Horizon Pharma Presents New Clinical Data Demonstrating RAYOS(R) (Prednisone)
Delayed-Release Tablets Produce a Sustained Reduction in
Morning Symptoms in Patients With Rheumatoid Arthritis
Data Presented During ACR/ARHP Annual Scientific Meeting
DEERFIELD, IL -- (Marketwired) -- 10/29/13 -- Horizon Pharma, Inc.
(NASDAQ: HZNP) today announced new analyses of data reported for the
first time from the Circadian Administration of Prednisone in
Rheumatoid Arthritis-1 (CAPRA-1) clinical trial. The data
demonstrated that patients with rheumatoid arthritis (RA) treated
with Horizon's approved RAYOS(R) (prednisone) delayed-release (DR)
tablets, given at bedtime, had significant and sustained improvement
in morning symptoms for the one-year duration of the study as
compared to a group of patients treated with immediate release (IR)
prednisone, given in the waking hours. The data also showed that
patients previously treated for three months with IR prednisone who
were switched to RAYOS experienced significant improvement in morning
symptoms and an associated inflammatory marker for the nine-month
treatment period. The data were presented during the American College
of Rheumatology (ACR)/Association of Rheumatology Health
Professionals (ARHP) Annual Scientific Meeting, taking place in San
Diego, CA, October 25-30, 2013.
"It is well known that morning symptoms of rheumatoid arthritis,
including joint stiffness and pain, are extremely common and are
associated with inflammatory circadian rhythms and the night time
rise of cytokines in the body. These new analyses further indicate
that the timing of prednisone administration is important to improve
morning symptoms and associated inflammation in patients with
rheumatoid arthritis," commented Allan Gibofsky, M.D., senior author
of one of the two abstracts presented at the ACR meeting, and
Professor of Medicine and Public Health at Weill Cornell Medical
College and Attending Rheumatologist at the Hospital for Special
Surgery in New York City.
The CAPRA-1 trial was conducted in two phases. The first phase was a
double-blind, three-month active comparator controlled study that
randomized RA patients on a stable low dose of prednisone therapy to
either RAYOS (N=144) taken once daily at bedtime (approximately 10
p.m.) or to continue on IR prednisone (N=144), taken in the morning.
Both groups received the equivalent prednisone dose previously
administered. Visits included baseline, weeks 2, 6 and 12. The second
phase was open-label treatment, which allowed those patients
previously randomized to IR prednisone who completed the first phase
of the study (N=129) to switch to RAYOS. Those patients previously
randomized to RAYOS who completed the first phase of the study
(N=120) were permitted to continue on RAYOS. Visits included baseline
(switch at end of double-blind phase), 3, 6, and 9 months.
Inflammatory cytokine interleukin (IL)-6 samples were obtained at
baseline and 9 months. The primary outcomes for these analyses were
absolute and relative reduction in morning stiffness, threshold
responses of at least 25%, 50%, and 75% improvement in morning
stiffness duration from baseline, change in mean absolute pain
measured in a visual analog scale (VAS), change in mean absolute
patient global assessment VAS, and IL-6 levels. For both analyses,
patients who entered the open-label phase were required to have at
least one diary entry. All diary entries +/- 4 weeks of each of the 3
month visits were utilized. No additional safety signals were
identified in analyses conducted for either abstract presentation.
-- According to the presentation titled, Threshold Analysis of Patient
Reported Morning Stiffness Where Delayed-Release (DR) Prednisone Was
Compared to, and Replaced, Immediate Release Prednisone in Rheumatoid
Arthritis (RA) Patients Receiving Conventional Disease-Modifying
Antirheumatic Drugs (DMARDs) Over 1 Year, the RAYOS study arm had
statistically significantly more responders in each of the 3 response
categories (25/50/75%) of morning stiffness at the end of the
double-blind period as compared to IR prednisone (p ≤ 0.05), and
the separation of responses began after the first week of therapy.
Patients who were randomized to IR prednisone in the blinded phase,
when switched to RAYOS in the open-label phase, had comparable
responses in all categories within three months and significantly
shorter time to response when compared to patients already receiving
RAYOS (p ≤ 0.008). The data abstract is available at:
-- In the presentation titled, Switching From Immediate Release (IR)
Prednisone to Delayed Release (DR) Prednisone Improves Patient
Reported Outcomes In Rheumatoid Arthritis (RA) Patients On
Conventional Disease-Modifying Antirheumatic Drugs (DMARDs), the
absolute reduction of morning stiffness duration was approximately 50
minutes from baseline (end double-blind phase) for patients switching
from IR prednisone to RAYOS at the initiation of the open-label phase.
