信息分享，发现一支新的正在准备上市的新型单胺氧化酶B(MAO-B)抑制剂
Safinamide
Safinamide
Safinamide is an oral, once a day adjunctive therapy for any stage of Parkinson’s disease (PD). It is a unique molecule with a novel dual mechanism of action based on the enhancement of the dopaminergic function (through potent reversible inhibition of MAO-B and of dopamine uptake) and inhibition of the excessive release of glutamate.
Safinamide, has completed the Phase III development programme and filing for regulatory approval as add-on therapy in early and mid-to late PD patients in the EU and US is expected in Q4 2013.
Safinamide is partnered with Meiji Seika Pharma Co., Ltd., a subsidiary of the Meiji Holdings Co., Ltd., in Japan and key Asian territories and with Zambon Group in all other markets, including the US and Europe.
Results from the last out-standing Phase III studies, MOTION and SETTLE, have been presented during the 2013 American Academy of Neurology (AAN), the Mental Dysfunction & Other Non-Motor Features in Parkinson’s Disease and Related Disorders (MDPD) and the Movement Disease Society (MDS) annual meetings and conferences. The results confirmed earlier findings thatsafinamide significantly improves motor function in early Parkinson’s disease (PD) patients on a single dopamine agonist at a stable dose (MOTION study) andsignificantly improves motor fluctuations in mid-to late stage PD patients on levodopa and other PD drugs at a stable dose (SETTLE study).. Furthermore, both short (6 months) and long term (18 -24 months) treatment with safinamide has shown statistically significant improvement in Quality of Life, as assessed by the Parkinson’s disease Quality of Life (PDQ-39) and/or the European Quality of Life (EuroQoL, EQ-5D) scales.
The MOTION study was a six-month (24-week), randomized, double-blind, placebo controlled international Phase III trial. It enrolled patients with early idiopathic PD (less than five years of disease duration) treated with a stable dose of a single dopamine agonist for at least four weeks. 679 patients were randomized equally to receive once daily safinamide 50 mg, or 100 mg, or matching placebo tablets as adjunctive treatment to a single dopamine agonist at a fixed dose. In accordance with international regulatory guidelines, the primary efficacy variable of the trial was the change in motor symptoms assessed by the change in the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III score from baseline to week 24.
The SETTLE study was a six-month (24-week), randomized, double-blind, placebo controlled international Phase III trial. It enrolled 549 patients with mid-to late-stage idiopathic PD (more than three years of disease duration) treated with optimized, stable doses of levodopa and standard of care (dopamine agonist, COMT inhibitor, anticholinergic and/or amantadine) for at least four weeks. Patients who were experiencing a minimum of one and a half hours of “OFF” time during the day were randomized equally to treatment with once a day safinamide (50-100mg) or placebo (standard of care including levodopa), as adjunctive treatment. Based on discussions with the regulatory authorities, the primary endpoint of the trial was the change in daily “ON” time, as assessed by the patient completed daily diary cards (18 hours/day).
意大利Bresso市Newron制药公司顾问该项研究作者Ravi Anand说：“我们的超过两年的治疗周期的研究结果提示，safinamide联合左旋多巴和其他多巴胺治疗对那些持续存在震颤和不自主运动问题的患者有益，这些结果对于了解safinamide是如何影响重症帕金森病患者向前迈出了重要一步” 。
在为期两年的研究中，669名已在接受左旋多巴和多巴胺等治疗方法的中晚期帕金森病患者，随机接受每日50或100毫克的safinamide或安慰剂治疗。科学家利用联合国帕金森病评定量表来对受试者的运动能力进行测试，其测量活动包括如震颤、言语、行为、情绪和日常活动（包括吞咽、穿衣和走路）。运动障碍严重程度（DRS）利用一个特定工具进行测量，其作为主要疗效终点。
在研究初始，50毫克safinamide组患者平均分是3.9，而安慰剂药组患者则为3.4，100毫克safinamide组患者平均分为3.7。
两年后，研究人员在事后分析中发现，在接受左旋多巴治疗的基础上，每天服用100毫克safinamide的患者，其运动障碍或不自主运动问题有所减少。与安慰剂组患者相比，那些在研究初始运动障碍评定量表得分为4或更高的患者中，1/3其运动障碍或不自主运动问题减少了24%。50毫克剂量组中未发现显著差异。
在研究总体中，主要疗效测量（运动控制，即运动障碍）得分无显著差异。3个治疗组中副作用相当。
该研究由Newron/日内瓦默克雪兰诺国际S.A.资助。
