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Celgene’s Otezla® (Apremilast) receives European Marketing Authorisation

Posted: 19 January 2015 |

An oral therapy for moderate-to-severe chronic plaque psoriasis and active psoriatic arthritis, with no drug-specific pre-screening or laboratory monitoring requirements…

Celgene

Celgene UK announced today that the European Commission has licensed Otezla®, the Company’s oral selective inhibitor of phosphodiesterase 4 (PDE4), in two therapeutic indications:2

  • For the treatment of moderate-to-severe chronic plaque psoriasis in adult patients who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or psoralen and ultraviolet-A light (PUVA).
  • Alone or in combination with Disease Modifying Antirheumatic Drugs (DMARDs), for the treatment of active psoriatic arthritis in adult patients who have had an inadequate response or who have been intolerant to a prior DMARD therapy.

In clinical studies, Otezla® demonstrated significant improvements in psoriatic skin plaques (PASI 75) at week 16 versus placebo.3 One third of patients in the Otezla® treated group achieved this primary endpoint.4 In addition, Otezla® demonstrated a treatment benefit across multiple manifestations of psoriasis, including itch, nail and scalp involvement, and quality of life measures.1 In patients with psoriatic arthritis, Otezla® demonstrated significant improvement in ACR 20 at week 16, with twice as many patients treated with Otezla® achieving this primary endpoint versus placebo (37% v 19%).1 In addition, improvements in number of swollen joints, number of painful/tender joints, dactylitis, enthesitis and physical function were seen in the Otezla®-treated patients.1

“This decision marks an advance in the management of psoriasis and psoriatic arthritis. Apremilast is a new, oral treatment that fills a real gap in the therapies available for patients. An effective medication that doesn’t require regular monitoring will be welcomed by both patients and physicians,” stated Dr Chris Edwards, Consultant Rheumatologist, University Hospital Southampton NHS Foundation Trust.

Otezla® has a novel mechanism of action in psoriasis and psoriatic arthritis, offering a second line treatment option that does not require tuberculosis pre-screening or regular laboratory monitoring.2,3,5,6 Otezla® works by specifically targeting PDE4, which in turn elevates intracellular cAMP levels and helps to regulate the uncontrolled immune responses that cause the symptoms associated with psoriasis and psoriatic arthritis.7

Psoriasis can occur on any area of the body, including the scalp and under the nails. It affects approximately 1.3-2.6 percent of people in the UK.8 Up to 30 percent of people with psoriasis may develop psoriatic arthritis,9 which involves inflammation, pain and swelling in joints, and may lead to significant disability.10

Helen McAteer, Chief Executive of the Psoriasis Association commented: “People with moderate-severe psoriasis and/or psoriatic arthritis report that the conditions can often have a negative impact on their physical, mental and social lives. We also know, from our members, that they find current treatment options unappealing owing to both experienced and potential side effects, or the way in which the treatment is administered. A new, convenient treatment has long been sought.”

The Marketing Authorisation for Otezla®, issued by the European Commission, is based on data from the ESTEEM and PALACE studies.1 In the ESTEEM studies, which form the basis of approval for Otezla® in psoriasis, treatment resulted in significant and clinically meaningful improvements in plaque psoriasis versus placebo as measured by PASI-75 (a 75 percent improvement in the Psoriasis Area and Severity Index) scores at week 16, the primary endpoint.6

In the PALACE programme, which forms the basis for the approval of Otezla® in psoriatic arthritis, treatment resulted in significant and clinically meaningful improvements in the signs and symptoms of psoriatic arthritis versus placebo, as measured by the modified ACR-20 (a 20 percent improvement in the American College of Rheumatology disease activity criteria) response at 16 weeks, the primary endpoint.11

In the two phase III programmes, PALACE and ESTEEM, the clinical response to Otezla® was maintained through week 52 across multiple endpoints.6,12,13

