PLEASE SCROLL DOWN TO THE RESULTS SECTION (below) TO SEE THE OUTCOME OF THIS EVENT.
Robert J. Hugin, President and CEO, maintained guidance for the enrollment completion of the Apremilast phase III programs. He stated, "Our immunology and inflammation franchise is making significant progress with full enrollment of the 6 phase III Apremilast studies expected by year end."
Source: Q2 2011, earnings conference call, 7/28/11.
Robert J. Hugin, President and CEO, gave an update on the progress being made with enrollment in the Apremilast programs. He stated, "We are making excellent progress with our Apremilast program, 6 phase III trials are studying the efficacy and safety of Apremilast in psoriasis and psoriatic arthritis and are accruing ahead of schedule. We also expect phase II data in at least one additional indication to be available later this year."
Source: Q1 2011, earnings conference call, 4/28/11.
Robert J. Hugin, President and CEO, gave guidance for data from the Apremilast for psoriasis programs. He stated, "During the last two quarters, we have initiated four out of our six pivotal studies in psoriasis and psoriatic arthritis with Apremilast. Our phase III program encompasses approximately 3,500 patients at 450 sites worldwide. Our ambitious but obtainable corporate objective is to have all patients in our pivotal studies enroll by the end of 2011, with data available as early as mid 2012."
Source: Q3 2010, earnings conference call, 10/28/10.
Robert J. Hugin, President and CEO, gave an overview of the time-line for the Apremilast phase III development programs. He stated, "Our most advanced program is Apremilast. In just the past few weeks, we have dosed our first patients in PSA-002, the first of our pivotal trials. We have an extensive development program for Apremilast in psoriatic arthritis, moderate-to-severe psoriasis, rheumatoid arthritis and other serious immune/inflammatory diseases. All of our pivotal trials in psoriatic arthritis and psoriasis are targeted to be initiated before the end of this year."
Source: Q2 2010 earnings conference call, 7/29/10.
PALACE-1 - A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy and Safety Study of Two Doses Of Apremilast (CC-10004) In Subjects With Active Psoriatic Arthritis
Estimated Enrollment: 495
Study Start Date: June 2010
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Source: clinical trials.gov. http://clinicaltrials.gov/ct2/show/NCT01172938?term=apremilast&phase=2&r...
|Apremilast (CC-10004) Psoriatic arthritis||Rheumatology||Psoriatic arthritis||Anti-inflammatory||Immune system|
Mechanism of action: CC-10004 (apremilast), a SM-inhibitor, down regulates inflammatory reactions via an orally available small molecules that inhibit the production of multiple pro inflammatory mediators including: interleukin-2 (IL-2), IL-12, interferon-gamma, TNF-alpha, leukotrienes, and nitric oxide synthase.
Phase of Development: III
Event Type: Data: Phase III trial results
Dates: 2012-03-01 - 2012-05-31
Oral OTEZLA(R) (Apremilast) Showed Sustained Clinical Response over Two Years in Patients with Active Psoriatic Arthritis
ACR 20 response rates sustained with continued OTEZLA treatment through 104 weeks - 65.3 percent and 61.4 percent in PALACE 1 and 4, respectively
Eighty four percent of patients who completed one year of treatment with OTEZLA continued on OTEZLA through week 104 in both trials
The rates of most commonly reported adverse events of diarrhea, nausea and headache decreased during the 52 to 104 week period compared to the 0 to 52 week period
SUMMIT, N.J. --(BUSINESS WIRE)-- Celgene Corporation (NASDAQ:CELG), today announced that results from long-term (104-week) efficacy and safety analyses of OTEZLA® (apremilast) from the open-label phase of two PALACE phase III clinical trials were presented at the 2014 American College of Rheumatology (ACR)/ Association of Rheumatology Health Professionals (ARHP) annual meeting in Boston . OTEZLA is the Company's oral, selective inhibitor of phosphodiesterase 4 (PDE4), approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with active psoriatic arthritis and for the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
In PALACE 1, 84 percent (144/171) of patients who completed one year (52 weeks) of 30 mg twice daily therapy continued to receive OTEZLA at two years (104 weeks). Improvements in efficacy measures observed at 52 weeks were sustained through 104 weeks of treatment. At week 104, among patients receiving OTEZLA 30 mg twice daily, the ACR20 response rate was 65.3 percent. ACR50 and 70 response rates were 34.0 percent and 19.6 percent, respectively, at week 104.
