2014年11月27日讯 /生物谷BIOON/ --生物技术巨头新基（Celgene）重磅药物Otezla（apremilast）近日在欧盟监管方面收获好消息，欧洲药品管理局（EMA）人用医药产品委员会（CHMP）已建议批准Otezla，用于2种适应症。欧盟委员会（EC）通常都会采纳CHMP的意见，这意味着Otezla将在未来2-3个月在欧盟获批上市。
在美国，FDA分别于2014年3月和9月批准Otezla用于活动性银屑病关节炎（PsA）及中度至重度斑块型银屑病（plaque psoriasis）适应症。
在欧盟，具体而言，CHMP已批准Otezla：（1）用于对其他系统疗法（包括环孢素、甲氨蝶呤或补骨脂素紫外线疗法（PUVA））治疗无响应、有禁忌或不耐受的中度至重度慢性斑块型银屑病（plaque psoriasis）成人患者的治疗；（2）作用单药或联合其他疾病修饰抗风湿药物（DMARDs）用于对先前DMARD疗法响应不足或已经不能耐受的活动性银屑病关节炎（PsA）成人患者的治疗。
Otezla是一种口服、选择性磷酸二酯酶4（PDE4）抑制剂，该药是FDA批准的首个也是唯一一个用于斑块型银屑病治疗的PDE4抑制剂，为广泛的斑块型银屑病患者群体提供了一种有价值的治疗选择，包括以前使用过生物制剂或常规系统性药物治疗的患者群体。
银屑病（psoriasis）是一种由不受控免疫反应导致的皮肤慢性炎症性疾病，欧洲患者总数约为1400万例，全球患者总数超过1.25亿例。斑块型银屑病（plaque psoriasis）是最常见的疾病形式，约占银屑病病例的80%。约30%的银屑病患者可能发展为银屑病关节炎（PsA）。
Otezla销售峰值超20亿美元
业界认为，尽管面临着注射型药物肿瘤坏死因子（TNF）抑制剂的竞争，尤其是艾伯维的Humira（阿达木单抗）和辉瑞/安进的Entrel（etanercept），但Otezla用药不需要常规的实验室监测，而且该药是一种口服药物，相比市售药物，Otezla具有巨大优势，将为患者和医生提供一种重要的治疗选择。
EvaluatePharma此前预测，Otezla在2018年的销售额将达到12.19亿美元，而此次FDA批准Otezla新适应症，业界预期，Otezla的销售峰值有望突破20亿美元。
关于Otezla（apremilast）：
Otezla（apremilast）是一种口服小分子磷酸二酯酶(PDE4)抑制剂，在细胞内调控促炎症和抗炎介质的网络。PDE4是一种环磷酸腺苷(cAMP)特异性PDE，是炎性细胞中主要的PDE。PDE4抑制可提升细胞内cAMP水平，通过调控TNF-α、IL-23和其他炎性细胞因子的表达相应下调炎性反应。cAMP升高也会增加抗炎细胞因子，例如IL-10。
英文原文：Celgene Receives Positive CHMP Opinion for OTEZLA® (apremilast), the First Oral PDE4 Inhibitor for the Treatment of Patients with Psoriasis and Psoriatic Arthritis
BOUDRY, Switzerland--(BUSINESS WIRE)-- Celgene International Sàrl (NASDAQ: CELG), a wholly-owned subsidiary of Celgene Corporation, today announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for OTEZLA® (apremilast), the Company's oral selective inhibitor of phosphodiesterase 4 (PDE4), in two therapeutic indications:
——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 (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior DMARD therapy.
Psoriasis is an immune mediated skin condition characterised by raised scaly lesions on the skin. It affects approximately 14 million people across Europe2 and about 125 million people worldwide.3 Plaque psoriasis, also called psoriasis vulgaris, is the most common form of the disease, representing about 80 percent of cases.4 Up to 30 percent of people with psoriasis may develop psoriatic arthritis, which involves pain and swelling in jointsand other manifestations and may lead to significant disability.
"This CHMP positive opinion is an important step forward for people with psoriasis and psoriatic arthritis in Europe. These immune mediated diseases are frequently debilitating and cause severe physical and emotional pain to the individual," stated Tuomo Pätsi, President, Celgene Europe, the Middle East and Africa (EMEA). "We are proud to have moved one step closer to offering patients OTEZLA®, a new, oral treatment approach that could significantly help control their symptoms and make a considerable difference to their quality of life."
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 PASI-75 (a 75 percent improvement in the Psoriasis Area Severity Index) scores at week 16, the primary endpoint.6,7 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.8,9,10
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 American College of Rheumatology disease activity criteria) response at 16 weeks, the primary endpoint. 7,11 Patients on apremilast showed improvement across multiple disease manifestations specific to psoriatic arthritis, such as swollen and tender joints, as well as dactylitis, enthesitis and overall physical function.12,13,14
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 March 21, 2014 by the U.S. Food and Drug Administration (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. In Canada, OTEZLA was approved for the treatment of moderate-to-severe plaque psoriasis in November 2014. A New Drug Submission (NDS) for psoriatic arthritis was submitted to Canadian Health Authorities in the second quarter of 2013. Marketing authorisation applications are ongoing in other countries, including Australia and Switzerland.
The European Commission, which generally follows the recommendation of the CHMP, is expected to make its final decision within two to three months. If approval is granted, detailed conditions for the use of this product will be described in the Summary of Product Characteristics (SmPC), which will be published in the revised European Public Assessment Report (EPAR).
About OTEZLA®
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.