Horizon Pharma, Inc. Announces Results of Phase 3 Study of Lodotra Demonstrate 12-Month Sustained Efficacy and Safety in Rheumatoid Arthritis
- Results published in July Issue of Annals of Rheumatic Diseases -
NORTHBROOK, Ill., July 23 /PRNewswire/ -- Horizon Pharma, Inc.
announced today the results from the extended open label portion of
The Circadian Administration of Prednisone in Rheumatoid
Arthritis-1 (CAPRA-1) Phase 3 European registration study of
LODOTRA®, a programmed release formulation of low-dose
prednisone, which showed sustained improvement in reducing the
duration of morning stiffness in patients with Rheumatoid Arthritis
(RA) over a 12 month period. The results were published in the July
issue of the Annals of Rheumatic Diseases and were also recently
presented at the European League Against Rheumatism (EULAR) Annual
"Symptoms of RA in patients, such as morning stiffness, show
pronounced circadian rhythms with the highest severity in the early
morning," said Frank Buttgereit, M.D., senior consultant and deputy
head of the Department of Rheumatology and Clinical Immunology,
Charite Hospital, Berlin and lead author of the study. "The results
from the open label portion of the CAPRA-1 study showed that the
efficacy of glucocorticoid therapy can be sustained by
synchronizing the drug release with the circadian rhythm of the
underlying inflammation and resulting symptoms."
The CAPRA-1 study of LODOTRA evaluated 288 patients with active
RA in a 12-week, randomized, double-blind, placebo-controlled trial
comparing bedtime administration of LODOTRA with morning
administration of immediate release (IR) prednisone at the same
individual dose (an average dose of 6.7 mg). Following the
double-blind portion of the study, 249 patients continued on to an
open label extension study for up to nine additional months, during
which all patients received only an evening dose of LODOTRA.
Variables assessed included, among other things: (i) reduction in
the duration of morning stiffness (MS) of the joints; (ii) disease
activity scores (DAS 28), a measurement of pain and swelling in 28
joints typically impacted by RA; (iii) American College of
Rheumatology (ACR) 20 response rate, which measures the percentage
of patients who have achieved a 20 percent improvement in tender
and swollen joint counts as well as a 20 percent improvement in
three of five other criteria of disease activity; and (iv) plasma
levels of interleukin-6 (IL-6), a pro-inflammatory cytokine.
Following six months of treatment in the open label portion of
the study, morning stiffness was reduced in those patients who were
in the IR prednisone group during the double-blind portion by 54
percent compared to 56 percent for patients taking LODOTRA in both
portions of the study. At 12 months, the mean relative reduction in
morning stiffness reached 55 percent in patients treated with
LODOTRA who continued treatment from the double-blind phase
compared to 45 percent in the patient group who had switched from
IR prednisone to LODOTRA.
Of patients who completed a total of 12 months in the study
(n=219), 37 percent achieved improvement in the ACR20 criteria. DAS
28 score was reduced from the mean 5.8 at baseline to 4.8 for those
taking LODOTRA and to 4.9 for the former IR prednisone group. IL-6
plasma levels were approximately 50 percent less in the
LODOTRA-treated patients compared to the IR prednisone-treated
patients after both three and 12 months of treatment.
Adverse events were observed in 51 percent of the patients
enrolled in the open label portion of the study. The most commonly
reported treatment-emergent adverse events were a flare in
RA-related symptoms (14.5 percent), upper respiratory tract
infections (2.8 percent), back pain (2.8 percent) and weight
increase (2.8 percent). Adverse events indicative of aggravated
hypothalamic-pituitary-adrenal axis suppression, typical of high
dose prednisone administration, were not observed. Adverse events
rated as being possibly related to study medication were upper
abdominal pain (1.2 percent), gastritis (1.6 percent) and weight
increase (2.4 percent). A total of 12 patients (4.8 percent)
withdrew from the study due to an adverse event.
"The results of this study suggest that low-dose
programmed-release LODOTRA may offer significant benefits over IR
prednisone for the treatment of RA, and those benefits are
maintained for up to 12 months," said Jeffrey W. Sherman, M.D.,
executive vice president, development, regulatory affairs and chief
medical officer of Horizon Pharma. "For RA patients struggling with
the debilitating impact of morning stiffness, we believe this study
provides continued evidence that a better treatment alternative is
About Rheumatoid Arthritis
RA is a chronic disease that occurs when the body's immune
system attacks the joints and other tissues of the body, causing
tissue damage including erosion and destruction of the joint
surface, as well as inflammation and joint pain. It is estimated
that between 3-4 million individuals in the U.S. and Europe are
affected by RA.
