Horizon Pharma Announces FDA Approval of DUEXIS® (ibuprofen/famotidine) for the Relief of the
Signs and Symptoms of Rheumatoid Arthritis and Osteoarthritis and to Decrease the Risk of
Developing Upper Gastrointestinal Ulcers
NORTHBROOK, Ill. –
April 25, 2011 –
Horizon Pharma, Inc., a biopharmaceutical company developing
and commercializing innovative medicines to target unmet therapeutic needs in arthritis, pain and
inflammatory diseases, announced today that the U.S. Food and Drug Administration (FDA) has approved DUEXIS®
, (ibuprofen/famotidine) a novel tablet formulation containing a fixed-dose combination of
ibuprofen (800 mg) and famotidine (26.6 mg). The FDA approval was supported by data from the pivotal
REDUCE-1 and REDUCE-2 studies, which showed patients taking DUEXIS experienced significantly
fewer upper gastrointestinal ulcers compared to patients receiving ibuprofen alone.
“We look forward to providing DUEXIS to the many patients suffering from osteoarthritis and rheumatoid
arthritis, as it provides a new treatment option for those who may be at risk for upper gastrointestinal
ulcers stemming from chronic NSAID use,” said Timothy P. Walbert, chairman, president and chief
executive officer of Horizon Pharma. “The approval of DUEXIS is a transformative event for Horizon
Pharma, representing our first U.S. approval. We would like to thank the patients and clinical investigators
who participated in the pivotal REDUCE-1 and REDUCE-2 trials.”
DUEXIS was studied in more than 1,500 patients with mild-to-moderate pain or arthritis. The primary
endpoint of the REDUCE-1 study was the reduction in incidence of gastric ulcers during the six month
treatment period. The primary endpoint of the REDUCE-2 study was the reduction in incidence of upper
gastrointestinal (defined as gastric and/or duodenal) ulcers during the six month treatment period. In
REDUCE-1, DUEXIS demonstrated a statistically significant reduction in the incidence of gastric ulcers
versus treatment with ibuprofen alone (8.7% versus 17.6%). In REDUCE-2, DUEXIS demonstrated a
statistically significant reduction in the incidence of upper gastrointestinal ulcers versus treatment with
ibuprofen alone (10.5% versus 20.0%).
The most common adverse reactions (≥1% and greater than ibuprofen alone) were nausea, diarrhea,
constipation, upper abdominal pain and headache. Overall, the discontinuation rate in the REDUCE-1
and REDUCE-2 studies due to adverse events for patients receiving DUEXIS and ibuprofen alone were
“The clinical data showed that DUEXIS helped reduce the incidence of upper gastrointestinal ulcers, which
should be welcome news for physicians and patients concerned about the gastrointestinal impact of
NSAID use,” said Michael Schiff, M.D., Clinical Professor of Medicine at the University of Colorado School
of Medicine, Rheumatology Division. “In my view, DUEXIS will allow more people access to the benefits
of ibuprofen, while reducing the significant GI risk associated with its use.”
Important Safety Information
Cardiovascular and Gastrointestinal Risks
Ibuprofen, a component of DUEXIS, may increase the risk of serious cardiovascular (CV)
thrombotic events, myocardial infarction, and stroke, which can be fatal. Risk may increase
with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular
disease may be at greater risk.
DUEXIS is contraindicated for the treatment of perioperative pain in the setting of coronary
artery bypass graft (CABG) surgery.
NSAIDs, including ibuprofen, a component of DUEXIS, increase the risk of serious
gastrointestinal (GI) adverse reactions including bleeding, ulceration, and perforation of the
stomach or intestines, which can be fatal. Reactions can occur at any time without warning
symptoms. Elderly patients are at greater risk.
DUEXIS should not be given to patients who have experienced asthma, urticaria, or allergic reactions after
taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylaxis with NSAIDs have been reported in such
patients. DUEXIS is contraindicated for the treatment of perioperative pain in the setting of coronary
artery bypass graft (CABG) surgery.
DUEXIS is contraindicated in patients in late stages of pregnancy.
DUEXIS should not be administered to patients with a history of hypersensitivity to other H2-receptor
antagonists. Cross sensitivity with other H2-receptor antagonists has been observed.
When active and clinically significant bleeding from any source occurs in patients receiving DUEXIS, the
treatment should be withdrawn.
NSAIDs, including ibuprofen, which is a component of DUEXIS tablets, can lead to onset of new
hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased
incidence of CV events.
Fluid retention and edema have been observed in some patients taking NSAIDs. DUEXIS should be used
with caution in patients with fluid retention or heart failure.
Reports suggest that ibuprofen, a component of DUEXIS, may diminish the antihypertensive effect of
ACE-inhibitors. This interaction should be given consideration in patients taking DUEXIS concomitantly
As with other NSAIDs, the concurrent use of aspirin and DUEXIS may increase the risk of adverse events
Long-term administration of NSAIDs, including ibuprofen, which is a component of DUEXIS tablets, has
resulted in renal papillary necrosis and other renal injury.
