Press release from Business Wire
Apremilast Achieves Statistical Significance for the Primary and Major Secondary Endpoints in Fourth Pivotal Phase III Study (PALACE 4) of Patients with Psoriatic Arthritis
<p class='bwalignc'> <i>PALACE 4 was the first apremilast trial in DMARD-naïve patients and included more than 500 patients</i> </p> <p class='bwalignc'> <i>No new safety and tolerability signals identified, with fewer AEs and SAEs reported than in (PALACE 1, 2&3)</i> </p> <p class='bwalignc'> <i>Apremilast NDA/NDS for psoriatic arthritis submitted to health authorities in the US and Canada in Q1'2013 and Q2'2013 respectively</i> </p> <p class='bwalignc'> <i>Apremilast NDA in US for psoriasis and combined psoriatic arthritis/psoriasis MAA submission in Europe planned for 2H'2013</i> </p> <p class='bwalignc'> </p>
Monday, May 06, 2013
Apremilast Achieves Statistical Significance for the Primary and Major Secondary Endpoints in Fourth Pivotal Phase III Study (PALACE 4) of Patients with Psoriatic Arthritis14:27 EDT Monday, May 06, 2013
BOUDRY, Switzerland (Business Wire) -- Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ: CELG) today announced that statistical significance was achieved for the primary endpoint of ACR 20 at week 16 for patients receiving apremilast 20 mg and 30 mg BID monotherapy in PALACE 4. PALACE 4 is the fourth randomized, placebo-controlled study evaluating the Company's novel, oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) in patients with psoriatic arthritis. This is the first Company-sponsored trial studying patients who had not previously received an oral disease-modifying antirheumatic drug (DMARD).
“Despite recent advances in the treatment of psoriatic arthritis, there remains a significant need for more oral DMARD treatment options for DMARD-naïve patients,” said Randall Stevens, VP of Clinical Research and Development for Inflammation & Immunology. “PALACE-4 is now the fourth major randomized apremilast Phase III study to provide promising results for patients with psoriatic arthritis.”
Patients on apremilast also achieved a statistically significant benefit over placebo in key secondary endpoints, as demonstrated in various measures of physical function and signs and symptoms, including enthesitis.
No new safety and tolerability signals identified, with fewer AEs and SAEs reported than in PALACE 1, 2&3. Importantly, in PALACE 4, no systemic opportunistic infections (including TB) or lymphoma were observed through week 24, and there was no increase in risk of cardiovascular events. The most common AEs in PALACE 4 (≥5%) were nausea, diarrhea and headache.
The PALACE 4 study is ongoing and the study extension remains blinded until all patients complete week 52. Full data from this phase III study will be submitted for presentation at appropriate medical meetings.
Results from PALACE 1, one of three registrational randomized, placebo-controlled phase III studies of apremilast in PsA were released at ACR in November 2012. Top-line positive results from the two additional registrational studies of apremilast in PsA (PALACE 2 and PALACE 3) were released in September 2012. Twenty-four-week topline results of PALACE 3 and 52-week results from PALACE 1 will be presented at EULAR in June 2013. Taken together, the PALACE program is the most comprehensive set of psoriatic arthritis studies to date intended for regulatory submission. Results from the PSA-001 phase II study of apremilast in psoriatic arthritis were recently published online in the journal Arthritis & Rheumatism (http://www.onlinelibrary.wiley.com/doi/10.1002/art.34627/abstract).
In addition, positive results from two large, pivotal global studies of apremilast in more than 1,200 patients with moderate-to-severe plaque psoriasis (ESTEEM 1 and 2) were released in January 2013, with full results from ESTEEM 1 presented at AAD in March. Results from PSOR-005, a phase IIb dose-range study of apremilast in psoriasis, were recently published in The Lancet (www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60642-4/fulltext).
A randomized, placebo-controlled phase III study (POSTURE) of apremilast in ankylosing spondylitis (AS) began enrolling patients in April 2012. AS, a debilitating disease, which may cause fusion of the spine, arthritis, inflammation of the eye and damage to the heart and affects approximately 2.5 million people in the U.S. and Europe. The trial will randomize approximately 450 patients to receive 20mg or 30mg apremilast, or placebo BID. The primary endpoint is the proportion of patients achieving an ASAS 20 score at week 16.
These results are from an investigational phase III study. Apremilast is not approved for the treatment of psoriatic arthritis.
The NDA/NDS submissions, based on the combined data from PALACE 1, 2 &3 for PsA, were submitted to health authorities in the US and Canada in Q12013 and Q2 2013 respectively. The Company previously announced it expects to file a separate NDA in the US for psoriasis and a combined PsA/psoriasis MAA submission in Europe in the second half of 2013.
About PALACE 4
PALACE 4 is one of fourpivotal phase III multi-center, double-blind, placebo-controlled, parallel-group studies with 2 active-treatment groups in a DMARD-naïve patient population. More than 500 subjects were randomized 1:1:1 to receive either apremilast 20 mg BID, 30 mg BID, or identically-appearing placebo for 24 weeks, with a subsequent extension in which all patients are treated with apremilast.
The primary endpoint of the study is the proportion of patients in each treatment group who achieved the American College of Rheumatology criteria for 20% improvement (ACR20) compared to baseline at week 16. Secondary endpoints include other measures of signs and symptoms, physical function and patient-reported outcomes.
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 anti-inflammatory cytokines such as IL-10. To learn more go to www.discoverpde4.com/.
About Psoriatic Arthritis
Psoriatic arthritis is a painful, chronic inflammatory disease associated with the skin condition psoriasis. More than a million people in the U.S. and Europe are affected by this arthritic condition. Up to 30 percent of people with psoriasis eventually develop psoriatic arthritis, which involves joint inflammation and can lead to joint destruction. In addition to psoriatic skin lesions, common symptoms of psoriatic arthritis include pain, stiffness and swelling in several to many joints, as well as the spine. Patients often experience psoriasis on average for 10 years before the onset of joint symptoms, and many psoriatic arthritis patients go undiagnosed.
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.
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