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Horizon Pharma, Inc. Release: Annals of the Rheumatic Diseases Publishes Pivotal Phase 3 Study Demonstrating Efficacy and Safety of RAYOS(R) (Delayed-Release Prednisone) in Combination With DMARD Therapy in Rheumatoid Arthritis Patients

5/7/2012 8:37:35 AM

DEERFIELD, IL--(Marketwire - May 07, 2012) - Horizon Pharma, Inc. (NASDAQ: HZNP) today announced that the Annals of the Rheumatic Diseases has published results from the CAPRA-2 (Circadian Administration of Prednisone in Rheumatoid Arthritis-2) U.S. registration study, which demonstrated that patients with active rheumatoid arthritis (RA) treated with RAYOS® in addition to ongoing disease-modifying anti-rheumatic drug (DMARD) therapy experienced a statistically significant improvement in American College of Rheumatology (ACR) response criteria compared to placebo plus DMARD therapy. Results from this study were previously presented at the American College of Rheumatology Annual Scientific Meeting in 2010.

"For many RA patients, the most common disease symptoms including swollen and tender joints and stiffness occur in the morning," said Dr. Frank Buttgereit, principal investigator of the study, senior consultant and deputy head of the Department of Rheumatology and Clinical Immunology, Charité Hospital, Berlin, Germany. "The results from the CAPRA-2 study demonstrate that RAYOS, which is administered prior to bedtime, shows clinically and statistically significant reduction of these symptoms compared to placebo, which may provide patients relief upon awakening when their symptoms may be at their worst."

The 350-patient CAPRA-2 study was a 12-week, double blind, placebo-controlled trial evaluating RAYOS compared to placebo in patients with active RA who were receiving ongoing DMARD therapy. Eligible patients were randomized 2:1 to receive 5 mg RAYOS (N=231) or placebo (N=119) once daily, taken with or after their evening meal, in addition to their standard RA treatment. The primary endpoint of the study was ACR 20 response rate, which signifies a 20 percent improvement in tender and swollen joint counts, as well as other criteria, at week 12. A key secondary endpoint was relative reduction of the duration of morning stiffness associated with RA at week 12.

ACR 20 responses were statistically significant for patients treated with RAYOS and DMARD (48 percent) compared to patients treated with placebo and DMARD (29 percent, p < 0.001). In addition, ACR 50 response, which signifies a 50 percent improvement, was also statistically significant for patients treated with RAYOS (22 percent) compared to patients treated with placebo (10 percent, p=0.006). The greater median relative reduction in the duration of morning stiffness compared to baseline (154 minutes) was 55 percent for RAYOS patients and 35 percent for placebo patients at week 12, which was also statistically significant (p < 0.002).

Significantly greater reductions in severity of RA (Disease Activity Score 28) (p < 0.001) and fatigue (Functional Assessment of Chronic Illness Therapy - Fatigue score) (p=0.003) as well as a greater improvement in physical function (36-item Short-Form Health Survey score) (p < 0.001) were seen at week 12 for RAYOS patients compared to placebo patients.

In this study, the incidence of adverse events was slightly lower in the RAYOS group compared to the placebo group (43 percent versus 49 percent) and most events were mild or moderate in severity. The most commonly reported treatment-emergent adverse events reported with RAYOS were arthralgia (10.4 percent for RAYOS compared to 20.2 percent for placebo), RA flare (6.5 percent for RAYOS compared to 9.2 for placebo), nasopharyngitis (4.8 percent for RAYOS compared to 3.4 percent for placebo) and headache (3.9 percent for RAYOS compared to 4.2 percent for placebo).

About RA
RA is a chronic disease that causes pain, stiffness and swelling, primarily in the joints. RA affects approximately 1.8 million people in the United States and is not associated with factors such as aging.

RA occurs when the body's immune system malfunctions, attacking healthy tissue and causing inflammation, which leads to pain and swelling in the joints, and may eventually cause permanent joint damage and painful disability. The primary symptoms of RA include progressive immobility and pain, especially in the morning, with long-term sufferers experiencing continual joint destruction for the remainder of their lives.

RAYOS, known as LODOTRA® in Europe, is a proprietary delayed-release formulation of low-dose prednisone. The proprietary formulation technology of RAYOS enables a delayed-release of prednisone approximately four hours after administration. RAYOS synchronizes the prednisone delivery time with the patient's elevated cytokine levels, thereby taking effect at a physiologically optimal point to inhibit cytokine production. RAYOS utilizes SkyePharma's proprietary Geoclock™ technology.

Outside the United States, LODOTRA is approved for the treatment of moderate to severe active RA when accompanied by morning stiffness in 16 European countries and Israel and is marketed in Europe through Horizon's distribution partner Mundipharma International Corporation Limited, who also has commercial rights in certain Asian and Latin American countries. Approval in Europe was based on the CAPRA-1 study, which was a 12-week, double-blind, placebo controlled study evaluating 288 RA patients. CAPRA-1 compared the night-time administration of LODOTRA with the morning administration of immediate release prednisone at the same individual dose (average prednisone dose was 6.7 mg). Results from CAPRA-1 demonstrating a statistically significant reduction in the duration of morning stiffness associated with RA compared to patients in the immediate release group, the primary outcome of the trial (22.7 percent for LODOTRA compared to 0.4 percent for immediate release prednisone [p-value = 0.045]), were published in The Lancet 2008 (371: 205-214).

Horizon has completed the Phase 3 CAPRA-2 study for RAYOS in the United States, Europe and Canada for the treatment of the signs and symptoms of RA and in November 2011, the U.S. Food and Drug Administration accepted for filing and review Horizon's New Drug Application for RAYOS. The PDUFA action date is July 26, 2012 based on a standard 10 month review.

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

Forward-Looking Statements
This press release contains forward-looking statements, including statements regarding RAYOS, RAYOS's potential to address unmet therapeutic needs of RA patients and the status of regulatory review of RAYOS in the United States. These forward-looking statements are based on management's expectations and assumptions as of the date of this press release, and actual results may differ materially from those in these forward-looking statements as a result of various factors. These factors include, but are not limited to, the development of alternative treatments for RA, whether the FDA will approve the RAYOS NDA and the timing of its review of the NDA, the scope of the labeling for RAYOS, if approved, Horizon's ability to successfully commercialize RAYOS in the U.S., if approved, and whether healthcare professionals will prescribe RAYOS, if approved. For a further description of these and other risks facing Horizon, please see the risk factors described in Horizon's filings with the United States Securities and Exchange Commission, 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 Horizon 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
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Kathy Galante
Burns McClellan, Inc.
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