Psoriasis is an immune mediated skin condition characterised by raised
scaly lesions on the skin. It affects approximately 14 million people
"This CHMP positive opinion is an important step forward for people with
psoriasis and psoriatic arthritis in
In the ESTEEM studies, which form the basis of CHMP's positive opinion
for apremilast in psoriasis, treatment resulted in significant and
clinically meaningful improvements in plaque psoriasis as measured by
In the PALACE program, which forms the basis for CHMP's positive opinion
for apremilast in psoriatic arthritis, treatment resulted in significant
and clinically meaningful improvements in the signs and symptoms of
psoriatic arthritis, as measured by the modified ACR-20 (a 20 percent
improvement in the
In the two Phase III programs, PALACE and ESTEEM, the clinical response of OTEZLA was maintained through week 52 across multiple endpoints. 15,16
Across these phase III clinical studies, the most commonly reported adverse reactions were consistently diarrhoea, nausea, upper respiratory tract infection, tension headache and headache.6,11 These adverse reactions were mostly mild to moderate in severity. Gastrointestinal adverse reactions generally occurred within the first two weeks of treatment and usually resolved within four weeks.6,11 During the placebo-controlled phase of the clinical trials, the rate of major adverse cardiac events, serious infections, including opportunistic infections, and malignancies, was comparable between placebo and apremilast groups.6,11
OTEZLA® was approved on
Note to editors: Additional information can be found at: http://smp.businesswire.com/pages/celgene-receives-positive-chmp-opinion-otezla-apremilast-first-oral-pde4-inhibitor-treatment
OTEZLA® is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic AMP (cAMP). PDE4 inhibition results in increased intracellular cAMP levels which is thought to indirectly modulate the production of inflammatory mediators. The specific mechanism(s) by which OTEZLA® exerts its therapeutic action in patients with psoriasis or psoriatic arthritis is not well defined.17 Find out more about PDE4 inhibition, by clicking here: http://discoverpde4.com/
About ESTEEM 1 and 2
ESTEEM 1 and 2 are two large pivotal phase III randomized, placebo-controlled studies evaluating apremilast in patients with a diagnosis of moderate to severe plaque psoriasis for at least 12 months prior to screening, and who were also candidates for phototherapy or systemic therapy. Approximately 1,250 patients were randomized 2:1 to receive either apremilast 30 mg twice daily or placebo after an initial five-day titration period, for the first 16 weeks, followed by a maintenance phase from weeks 16-32 in which placebo patients were switched to apremilast 30 mg twice daily through week 32, and a randomized withdrawal phase for responders from week 32 to week 52 based on their initial apremilast randomization and Psoriasis Area and Severity Index (PASI) response. Approximately 30 percent of all patients had received prior phototherapy and 54 percent had received prior conventional systemic and/or biologic therapy.
About PALACE Program
PALACE 1, 2 and 3 are three pivotal phase III multi-center, double-blind, placebo-controlled, parallel-group studies with two active-treatment groups. Across these studies, approximately 1,500 patients were randomized 1:1:1 to receive either apremilast 20 mg twice daily, apremilast 30 mg twice daily or identically-appearing placebo, for 16 weeks. At week 16, some placebo-treated patients were randomized to one of the two apremilast groups, while others remained on placebo through week 24. After week 24, patients began a subsequent long term, open-label, active treatment phase. The PALACE 1, 2 and 3 studies included a wide spectrum of patients with active psoriatic arthritis, who had been previously treated with oral disease-modifying anti rheumatic drugs (DMARDs), and/or biologics, with some patients who had previously failed a tumour necrosis factor (TNF) blocker. Taken together, the PALACE program is the largest psoriatic arthritis program to date intended for regulatory submission.
ADDITIONAL IMPORTANT SAFETY INFORMATION based on US label
Otezla® (apremilast) is contraindicated in patients with a known hypersensitivity to apremilast or to any of the excipients in the formulation.
Warnings and Precautions
Depression: Carefully weigh the risks and benefits of treatment with Otezla for patients with a history of depression and/or suicidal thoughts/behaviour, or in patients who develop such symptoms while on Otezla®. Patients, caregivers, and families should be advised of the need to be alert for the emergence or worsening of depression, suicidal thoughts or other mood changes, and they should contact their healthcare provider if such changes occur.
Psoriasis: Treatment with Otezla® is associated with an increase in adverse reactions of depression. During clinical trials, 1.3% (12/920) of patients treated with Otezla® reported depression compared to 0.4% (2/506) on placebo; 0.1% (1/1308) of Otezla® patients discontinued treatment due to depression compared with none on placebo (0/506). Depression was reported as serious in 0.1% (1/1308) of patients exposed to Otezla®, compared to none in placebo-treated patients (0/506). Suicidal behavior was observed in 0.1% (1/1308) of patients on Otezla®, compared to 0.2% (1/506) on placebo. One patient treated with Otezla® attempted suicide; one patient on placebo committed suicide.
Psoriatic Arthritis: During clinical trials, 1.0% (10/998) of patients treated with Otezla reported depression or depressed mood compared to 0.8% (4/495) treated with placebo; 0.3% (4/1441) of patients treated with Otezla® discontinued treatment due to depression or depressed mood compared with none in placebo treated patients (0/495). Depression was reported as serious in 0.2% (3/1441) of patients exposed to Otezla, compared to none in placebo treated patients (0/495). Suicidal ideation and behavior were observed in 0.2% (3/1441) of patients on Otezla, compared to none on placebo (0/495). Two patients who received placebo committed suicide compared to none on Otezla.
Weight Decrease: Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of Otezla.