Similar findings were observed in PALACE 4. In this trial, nearly 84 percent (168/201) of DMARD-naïve patients who completed one year of OTEZLA 30 mg twice daily monotherapy continued to receive OTEZLA at two years. At week 104, among patients treated with OTEZLA 30 mg twice daily monotherapy, an ACR20, 50 and 70 response was reached by 61.4 percent, 40.7 percent and 19.2 percent of patients, respectively.
In both PALACE 1 and PALACE 4, changes in other efficacy measures—including the HAQ-DI, which assesses improvements in physical function, and swollen and tender joint counts—were also generally sustained between weeks 52 and 104 with continued OTEZLA treatment. In PALACE 4, treatment with OTEZLA in patients with pre-existing enthesitis (inflammation at sites where tendons or ligaments insert into bone) or dactylitis (inflammation of an entire digit), two key manifestations of psoriatic arthritis, resulted in improvements in enthesitis and dactylitis that were sustained through 104 weeks of treatment.
"Given the chronic nature of this condition, dealing with psoriatic arthritis can be an ongoing struggle for many people," said Alvin Wells , M.D., Ph.D., director, Rheumatology and Immunology Center, Franklin, WI. "Evidence-based data show that different treatment options are frequently required to continue to manage a patient's symptoms. At our center, we see patients with active psoriatic arthritis who present with significant disease activity despite effective prior treatments. These new data from ongoing open-label studies add to our understanding of how apremilast may help meet treatment goals in such patients."
Similar to adverse events (AEs) reported during weeks 0 to 52 in PALACE 1 and 4, most AEs reported during weeks 52 to 104 were mild or moderate in severity. The rates of diarrhea, nausea, headache and upper respiratory tract infection (URTI)—AEs reported in at least five percent of patients receiving OTEZLA 30 mg twice daily at 52 weeks in both studies—decreased or were similar between weeks 52 to 104 compared with the 0 to 52 week period. Rates of diarrhea, nausea, headache and URTI at week 104 in PALACE 1 and 4 respectively, were as follows: diarrhea (1.8 percent and 2.0 percent), nausea (0.6 percent and 2.0 percent), headache (4.7 percent and 1.0 percent) and URTI (4.7 percent and 4.5 percent). Serious AEs occurred in 4.7 percent and 5.0 percent of patients, respectively. In addition, discontinuation rates due to AEs in both studies decreased during the 52 to 104 week period compared with the 0 to 52 week period.
Oral Apremilast Demonstrated Long-Term Clinical Benefits for Patients with Psoriatic Arthritis
Up to 63 percent of patients achieved ACR 20 at week 52, generally consistent with PALACE 1
Clinically meaningful improvements demonstrated in all key manifestations of psoriatic arthritis at week 52
Apremilast demonstrated a consistent safety profile across three long-term PALACE phase III studies of 1493 patients over 52 weeks
Tolerability improved in pooled analysis between weeks 24 and 52
No clinically meaningful changes in laboratory measurements were demonstrated in the pooled analyses
BOUDRY, Switzerland--(BUSINESS WIRE)--Oct. 28, 2013-- Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation (NASDAQ: CELG), today announced results of three long-term (52-week) phase III studies of apremilast, the Company’s first-in-class, oral, targeted inhibitor of phosphodiesterase 4 (PDE4), in psoriatic arthritis at the 2013 American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) annual meeting in San Diego. The studies included 52-week efficacy results from PALACE 2 and 3 and 52-week pooled safety data analyses from PALACE 1, 2 and 3, including effects on laboratory measurements.
“Psoriatic arthritis is a debilitating chronic disease requiring long-term treatment,” stated Maurizio Cutolo, M.D., Research Laboratories and Clinical Academic Division of Rheumatology at the University Medical School of Genova, Italy. “The one-year data from the PALACE trials suggest that, with continued treatment, early responses to apremilast are durable over time. Based on the efficacy and safety data to date from phase III studies, apremilast has the potential to offer an additional treatment option for the long-term management of psoriatic arthritis.”
PALACE 2 and PALACE 3: 52-week efficacy data
Three pivotal studies (PALACE 1, 2 and 3) were conducted in patients with active psoriatic arthritis who had prior experience with conventional DMARDs and/or biologics. The long-term (52 weeks) results from PALACE 1 have been previously reported. Today, the long-term results from the two additional pivotal phase III studies (PALACE 2 and PALACE 3) were reported. Consistent with the results from PALACE 1, significantly more patients receiving apremilast 20 mg or 30 mg twice daily (BID) achieved a modified American College of Rheumatology (ACR) 20 response at week 16 (primary endpoint) than did patients taking placebo in both PALACE 2 (placebo, 20%; apremilast 20 mg BID, 38%, P=0.0002; apremilast 30 mg BID, 34%, P=0.0024) and PALACE 3 (placebo, 19%; apremilast 20 mg BID, 29%, P<0.05; apremilast 30 mg BID, 43%, P<0.0001). Clinically meaningful improvements were also demonstrated in signs and symptoms, physical function and other manifestations chartacteristic of psoriatic arthritis, including swollen and tender joints, skin and quality of life.
