Date: 2015-01-16
Type of information: Granting of a Market Authorisation in the EU
Product name: Otezla®
Compound: apremilast
Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases
Action mechanism: phosphodiesterase inhibitor. Otezla® is an oral, small-molecule, selective inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels. Otezla® is the first in a new class of medicines for the treatment of both psoriasis and psoriatic arthritis, two diseases involving dysregulated immune system activity.
Company: Celgene (USA - NJ)
Disease: active psoriatic arthritis (PsA)
Latest news: * On January 16, 2015, Celgene announced that the European Commission (EC) has granted marketing authorisation for Otezla® (apremilast), the company's oral selective inhibitor of phosphodiesterase 4 (PDE4), for the treatment of active psoriatic arthritis. The marketing authorisation is based on efficacy and safety data from two Phase III programs, ESTEEM AND PALACE, which demonstrate a maintained clinical response among patients with psoriasis (ESTEEM) and psoriatic arthritis (PALACE) treated with Otezla® through 52 weeks, across multiple endpoints. In the ESTEEM studies, treatment resulted in significant and clinically meaningful improvements in plaque psoriasis as measured by PASI -75 (a 75 percent improvement in the Psoriasis Area Severity Index) scores at week 16, the primary endpoint. Patients on apremilast also benefited from significant improvements in difficult to treat areas, such as nail and scalp, and itch,1 known to have a marked impact on patients' quality of life and perception of disease severity. In the PALACE program, 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 American College of Rheumatology disease activity criteria) response at week 16, the primary endpoint. Patients on apremilast showed improvement across multiple disease manifestations specific to psoriatic arthritis, such as swollen and tender joints, dactylitis, enthesitis and overall physical function and quality of life.Consistently, across these Phase III clinical studies, the most commonly reported adverse reactions were diarrhoea, nausea, upper respiratory tract infection, tension headache and headache. Gastrointestinal (GI) adverse reactions were mostly mild to moderate in severity, with 0.3% of diarrhoea and 0.3% of nausea reported as being severe. These adverse reactions generally occurred within the first two weeks of treatment and usually resolved within four weeks. Overall, most adverse reactions were considered to be mild or moderate in severity. Otezla® will be launched in the European Union in the coming months in accordance with local requirements. Otezla® was approved on March 21, 2014 by the FDA for the treatment of adults with active psoriatic arthritis and on September 23, 2014 for the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. Marketing authorisation applications are ongoing in other countries, including Australia and Switzerland . * On 20 November 2014, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Otezla®, 10 mg, 20 mg, 30 mg, film-coated tabled intended for the treatment , alone or in combination with Disease Modifying Antirheumatic Drugs (DMARDs), of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior DMARD therapy and 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). The benefits with Otezla® in psoriatic arthritis are its ability to significantly improve the signs and symptoms of psoriatic arthritis, as assessed by the American college of rheumatology (ACR) 20 response criteria compared to placebo at Weeks 16. This ACR 20 response was maintained at Week 24. A pharmacovigilance plan for Otezla® will be implemented as part of the marketing authorisation. * On March 21, 2014, the FDA approved Otezla® (apremilast) to treat adults with active psoriatic arthritis (PsA). PsA is a form of arthritis that affects some people with psoriasis. Most people develop psoriasis first and are later diagnosed with PsA. Joint pain, stiffness and swelling are the main signs and symptoms of PsA. Currently approved treatments for PsA include corticosteroids, tumor necrosis factor (TNF) blockers, and an interleukin-12/interleukin-23 inhibitor. The safety and effectiveness of Otezla® were evaluated in three clinical trials involving 1,493 patients with active PsA. Patients treated with Otezla® showed improvement in signs and symptoms of PsA, including tender and swollen joints and physical function, compared to placebo. Patients treated with Otezla® should have their weight monitored regularly by a healthcare professional. If unexplained or clinically significant weight loss occurs, the weight loss should be evaluated and discontinuation of treatment should be considered. Treatment with Otezla was also associated with an increase in reports of depression compared to placebo. The FDA is requiring a pregnancy exposure registry as a post-marketing requirement to assess the risks to pregnant women related to Otezla® exposure. In clinical trials, the most common side effects observed in patients treated with Otezla® were diarrhea, nausea, and headache. A combined psoriatic arthritis/psoriasis Marketing Authorization Application (MAA) in Europe was submitted to health authorities in the fourth quarter of 2013.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2014-03-21
UE authorization: 2015-01-15
Favourable opinion UE: 2014-11-20
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