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. Morning stiffness of the joints is a hallmark of RA. Morning
stiffness, with a duration of at least one hour, has been adopted
as a diagnostic criterion for the definition of RA by the ACR.
Inflammation, soft tissue swelling, and the involvement of multiple
joints (in particular the small joints in the hands and feet) are
also common signs and symptoms that distinguish rheumatoid and
other inflammatory arthritis.
Recent research conducted by Ipsos MORI market research
involving people with RA and physicians from 11 European countries
found that nearly two thirds (60 percent) of people with RA say
that pain and stiffness in the morning controls their lives.
Additionally, nearly three quarters (74 percent) of people with
pain and stiffness in the morning as a result of their RA say that
they are either unemployed, retired early or are on sick leave as a
result of RA and more than half (58 percent) say they are
frustrated emotionally because they find it difficult to do
LODOTRA, a programmed release formulation of low-dose
prednisone, was approved in Europe in March 2009 and has been
initially launched in several European countries. LODOTRA is
currently marketed in Germany, Belgium, Denmark, Norway, and
Finland, and the company's partner Mundipharma International is
currently in the process of obtaining pricing and reimbursement
approval for LODOTRA in Austria, France, Italy, Luxembourg,
Portugal, Spain, Sweden, and the United Kingdom.
Merck Serono GmbH holds marketing rights to LODOTRA in Germany
and Austria and Mundipharma International holds marketing rights to
LODOTRA for the rest of Europe.
The company has completed a Phase 3 trial for LODOTRA in the
United States (U.S.) for the treatment of the signs and symptoms of
RA. The company anticipates submitting a New Drug Application (NDA)
for LODOTRA for the treatment of the signs and symptoms of RA to
the U.S. Food and Drug Administration (FDA) in the fourth quarter
LODOTRA is also being investigated for the treatment of severe
nocturnal asthma and polymyalgia rheumatica.
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.
Horizon has two lead product candidates, HZT-501 and LODOTRA, which
have both successfully completed multiple Phase 3 clinical trials.
Horizon submitted an NDA for HZT-501, a proprietary tablet
formulation containing a fixed-dose combination of ibuprofen and
high-dose famotidine in a single pill, to the U.S. FDA in March
2010. In two Phase 3 clinical studies (REDUCE-1 and REDUCE-2),
HZT-501 demonstrated a significant reduction in the incidence of
upper gastrointestinal ulcers in patients with chronic pain or
arthritis when treated with HZT-501 versus ibuprofen alone.
LODOTRA, a programmed release formulation of low-dose prednisone,
received regulatory approval in Europe in March 2009 for the
reduction of morning stiffness associated with RA.
For more information about the company and its products, please
Forward Looking Statements
This press release includes forward-looking statements that are
subject to risks, uncertainties and other factors. All statements
other than statements of historical fact are statements that could
be deemed forward-looking statements, including, but not limited
to, any statements regarding the potential development and
commercialization of LODOTRA and HZT-501 and the efficacy and
commercial and therapeutic potential of these product candidates,
including the potential for LODOTRA for the treatment of signs and
symptoms of RA and the anticipated timing of the submission of an
NDA for LODOTRA and the potential for HZT-501 to reduce the
incidence of upper gastrointestinal ulcers and the timing of
approval of its NDA; and any statements of the plans, strategies
and objectives of management for future operations of the company.
Such statements are only predictions, and actual events or results
may differ materially from those projected in such forward-looking
statements. Factors that could cause or contribute to the
differences include, but are not limited to, the FDA may not agree
with the company's interpretation of efficacy and safety results;
LODOTRA and HZT-501 may not receive regulatory approval on a timely
basis or at all; the overall inherent risks of product development
and approval, clinical outcomes, regulatory risks, risks related to
proprietary rights, risks relating to obtaining price and cost
reimbursement for marketed drugs, market acceptance and competition
and risks associated with the company's ability to obtain
additional capital to support its planned operations.
Source: Horizon Pharma, Inc.
CONTACT: Robert J. De Vaere, Executive Vice President and
Financial Officer, +1-760-436-4010, firstname.lastname@example.org; or Susan
Web Site: http://www.horizonpharma.com/
Posted: July 2010