The relative reduction in morning stiffness duration was observed at
the first visit after switching treatment regimens and was maintained
over the nine months of open-label treatment. A significant
improvement in pain VAS (mean absolute change -6.1, p = 0.002) three
months after the switch from IR prednisone to RAYOS was observed and
then a stabilization with a non-significant reduction at month 9. A
significant improvement in patients' global assessment VAS (mean
absolute change -7.9, p
RAYOS, known as LODOTRA(R) in Europe, is a proprietary
delayed-release formulation of low-dose prednisone. The
pharmacokinetic profile of RAYOS is different with an approximately
four-hour lag time from that of IR prednisone formulations. In
clinical trials studying use of RAYOS in RA, patients were
administered RAYOS at 10 p.m. with food. The delayed-release profile
of RAYOS helps to achieve therapeutic prednisone blood levels at a
time point when inflammatory cytokine levels start rising during the
middle of the night. While the pharmacokinetic profile of RAYOS
differs in terms of lag time from IR prednisone, its absorption,
distribution and elimination processes are comparable. For more
information, please visit www.RAYOSrx.com.
RAYOS utilizes SkyePharma's proprietary Geoclock(TM) technology.
Outside the United States, LODOTRA is approved for the treatment of
moderate to severe active RA when accompanied by morning stiffness in
over 30 countries. Horizon has granted commercialization rights for
LODOTRA in Europe, Asia and Latin America to its distribution partner
Mundipharma International Corporation Limited. Horizon has an
exclusive license from SkyePharma for RAYOS.
Important Safety Information
RAYOS(R) (prednisone) delayed-release tablets
Approved uses of RAYOS
RAYOS, a delayed-release form of prednisone,
prevents the release of substances in the body that cause
inflammation. RAYOS is approved to treat a broad range of diseases
including rheumatoid arthritis (RA), polymyalgia rheumatica (PMR),
psoriatic arthritis (PsA), ankylosing spondylitis (AS), asthma and
chronic obstructive pulmonary disease (COPD). For a full list of
RAYOS indications, please see full prescribing information at
RAYOS is contraindicated in patients who have known hypersensitivity
to prednisone or to any of the excipients. Rare instances of
anaphylaxis have occurred in patients receiving corticosteroids.
Important information about RAYOS
Do not use RAYOS if you are
allergic to prednisone.
Long-term use of RAYOS can affect how your body responds to stress.
Symptoms can include weight gain, severe fatigue, weak muscles and
high blood sugar.
RAYOS can weaken your immune system, making it easier for you to get
an infection or worsening an infection you already have or have
RAYOS can cause high blood pressure, salt and water retention and low
There is an increased risk of developing holes in the stomach or
intestines if you have certain stomach and intestinal disorders.
Behavior and mood changes can occur, including intense excitement or
happiness, sleeplessness, mood swings, personality changes or severe
Long-term use of RAYOS can cause decreases in bone density.
RAYOS can cause cataracts, eye infections and glaucoma.
Do not receive a "live" vaccine while taking RAYOS. The vaccine may
not work as well during this time and may not fully protect you from
Taking RAYOS during the first trimester of pregnancy can harm an
Long-term use of RAYOS can slow growth and development in children.
The most common side effects with RAYOS are water retention, high
blood sugar, high blood pressure, unusual behavior and mood changes,
increased appetite and weight gain.
Please see full prescribing information for RAYOS at www.RAYOSrx.com.
About Horizon Pharma
Horizon Pharma, Inc. is a specialty
pharmaceutical company that has developed and is commercializing
DUEXIS(R) and RAYOS/LODOTRA, both of which target unmet therapeutic
needs in arthritis, pain and inflammatory diseases. The Company's
strategy is to develop, acquire, in-license and/or co-promote
additional innovative medicines where it can execute a targeted
commercial approach in specific therapeutic areas while taking
advantage of its commercial strengths and the infrastructure the
Company has put in place. For more information, please visit
This press release contains
forward-looking statements, including statements regarding the
potential for RAYOS to produce a sustained reduction in morning
symptoms in patients with RA and to improve outcomes in RA patients
switching from IR prednisone and the importance of timing of
prednisone administration in improving morning symptoms and
associated inflammation in patients with RA. 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, including, but not limited to, how physicians
prescribe and patients use RAYOS, and competition in the market for
RAYOS. 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
Burns McClellan, Inc.
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