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 - Dermatological 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: patients with moderate to severe plaque psoriasis for whom phototherapy or systemic therapy is appropriate
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 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 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 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 plaque psoriasis are its ability to significantly improve moderate to severe plaque psoriasis as demonstrated by the proportion of patients with Psoriasis Area and Severity Index score (PASI)-75 and sPGA responses at Week 16, compared to placebo. * On September 23, 2014, Celgene announced that the FDA has approved Otezla® (apremilast), the Company\'s oral, selective inhibitor of phosphodiesterase 4 (PDE4), for the treatment of patients with moderate to severe plaque psoriasis for whom phototherapy or systemic therapy is appropriate. Otezla® is the first and only PDE4 inhibitor approved for the treatment of plaque psoriasis. Psoriasis, a chronic inflammatory disease of the skin resulting from an uncontrolled immune response, affects more than 125 million people worldwide. The approval of Otezla® was based primarily on safety and efficacy results from two multi-center, randomized, double-blind, placebo-controlled studies - ESTEEM 1 and ESTEEM 2 - conducted in adult patients with moderate to severe plaque psoriasis: body surface area (BSA) involvement of ≥10%, static Physician Global Assessment (sPGA) of ≥3 (moderate or severe disease), Psoriasis Area and Severity Index (PASI) score ≥12, and candidates for phototherapy or systemic therapy.
In the ESTEEM studies, Otezla® treatment resulted in significant and clinically meaningful improvements in plaque psoriasis as measured by PASI scores at week 16. Clinical improvement as measured by sPGA scores of clear to almost clear were also demonstrated in both studies.
The safety of Otezla® was assessed in 1,426 patients from three clinical trials. Side effects of Otezla® were diarrhea, nausea, upper respiratory tract infection, tension headache, and headache. Before starting Otezla®, patients should inform their doctor if they have a history of depression or suicidal behavior and if these conditions or other mood changes develop or worsen while taking Otezla®. Patients taking Otezla® should have their weight checked regularly.
Otezla® was approved on March 21, 2014 by the FDA for the treatment of adults with active psoriatic arthritis. A New Drug Submission (NDS) for psoriatic arthritis was submitted to health authorities in Canada in the second quarter of 2013. A NDS for psoriasis in Canada as well as a combined psoriatic arthritis/psoriasis Marketing Authorization Application (MAA) in Europe were all 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: 2014-09-23
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:
