The European Commission ( EC ) has granted marketing authorisation for Otezla ( Apremilast ), an oral selective inhibitor of phosphodiesterase 4 ( PDE4 ), in two therapeutic indications:
A) 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 ).
B) Alone or in combination with DMARDs ( disease modifying antirheumatic drugs ), for the treatment of active psoriatic arthritis ( PsA ) in adult patients who have had an inadequate response or who have been intolerant to a prior DMARD therapy.
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.
The marketing authorisation is based on efficacy and safety data from two phase III programs, ESTEEM and PALACE, which have demonstrated 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 ( 75% 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, 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 ( 20% 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 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.
Apremilast 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.
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.
The trial also consisted of 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% of all patients had received prior phototherapy and 54% had received prior conventional systemic and/or biologic therapy.
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 DMARDs, and/or biologics, with some patients who had previously failed a tumour necrosis factor ( TNF ) blocker.
Psoriasis is a systemic inflammatory condition characterised by raised scaly lesions on the skin. It affects approximately 14 million people across Europe and about 125 million people worldwide.
Plaque psoriasis, also called psoriasis vulgaris, is the most common form of the disease, representing approximately 80% of cases. Additionally, up to 30% of people with psoriasis may develop psoriatic arthritis.
Psoriatic arthritis, which is also an immune-mediated disease, is estimated to affect nearly 38 million people worldwide.
It is a chronic condition characterised by pain, stiffness, swelling and tenderness of the joints, and a decrease in physical functioning. ( Xagena )
Source: Celgene, 2015