If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur,
DUEXIS should be discontinued.
Bleeding has been reported when ibuprofen and other NSAIDs have been administered to patients on
coumarin-type anticoagulants, prescribers should be cautious when administering ibuprofen to patients on
anticoagulants. Please see Full Prescribing Information for DUEXIS at
DUEXIS is a novel fixed-dose tablet combining the one of the world's most prescribed NSAIDs, ibuprofen,
with the most potent H2-antagonist, famotidine (800 mg/26.6 mg), in a single pill. Ibuprofen has proven
anti-inflammatory and analgesic properties, whereas famotidine reduces the stomach acid secretion that
can cause gastric and duodenal ulceration. By combining ibuprofen and famotidine into a single product,
it is believed that ibuprofen's gastrointestinal safety profile will be improved without altering its ability to
reduce pain and inflammation.
DUEXIS is indicated for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis and to
decrease the risk of developing upper gastrointestinal ulcers, which in the clinical trials was defined as a
gastric and/or duodenal ulcer, in patients who are taking ibuprofen for those indications. The clinical trials
primarily enrolled patients less than 65 years of age without a prior history of gastrointestinal ulcer.
Controlled trials do not extend beyond 6 months.
DUEXIS will be available to U.S. physicians in the second half of this year. For more information,
including full prescribing information, please visit www.DUEXIS.com.
Horizon submitted a Marketing Authorization Application (MAA) to the European Medicines Association
(EMA) for DUEXIS in October 2010.
About the Arthritis Market
Osteoarthritis (OA) is a degenerative joint disease caused by the breakdown and eventual loss of the
cartilage of one or more joints. It is the most common form of arthritis and the most common cause of
chronic pain, affecting more than 150 million individuals worldwide and 27 million Americans. OA is
caused by various factors, including older age, being overweight, joint injury or stress, heredity and
muscle weakness. OA commonly affects the hands, spine or large weight-bearing joints, such as the hips
Rheumatoid arthritis (RA) is a chronic disease, mainly characterized by inflammation of the lining, or
synovium, of the joints. It can lead to long-term joint damage, resulting in chronic pain, loss of function
According to the Arthritis Foundation, a leading non-profit arthritis research advocacy group, arthritis
affects nearly 46 million people in the U.S. With the aging of the U.S. population, the prevalence of
arthritis is expected to rise by approximately 40% by 2030, impacting 67 million people in the U.S.
NSAIDs are very effective at providing pain relief associated with OA and RA; however, there are
significant upper GI-associated adverse events which can result from such treatments. Significant GI side
effects, including serious ulcers, afflict up to approximately 25 percent of all chronic arthritis patients
treated with NSAIDs for three months, and OA and RA patients are two to five times more likely than the
general population to be hospitalized for NSAID-related GI complications. It is estimated that NSAID-
induced GI toxicity causes over 16,500 related deaths in OA and RA patients alone and over 107,000
hospitalizations for serious GI complications each year in the U.S. About Horizon Pharma
Horizon Pharma, Inc. is a biopharmaceutical company that is developing and commercializing innovative
medicines to target unmet therapeutic needs in arthritis, pain and inflammatory diseases. For more
information, please visit www.horizonpharma.com. Forward Looking Statements
This press release contains forward-looking statements regarding the potential for DUEXIS to treat
osteoarthritis and rheumatoid arthritis and to reduce the risk of developing ibuprofen-induced
gastrointestinal ulcers, the ability of DUEXIS to allow greater patient access to ibuprofen, and the timing of
DUEXIS’s availability to physicians. Actual results may differ materially from those in these forward-
looking statements as a result of various factors, including, but not limited to, risks regarding the
company’s ability to commercialize products successfully, whether physicians will prescribe and patients
will use DUEXIS, once available, and competition in the market for DUEXIS. For a further description of
these and other risks facing the company, please see the risk factors described in the company’s
Registration Statement on Form S-1 that was originally filed with the United States Securities and
Exchange Commission on August 3, 2010, and the amendments thereto, including those factors
discussed under the caption “Risk Factors” in those filings. Forward-looking statements speak only as of
the date of this press release, and the company undertakes no obligation to update or revise these
statements, except as may be required by law.
Robert J. De Vaere
Executive Vice President and Chief Financial Officer [email protected]
(312) 550-8138 [email protected]
Curriculum vitae Univ.-Prof. Dr. Andreas Villunger Research Institution: Medical University of Innsbruck, Biocenter, Division of Developmental Immunology, Innrain 80, 6020 Innsbruck, Austria E-mail: [email protected]; http://www.apoptosis.at Personal Data: Date and place of birth: August 5th, 1967 in Innsbruck, Austria Sex: Male; Soc.Sec.Nr.: 2369-050867; Citizensh
Information for consumers Danielle B ARDELAY (International Society of Drug Bulletins) Please do not quote or publish without the permission of the author. Paper prepared for delivery at the conference on European Integration and Health Care Systems: A Challenge for Social Policy . A conference organised during the Belgian Presidency of the European The recent stir over the po