PALO ALTO, Calif., March 27 /PRNewswire/ -- Horizon Therapeutics, Inc., a privately held biopharmaceutical company, today announced that it has initiated its phase 3 trial program for HZT-501, a “GI-friendly” prescription NSAID product candidate for mild-to-moderate pain relief. Enrollment has been opened and the first patient has initiated dosing.
The two phase 3 studies for HZT-501 are being conducted via a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA). The SPA agreement indicates that if the trials successfully meet their primary endpoint, the data will provide support for an efficacy claim in a marketing application to the FDA.
HZT-501 is a proprietary formulation of the world’s most prescribed non-steroidal anti-inflammatory drug (NSAID) ibuprofen, combined with the most potent H2 receptor antagonist famotidine, in a single pill. HZT-501 is specifically designed to provide pain relief while reducing stomach acidity during the peak time of risk for ulceration. In a randomized pilot clinical study published in The New England Journal of Medicine (Taha, et. al May 1996), famotidine was demonstrated to significantly reduce the incidence of gastric and duodenal ulcers vs. placebo when administered together with NSAIDs.
“Given the well known gastrointestinal side effects of NSAIDs, there is a clear need for a product like HZT-501,” said Dr. Alan Kivitz, M.D., Altoona Arthritis and Osteoporosis Center, and a principal investigator in one of the phase 3 trials. “Combining two well known proven compounds into one pill could be an effective and promising solution to treat the millions of patients in need of pain relief. HZT-501 has the potential to enhance patient adherence to their treatment regimen while assuring on-board GI protection.”
About the Phase 3 Clinical Program
The phase 3 clinical program for HZT-501 is comprised of two trials involving a total of 1,200 patients with mild-to-moderate pain, including patients with osteoarthritis. Horizon Protocols HZ-CA-301 and HZ-CA-303 will evaluate the efficacy and safety of HZT-501 with the primary efficacy endpoint being reduction in the risk of development of ibuprofen-associated upper gastrointestinal ulcers in patients who require the use of ibuprofen.
The clinical trials are multi-center, randomized, and include an active control treatment. Trial participants will receive study medication for up to 24 weeks. Both studies will be conducted in the United States.
“HZT-501 is the first product in Horizon’s pipeline to enter a phase 3 trial and is a major milestone for the company,” said George F. Tidmarsh, M.D., Ph.D., co-founder and chief executive officer of Horizon Therapeutics. “We hope to offer a unique treatment solution to millions of people who suffer from chronic and acute pain.”
Proof-of-concept
In the May 30, 1996 edition of the New England Journal of Medicine, an article, “Famotidine for the Prevention of Gastric and Duodenal Ulcers Caused by Non-steroidal Anti-inflammatory Drugs” was published by Taha, et. al. The study was a randomized, controlled trial including 285 arthritis patients. The primary endpoint was the measurement of the cumulative incidence of endoscopically diagnosed gastric and duodenal ulcers at 4, 12 and 24 weeks in patients treated with an NSAID alone versus those treated with NSAID plus a total daily dose of either 40mg or 80mg of famotidine.
The cumulative incidence of gastric ulcers was 20% in the NSAID-alone group and 8% in the 40-mg BID (twice daily) famotidine plus NSAID group (p = 0.03). The cumulative incidence of duodenal ulcers was 13% in the NSAID- alone group and 2% in the 40-mg BID famotidine plus NSAID group (p = 0.01). There were also significantly lower rates of gastric and duodenal ulceration when analyzed separately and when combined (28% for the NSAID-alone group vs. 11% for the 40-mg BID famotidine plus NSAID group; p = 0.003).
About the Pain Market
HZT-501 targets the widespread product void in the mild-to-moderate pain market left by COX-2 inhibitors such as Vioxx(R), which have either been taken off the market or are being prescribed less frequently due to elevated cardiovascular risk. In 2005, the U.S. NSAID market grew over 20 percent to 73 million prescriptions. Over 26 million ibuprofen prescriptions are now written annually in the U.S. alone.
However, while commonly prescribed to treat pain, NSAIDs have been linked to serious gastrointestinal (GI) side effects in up to 25 percent of all chronic arthritis patients. NSAID-induced GI toxicity causes an estimated 16,000 deaths and more than 100,000 hospitalizations annually in the United States. Despite this, studies have shown that as low as 30% of high-risk patients are commonly co-prescribed a gastro-protective agent in combination with their NSAID to prevent or relieve side effects. In addition, patient adherence to a regimen of separate GI protective and pain medications has also been shown to be poor.
About Horizon Therapeutics
Horizon Therapeutics, Inc. is a late stage biopharmaceutical company focused on the rapid development and commercialization of therapeutic treatments for mild-to-moderate pain management. The Company is building a novel portfolio of therapies through innovative combinations of approved pharmaceutical products that seek to improve safety, efficacy, and patient compliance. Its lead product candidate, HZT-501, entered phase 3 trials in the first quarter of 2007. In addition to HZT-501, Horizon has a pipeline of follow-on pain combination products in earlier stages of development. For more information visit www.horizontherapeutics.com .
Horizon Therapeutics, Inc.
CONTACT: Angela Bitting for Horizon Therapeutics, +1-925-202-6211, ora.bitting@comcast.net
Web site: http://www.horizontherapeutics.com//