Sustained improvements in the percentage of patients achieving a modified ACR 20 response at week 52 were observed in both PALACE 2 (apremilast 20 mg BID, 52.9%; apremilast 30 mg BID, 52.6%) and PALACE 3 (apremilast 20 mg BID, 56.0%; apremilast 30 mg BID, 63.0%) for those patients randomized to apremilast and completing 52 weeks of treatment.
PALACE 1, PALACE 2 and PALACE 3: pooled 52-week safety data
Long-term (52 weeks) safety results from a pooled analysis of the PALACE 1, 2 and 3 trials (including 1,493 patients) identified no new safety findings for patients with psoriatic arthritis who were treated with apremilast for up to 52 weeks, compared with the previously reported 24 week safety results. Previously reported adverse events (AEs) were less frequent in weeks 24 to 52 than in weeks 0 to 24.
Most AEs were mild or moderate in severity and did not lead to discontinuation. The most commonly reported AEs were nausea, diarrhea, headache, upper respiratory tract infection and nasopharyngitis. Nausea and diarrhea were predominantly mild in severity, occurred most frequently in the first two weeks of treatment, and often resolved within a month despite continued treatment. Serious AEs occurred at low rates, were comparable across treatment groups and did not increase with long-term apremilast exposure, based on exposure-adjusted incidence rates per 100 subject years.
Exposure-adjusted incidence rates per 100 subject years of major adverse cardiac events, serious infections, including opportunistic infections, and malignancies were comparable with those of placebo. No cases of tuberculosis (new or reactivations) were reported with either dose of apremilast.
PALACE 1, PALACE 2 and PALACE 3: laboratory monitoring
The effect of apremilast on laboratory measurements was also assessed in a pooled analysis of 1,493 patients (placebo, 495; apremilast 20 mg BID, 501; apremilast 30 mg BID, 497) with psoriatic arthritis from the PALACE 1, 2 and 3 trials. No clinically meaningful changes in laboratory measurements were noted, suggesting that ongoing laboratory monitoring may not be necessary.
These results are from investigational studies. Apremilast is not an approved product for any indication.
The New Drug Application (NDA) and the New Drug Submission (NDS), based on the combined data from PALACE 1, 2 and 3 for psoriatic arthritis, were submitted to health authorities in the U.S. and Canada in Q1 2013 and Q2 2013, respectively. An NDA to the U.S. Food and Drug Administration for psoriasis, in addition to a combined psoriatic arthritis/psoriasis Marketing Authorization Application (MAA) in Europe, are on-track for the fourth quarter of 2013.
Source: press release, 10/28/13. http://ir.celgene.com/phoenix.zhtml?c=111960&p=irol-newsArticle&ID=18689...
Signs and Symptoms of Psoriatic Arthritis Significantly Improved in Patients Receiving Long-Term Oral Apremilast Treatment in Phase III Study (PALACE-1)
52-week data revealed improving efficacy over time, reporting ACR 20 scores to 63% and 55% for the two apremilast dose groups; similar improvements reported in ACR 50 and ACR 70 scores
PALACE 1 apremilast data selected for inclusion at EULAR press conference
BOUDRY, Switzerland--(BUSINESS WIRE)--Jun. 12, 2013-- ABSTRACT #LB0001
Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation (NASDAQ: CELG), today announced 52-week results from PALACE 1, the Company’s first phase III study in psoriatic arthritis at the European Congress of Rheumatology (EULAR) annual meeting in Madrid, Spain. The results were included in the EULAR press conference, which highlights data considered representative of highest quality and most meaningful research presented at EULAR. The full PALACE 1 oral presentation will be presented later today. (https://b-com.mci-group.com/AbstractList/EULAR2013.aspx).
Long-term results presented from PALACE 1 revealed meaningful improvements in American College of Rheumatology (ACR) 20 scores from week 24 through week 52. Patients who received apremilast for 52 weeks demonstrated ACR scores of 63% for apremilast 20 mg BID and 55% for apremilast 30 mg BID. Similar improvements over time were observed in the ACR 50 and ACR 70 scores.