Across the phase III clinical studies, the most commonly reported adverse reactions were diarrhoea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache and headache. 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 one month. Exposure-adjusted incidence rates of major adverse cardiac events, serious infections, including opportunistic infections, and malignancies, were comparable to placebo.14,15

“We are excited that this first approval from our growing Inflammation and Immunology pipeline may provide a much-needed treatment option for people with psoriasis or psoriatic arthritis. As Otezla® is an oral treatment and doesn’t require regular monitoring, it fills a long-standing treatment gap, offering an underserved patient population a new, convenient, effective option to help control their condition.” stated Wim Souverijns, General Manager, Celgene UK and Ireland.

Otezla® has been submitted for review by both the National Institute for Health and Care Excellence (NICE) and the Scottish Medicines Consortium (SMC) whose decisions are expected later this year.

  1. Otezla® Summary of Product Characteristics. Current version available online at www.medicines.org.uk.
  2. Reich K et al. Long-term Safety and Tolerability of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients With Moderate to Severe Psoriasis: Results From a Phase III, Randomized, Controlled Trial (ESTEEM 1). P8296. Presented at the 72nd Annual Meeting of the American Academy of Dermatology 2014; March 21-25;Denver, CO, USA.
  3. 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. Abstract P1682. Presented at the 23rd Congress of the European Academy of Dermatology and Venereology 2014; October 8-12; Amsterdam, the Netherlands
  4. Reich K, et al.  Apremilast, an Oral Phosphodiesterase 4 Inhibitor, In Patients with moderate to Severe Psoriasis: 16-Week Results of a Phase 3, Randomized, Controlled Trial (ESTEEM-1). Presented at the 71st Annual Meeting of the American Academy of Dermatology 2013; March 1-5; Miami Beach, USA
  5. Crowley J, et al. Apremilast in Moderate to Severe Plaque Psoriasis: 32-Week Results in Patients With Nail, Scalp, and Palmoplantar Involvement (ESTEEM 2). Abstract P1687. Presented at the 23rd Congress of the European Academy of Dermatology and Venereology 2014; October 8-12; Amsterdam, the Netherlands
  6. Paul C, et al. Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients With Moderate to Severe Psoriasis: Results of a Phase 3, Randomized, Controlled Trial (ESTEEM 2). Oral presentation at the 23rd Congress of the European Academy of Dermatology and Venereology 2014; October 8-12; Amsterdam, the Netherlands
  7. Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012;83:1583–1590.
  8. Parisi R, et al. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013;133(2):377-85 
  9. National Institute for Health and Care Excellence. Etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis. Technology appraisal guidance 199. August 2010.
  10. Gottlieb A, 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
  11. Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis. 2014;73:1020–1026
  12. Chimenti S, et al. Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients With Psoriatic Arthritis: Results of Phase 3, Randomized, Placebo-Controlled Trials (PALACE 1, 2, and 3). Abstract P1679. Presented at the 23rd Congress of the European Academy of Dermatology and Venereology 2014; October 8-12; Amsterdam, the Netherlands
  13. Papp K, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate to severe psoriasis: Results from the randomized treatment withdrawal phase of a phase 3, randomized, controlled trial (ESTEEM 1). Abstract P8359. Presented at 72nd Annual Meeting of the American Academy of Dermatology (AAD) 2014; March 21-25; Denver, CO, USA
  14. Mease PJ, et al. Long-term safety and tolerability of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis: pooled safety analysis of three phase 3, randomized, controlled trials. Poster 310. Presented at the 2013 ACR/ARHP annual meeting 2013; October 26-30; San Diego, CA
  15. Reich K, et al. Long-term Safety and Tolerability of Apremilast in Patients With Psoriasis: Pooled Safety Analysis of Two Phase 3, Randomized, Controlled Trials (ESTEEM 1 and 2). FC05.2. Presented at the 23rd Congress of the European Academy of Dermatology and Venereology 2014; October 8-12; Amsterdam, the Netherlands.

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