Apremilast Esteem Program Meets Primary and Major Secondary Endpoint in Pivotal Phase Iii Psoriasis Trials
Clinical Data from two pivotal phase III (ESTEEM 1&2) randomized, placebo-controlled studies including approximately 1,250 patients demonstrated statistically significant and clinically meaningful improvements for the primary and major secondary endpoint
NDA submission based on ESTEEM program in psoriasis planned for H2’2013; MAA submission for psoriasis and psoriatic arthritis planned for H2’2013
No new safety signals were observed and tolerability improved over phase II psoriasis trial results; Safety and tolerability consistent with phase III psoriatic arthritis trials
Data from the phase III ESTEEM program is planned for
presentation
at upcoming major medical meetings
BOUDRY, Switzerland – (Jan. 7, 2013) – Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ: CELG), today announced that statistical significance for the primary endpoint of PASI 75 at week 16 was achieved for patients receiving apremilast 30 mg BID monotherapy in both the ESTEEM 1 & 2 phase III studies. ESTEEM 1 & 2 are the two pivotal phase III, randomized, placebo-controlled studies evaluating apremilast, the company’s oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) in patients with moderate to severe chronic plaque psoriasis.
Patients on apremilast also achieved a statistically significant benefit over placebo in the major secondary endpoint, Static Physician Global Assessment (sPGA).
“Psoriasis is a common immune-mediated skin disease affecting nearly 125 million people worldwide,” said Kim Papp, M.D., Ph.D. of Probity Medical Research, Canada. “Despite advances in treatment over the last decade, a significant proportion of moderate to severe psoriasis patients remain inadequately treated. The primary reason for psoriasis patients not receiving adequate therapy is the burden associated with available treatment options. As a consequence, there is a high unmet medical need for an efficacious, safe, oral option that patients can take long-term.”
An NDA submission for psoriasis, based on ESTEEM 1 & 2 data, is expected in the second half of 2013. The company previously announced it expects to file an NDA for psoriatic arthritis (PsA) in the first quarter of 2013 and a combined MAA for psoriasis and psoriatic arthritis in Europe in the second half of the year.
The Phase III safety and tolerability data are improved over previously observed phase II psoriasis data and consistent with results from the phase III psoriatic arthritis trials. The overall psoriasis safety database includes nearly 2,000 patients to date. ESTEEM 1 & 2 are ongoing trials. Subjects are being evaluated for safety and efficacy in the long-term extension studies for up to an additional four years. Approximately one-third of the study population was treatment-naïve and two-thirds had prior exposure to either systemic and/or phototherapy; approximately one-third of the overall study population had prior biologic therapy.
To date, the five positive phase III studies from the ESTEEM and PALACE programs represent the most comprehensive clinical data for submission for patients with psoriatic disease. Clinical data from ESTEEM 1 & 2 are planned for presentation at upcoming major medical meetings.
About ESTEEM 1 & 2
ESTEEM 1 & 2 are two pivotal phase III randomized,
placebo-controlled study evaluating apremilast in subjects with a
diagnosis of moderate to severe chronic plaque psoriasis for at
least 12 months prior to the screening, and at baseline, and who
are also a candidate for phototherapy and/or systemic therapy.
Approximately 1,250 patients were randomized 2:1 to receive either
apremilast 30 mg BID or placebo for the first 16 weeks, followed by
a maintenance phase from weeks 16-32 in which placebo subjects were
switched to apremilast 30 mg BID through week 32, and a randomized
withdrawal phase for responders from Week 32-Week 52 based on their
initial randomization and PASI response.
About Apremilast
Apremilast, an oral small-molecule inhibitor of phosphodiesterase 4
(PDE4), works intracellularly to modulate a network of
pro-inflammatory and anti-inflammatory mediators. PDE4 is a cyclic
adenosine monophosphate (cAMP)-specific PDE and the dominant PDE in
inflammatory cells. PDE4 inhibition elevates intracellular cAMP
levels, which in turn down-regulates the inflammatory response by
modulating the expression of TNF-α, IL-23, and other
inflammatory cytokines. Elevation of cAMP also increases other
anti-inflammatory cytokines such as IL-10.
About Psoriasis
Psoriasis is an immune-mediated, non-contagious chronic
inflammatory skin disorder of unknown cause. The disorder is a
chronic recurring condition which varies in severity from minor
localized patches to complete body coverage. Plaque psoriasis is
the most common type of psoriasis. About 80 percent of people who
develop psoriasis have plaque psoriasis, which appears as patches
of raised, reddish skin covered by silvery-white scales. These
patches, or plaques, frequently form on the elbows, knees, lower
back, and scalp. Psoriasis occurs nearly equally in males and
females. Recent studies show that there may be an ethnic link.
Psoriasis is believed to be most common in Caucasians and slightly
less common in other ethnic groups. Worldwide, psoriasis is most
common in Scandinavia and other parts of northern Europe. About 10
percent to 30 percent of patients with psoriasis also develop a
condition called psoriatic arthritis, which causes pain, stiffness
and swelling in and around the joints.
About Celgene International Sàrl
Celgene International Sàrl, located in Boudry, in the Canton
of Neuchâtel, Switzerland, is a wholly owned subsidiary and
international headquarters of Celgene Corporation. Celgene
Corporation, headquartered in Summit, New Jersey, is an integrated
global pharmaceutical company engaged primarily in the discovery,
development and commercialization of innovative therapies for the
treatment of cancer and inflammatory diseases through gene and
protein regulation. For more information, please visit the
Company's website at www.celgene.com.
Forward-Looking Statements
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are generally statements that are not historical facts.
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Forward-looking statements are based on management’s current
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forward-looking statement in light of new information or future
events, except as otherwise required by law. Forward-looking
statements involve inherent risks and uncertainties, most of which
are difficult to predict and are generally beyond our control.
Actual results or outcomes may differ materially from those implied
by the forward-looking statements as a result of the impact of a
number of factors, many of which are discussed in more detail in
our Annual Report on Form 10-K and our other reports filed with the
Securities and Exchange Commission.
Posted: January 2013
