestinal ulcer and/or prohibitive toxicity. Patients received endoscopies at baseline and weeks 8, 16 and 24.
In REDUCE-1, 24-week treatment with HZT 501 resulted in a statistically significant reduction in gastric ulcers versus treatment with ibuprofen alone. In REDUCE-2, 24-week treatment with HZT 501 resulted in a statistically significant reduction in gastric and/or duodenal ulcers versus treatment with ibuprofen alone.
Treatment with both HZT-501 and ibuprofen alone were well tolerated in the studies. The majority were mild to moderate in severity. There were no significant differences between the two treatment groups adverse event or serious adverse event profiles.
"NSAIDs can cause significant gastrointestinal damage, including ulcers of the stomach and duodenum" said Loren Laine, MD, professor of medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California. "These results indicate that HZT-501 can reduce the risk of ulcers, potentially improving the GI safety for patients treated with NSAIDs."