“I am excited that results from the first long-term PALACE data were selected for inclusion at the EULAR press conference,” stated Dr. Arthur Kavanaugh, Professor of Clinical Medicine and Director of the Center for Innovative Therapy at the University of California, San Diego School of Medicine. “There is a high unmet medical need for additional efficacious, well-tolerated treatment options for patients with psoriatic arthritis.”
PALACE 1 is the first completed pivotal phase III, randomized, placebo-controlled study evaluating the Company’s oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) in patients with psoriatic arthritis who had received oral disease-modifying antirheumatic drugs (DMARD) and/or biologic therapy and/or had failed on an anti-tumor necrosis factor (TNF) agent. Apremilast treatment in this study was used alone or in combination with oral DMARDs. PALACE 2 and PALACE 3 have completed the primary end-point phases and are in long-term follow-up.
The safety and tolerability profile of apremilast during the 52-week period was consistent with what was observed in the placebo-controlled portion of the trial (0-24 weeks) and with what was observed in other PALACE trials to date. Importantly, there were no safety signals with respect to major cardiac events, malignancies, including lymphoma or systemic opportunistic infections, and no cases of reactivations of tuberculosis were reported for the 52-week period. At week 52, the most common treatment-emergent adverse events (TEAEs) reported (>5%) included nausea, diarrhea, headache, URTI and nasopharyngitis.
These results are from investigational studies. Apremilast is not an approved product for any indication.
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 Q1 2013 and Q2 2013, respectively. The Company previously announced it expects to file a separate NDA/NDS in the US/Canada for psoriasis and a combined PsA/psoriasis MAA submission in Europe in the second half of 2013.
Source: press release, 6/12/13. http://ir.celgene.com/phoenix.zhtml?c=111960&p=irol-newsArticle&ID=18291...
Oral Apremilast Achieves Statistical Significance for the Primary Endpoint of ACR20 in the First Phase III Study (PALACE-1) in Patients with Psoriatic Arthritis
Apremilast significantly improves signs and symptoms of PsA in DMARDs-failure patients, including biologic-treatment-failure patients
Apremilast monotherapy demonstrates robust improvement across primary and secondary endpoints
Highest response demonstrated in biologic-naïve patient population
No significant safety signals were observed and tolerability improved over phase II program
BOUDRY, Switzerland--(BUSINESS WIRE)--Nov. 13, 2012-- Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ: CELG) today presented the results from PALACE-1, the Company’s first Phase III study in psoriatic arthritis, at the American College of Rheumatology annual meeting in Washington, D.C.
The company previously announced statistical significance for the primary endpoint of ACR20 for patients receiving apremilast in the PALACE-1 study, the first of three pivotal phase III, randomized, placebo-controlled studies evaluating the Company’s novel, oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) in patients with psoriatic arthritis who had received oral disease-modifying antirheumatic drugs (DMARD) and/or biologic therapy and/or had failed on an anti-tumor necrosis factor (TNF) agent. Apremilast treatment in this study was used alone or in combination with oral DMARDs. PALACE-1 is the first phase III study demonstrating statistical significance in a psoriatic arthritis patient population that included both prior biologic exposure (23.6%) and biologic failures (9.3%).
Source: press release, 11/13/12. http://ir.celgene.com/phoenix.zhtml?c=111960&p=irol-newsArticle&ID=17582...
Apremilast Achieves Statistical Significance for the Primary Endpoint of the First Phase III Study (PALACE-1) in Patients with Psoriatic Arthritis
Apremilast achieves clinically meaningful and statistically significant improvement in measures of both signs and symptoms and physical function
Safety is consistent with previous studies and tolerability improved over phase II program
Celgene targets first apremilast NDA filing in the first half of 2013
Update on comprehensive global apremilast clinical program
BOUDRY, Switzerland--(BUSINESS WIRE)--Jul. 12, 2012-- Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ: CELG) today announced top-line results from the PALACE-1 study, the first of three pivotal phase III, randomized, placebo-controlled studies evaluating the Company’s novel, oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) in patients with psoriatic arthritis who had received an oral disease-modifying antirheumatic drug (DMARD), biologic therapy or had failed on an anti-tumor necrosis factor (TNF) agent. Apremilast treatment in this study was used alone or in combination with an oral DMARD.
Source: press release, 7/12/12. http://ir.celgene.com/phoenix.zhtml?c=111960&p=irol-newsArticle&ID=17141...