Study results show risk factors for ulcer development among NSAID users

Horizon Therapeutics Inc., a privately held biopharmaceutical company, recently presented an analysis from 2 pivotal phase 3 trials (REDUCE-1 and REDUCE-2) evaluating its lead investigational compound HZT-501, a combination of ibuprofen with high-dose famotidine, PRNewswire reported.

The analysis, which was designed to identify risk factors for the development of non-steroidal anti-inflammatory drug (NSAID)-associated ulcers, was presented at the 74th American College of Gastroenterology (ACG) Annual Scientific Meeting.

“Upper gastrointestinal tract ulcers develop commonly in people taking NSAIDs and can occur without warning symptoms. Historically, there have been limited data identifying the factors that predict an increased risk of finding ulcers in NSAID users,” said Loren Laine, MD, University of Southern California Keck School of Medicine and lead investigator. “Data collected from the REDUCE-1 and REDUCE-2 trials provide insight into these risk factors. The statistically significant independent risk factors included the use of the NSAID ibuprofen without the histamine-2 receptor antagonist famotidine, previous ulcer disease and older age.”

The two phase 3 clinical trials, REDUCE-1 and REDUCE-2 (Registration Endoscopic Studies to Determine Ulcer Formation of HZT-501 Compared to Ibuprofen: Efficacy and Safety Studies), conducted via a Special Protocol Assessment (SPA) with FDA, were randomized, double-blind, controlled trials that enrolled more than 1,500 patients with mild-to-moderate pain. Patients were randomly assigned, in approximately a 2:1 ratio to receive either HZT-501 (800 mg ibuprofen and 26.6 mg famotidine) or the NSAID ibuprofen (800 mg) alone orally three times daily for a 24-week treatment period or until patients developed either an endoscopically diagnosed upper gastrointestinal (GI) ulcer and/or prohibitive toxicity.

Results showed that patients with mild-to-moderate pain treated with HZT-501 developed approximately 50% fewer NSAID-associated upper GI ulcers compared to patients treated with ibuprofen alone.

The statistical analysis looked at the combined 1,382 patients studied in the REDUCE-1 and REDUCE-2 primary study populations (HZT-501, N=930; ibuprofen, N=452). The predefined population for primary analyses of upper GI ulcers was all patients with at least one on-study endoscopy (EGD). The life table analysis estimate showed that fewer patients taking HZT-501 developed upper GI ulcers than those taking ibuprofen alone after 24 weeks (14.1% versus 26.5%, P

Baseline erosions (GI erosions noted on baseline endoscopy at the start of the study 1.15 (0.82, 1.62)

“By identifying these independent risk factors, physicians may be able to better assess a patient’s risk for NSAID-associated GI toxicity,” said Timothy P. Walbert, president and chief executive officer of Horizon Therapeutics.