Psoriasis: Body weight loss of 5-10% occurred in 12% (96/784) of patients treated with Otezla and in 5% (19/382) of patients treated with placebo. Body weight loss of ≥10% occurred in 2% (16/784) of patients treated with Otezla compared to 1% (3/382) of patients treated with placebo.
Psoriatic Arthritis: Body weight loss of 5-10% was reported in 10% of patients taking Otezla and in 3.3% of patients taking placebo. Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of Otezla.
Drug Interactions: Apremilast exposure was decreased when Otezla was
co-administered with rifampin, a strong
Psoriasis: Adverse reactions reported in ≥5% of patients were (Otezla%, placebo%): diarrhea (17, 6), nausea (17, 7), upper respiratory tract infection (9, 6), tension headache (8, 4), and headache (6, 4).
Psoriatic Arthritis: Adverse reactions reported in ≥2% of patients taking Otezla, that occurred at a frequency at least 1% higher than that observed in patients taking placebo, for up to 16 weeks (after the initial 5-day titration), were (Otezla%, placebo%): diarrhea (7.7, 1.6); nausea (8.9, 3.1); headache (5.9, 2.2); upper respiratory tract infection (3.9, 1.8); vomiting (3.2, 0.4); nasopharyngitis (2.6, 1.6); upper abdominal pain (2.0, 0.2).
Use in Specific Populations
Pregnancy and Nursing Mothers: Otezla is Pregnancy Category C; it has not been studied in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether apremilast or its metabolites are present in human milk. Caution should be exercised when Otezla is administered to a nursing woman.
Renal Impairment: Otezla dosage should be reduced in patients with severe renal impairment (creatinine clearance less than 30 mL/min); for details, see Dosage and Administration, Section 2, in the Full Prescribing Information.
Please click here
for Full Prescribing Information (
Psoriasis is an immune-mediated, non-contagious, inflammatory skin
disorder of unknown cause. The disorder is a chronic recurring condition
which varies in severity from minor localised 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.4 These patches, or plaques, frequently form on the
elbows, knees, lower back, and scalp.4 Psoriasis occurs
nearly equally in males and females18 and it affects many
aspects of patients' emotional and social well-being as well as daily
activities and the ability to study or work. In
About Psoriatic Arthritis
Psoriatic arthritis is a painful, chronic inflammatory disease characterised by pain, stiffness, swelling and tenderness of the joints, inflammation of specific ligaments and tendons, and decrease in physical functioning.20 It is estimated that nearly 38 million people worldwide have psoriatic arthritis.21,22 Psoriatic arthritis can impact the ability to perform day-to-day activities and has been reported to increase work disability. Enthesitis (inflammation at sites where tendons or ligaments insert into bone) and dactylitis (inflammation of fingers and toes, commonly known as "sausage fingers") are specific disease manifestations related to psoriatic arthritis.20
Celgene International Sàrl, located in Boudry, in the Canton of
This press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans," "will," "outlook" and similar expressions. Forward-looking statements are based on management's current plans, estimates, assumptions and projections, and speak only as of the date they are made. We undertake no obligation to update any 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 other reports filed with the Securities and Exchange Commission.
1 European Medicines Agency CHMP Positive Opinion Statement
2 Augustin M, Herberger K, Hintzen S, Heigel H, Franzke N, Shäfer I.
Prevalence of skin lesions and need for treatment in a cohort of 90880
5 Gladman DD. Psoriatic arthritis. Dermatologic Therapy, Vol. 22, 2009, 40-55
6 Papp K et al. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial. The Lancet, Volume 380, Issue 9843, Pages 738 - 746, 2012 doi:10.1016/S0140-6736(12)60642-4
7 Otezla Prescribing information (US Label) Available online: http://www.otezla.com/wp-content/uploads/2014/05/otezla-prescribing-information.pdf
8 Crowley, J. et al. Apremilast in Moderate to Severe Plaque Psoriasis: 32-Week Results in Patients With Nail, Scalp, and Palmoplantar Involvement (ESTEEM 2) [EADV 2014 abstract]
9 Yosipovitch, G.et al. Effects of Apremilast on Pruritus in Patients With Moderate to Severe Plaque Psoriasis: Results From the ESTEEM 1 and 2 Trials [EADV 2014 abstract]
10 Armstrong, A.W., et al. Quality of life and work productivity
impairment among psoriasis patients: findings from the
11 Kavanaugh A, et al. Ann Rheum Dis 2014;73:1020-1026. doi:10.1136/annrheumdis-2013-205056
12 Wells, A. et al. SAT0382: PALACE 4, A phase III, randomized, controlled trial of apremilast, an oral phosphodiesterase 4 inhibitor, for treatment of psoriatic arthritis: long-term (52-week) improvements in physical function [EULAR 2014 abstract]
13 Edwards, C. et al. SAT0389: Apremilast, an oral phosphodiesterase 4 inhibitor, is associated with long-term (52-week) improvements in enthesitis and dactylitis in patients with psoriatic arthritis: results from the PALACE 4 phase III, randomized, controlled trial [EULAR 2014 abstract]
14 Kavanaugh A, et al. Ann Rheum Dis 2014;73:1020-1026. doi:10.1136/annrheumdis-2013-205056
15 Kavanaugh A, et al. Abstract OP0078. Apremilast, an oral phosphodiesterase 4 inhibitor, is associated with long-term (52 week) improvement in measures of disease activity in patients with psoriatic arthritis: results from 3 phase III, randomized, controlled trials [EULAR 2014 abstract]
17 PH Schafer et al. Apremilast, a cAMP phosphodiesterase-4 inhibitor,
demonstrates anti-inflammatory activity in vitro and in a model of
20 Gottlieb A, Korman NJ, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol. 2008;58:851 864.
Celgene International Sàrl
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Source: Celgene International Sàrl
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