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—Nuplazid(pimavanserin)tablets获美国FDA批准伴随帕金森氏病治疗幻觉和妄想第一个药物
2016年4月29日，美国食品和药品监管局(FDA)批准Nuplazid(pimavanserin)片，第一个药物被批准治疗伴随精神病幻觉和妄想经受 帕金森氏病人们。
多至50%有帕金森氏病患者在他们疾病过程中在有些时候可能发生幻觉或妄想。经受这些的人们他们见到或听到不存在的事情(幻觉)和/或有错误想法(妄想)。有帕金森氏病经受幻觉和妄想是严重症状，和可导致思考力和情绪如此地损害人们可能是爱他们的相关亲人或他们采取适当照顾的亲人。
FDA的药品评价和研究中心中精神病产品部主任Mitchell Mathis，M.D.说：“幻觉和妄想可以深刻地令人不安和失能，”。“Nuplazid代表对有帕金森氏病经受这些症状人们的一个重要治疗。”
根据美国国家卫生院估计每年50,000美国人被诊断有帕金森氏病，和约一百万美国人有这种情况。神经学疾病典型地发生在超过60岁人们，当大脑中细胞产生一种化学物质被称为多巴胺[dopamine]变为受损害或死亡。多巴胺帮助大脑区域间传递信号产生光滑，有目的的运动 -- 像吃，书写或剃须。疾病的早期症状是细微和逐渐地发生。在有些帕金森氏病人们进展比其他人较迅速。当疾病进展，摇晃，或震颤，影响有帕金森氏病的多数人们，可能开始干扰每天活动。其他症状可能包括抑郁和其他情绪变化；幻觉和妄想；吞咽，咀嚼，和说话困难；尿问题或便秘；皮肤问题；和睡眠混乱。
在一项199例参加者6-周Nuplazid的有效性临床试验。Nuplazid被显示减低幻觉和妄想和/或严重程度帕金森氏病的无主要运动症状频数优于安慰剂。
如同其他非典型抗精神病药，Nuplazid有一个黑框警告警戒卫生保健专业人员伴随使用这些药物治疗有痴呆-相关精神病老年人们死亡风险增加。在治疗有痴呆-相关精神病患者没有药物被批准。
在临床试验中，服用Nuplazid参加者报道的最常见副作用为：肿胀，通常地槐，腿，和足由于组织中过量液体的积蓄(外周水肿)；恶心；和精神异常状态(混乱状态)。
Nuplazid被授予对伴随帕金森氏病幻觉和妄想治疗的突破性治疗指定。突破性治疗指定是一种程序被设计加快开发和审评意向治疗一种严重情况和其中初步临床证据表明药物对一个临床上有意义终点可能显示实质上超过可得到的改善。药物还授予优先审评。FDA的优先审评程序对一种严重情况的安全性或有效性治疗，预防或诊断提供显著改善药物加快审评。
Nuplazid是由加州，圣地亚哥Acadia制药公司上市。
Nuplazid (pimavanserin)tablets
NUPLAZID™ (pimavanserin) is the first and only medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis.
According to the National Parkinson Foundation, about one million people in the United States and from four to six million people worldwide suffer from Parkinson’s disease. An estimated 40 percent of these patients have Parkinson’s disease psychosis, a debilitating condition that is characterized by hallucinations and delusions, is associated with significant caregiver burden, and is a major reason for nursing home placement among Parkinson’s patients.
We invite you to visit our product website for NUPLAZID™ for more information and full prescribing information. The product information is for U.S. residents only.
Important Safety Information and Indication for NUPLAZID™ (pimavanserin) tablets
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. NUPLAZID is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson’s disease psychosis.
INDICATIONS AND USAGE
NUPLAZID is an atypical antipsychotic indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis.
QT Interval Prolongation: NUPLAZID prolongs the QT interval. The use of NUPLAZID should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong QT interval including Class 1A antiarrhythmics or Class 3 antiarrhythmics, certain antipsychotic medications, and certain antibiotics. NUPLAZID should also be avoided in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and presence of congenital prolongation of the QT interval.
Adverse Reactions: The most common adverse reactions (≥2% for NUPLAZID and greater than placebo) were peripheral edema (7% vs 2%), nausea (7% vs 4%), confusional state (6% vs 3%), hallucination (5% vs 3%), constipation (4% vs 3%), and gait disturbance (2% vs <1%).
Drug Interactions: Strong CYP3A4 inhibitors (eg, ketoconazole) increase NUPLAZID concentrations. Reduce the NUPLAZID dose by one-half.
Strong CYP3A4 inducers may reduce NUPLAZID exposure, monitor for reduced efficacy. Increase in NUPLAZID dosage may be needed.
Renal Impairment: No dosage adjustment for NUPLAZID is needed in patients with mild to moderate renal impairment. Use of NUPLAZID is not recommended in patients with severe renal impairment.
Hepatic Impairment: Use of NUPLAZID is not recommended in patients with hepatic impairment. NUPLAZID has not been evaluated in this patient population.
Pediatric Use: Safety and efficacy have not been established in pediatric patients.
Dosage and Administration: Recommended dose: 34 mg per day, taken orally as two
New Drugs Online Report for pimavanserin
Information
Generic Name: pimavanserin
Trade Name: Nuplazid
Entry Type: New molecular entity
Development and Regulatory status
UK: Phase III Clinical Trials
EU: Phase III Clinical Trials
US: Approved (Licensed)
UK launch Plans: Available only to registered users
Actual UK launch date:
Comments
Mar 16: the US FDA Psychopharmacologic Drugs Advisory Committee has voted 12 to 2 in favour of approval. Advisory Committee recommendations are normally followed by the FDA, which will make a final decision on approval by 1st May [15].
01/04/2016 15:36:02
Oct 15: FDA grans priority for review status. A decision is expected by may 2016 [14].
04/11/2015 09:36:27
Sept 15: ACADIA Pharmaceuticals announced it has submitted a New Drug Application (NDA) to the US FDA seeking approval for NUPLAZID™ (pimavanserin) for psychosis associated with Parkinson’s disease [13].
04/09/2015 09:11:46
Mar 15: Company announce that it had shifted it´s plan to submit NDA to the second half of 2015 [12].
13/03/2015 17:26:44
Sep 14: The FDA has granted Breakthrough Therapy designation to NUPLAZID™ (pimavanserin) for the treatment of Parkinson’s disease psychosis. There are plans to submit the NDA to the FDA near the end of this year. [11]
03/09/2014 12:07:47
Apr 13: The FDA has agreed that the data from the pivotal PIII -020 study, together with supportive data from other studies are sufficient to support the filing of a New Drug Application (NDA) for the treatment of Parkinson’s disease psychosis. ACADIA will no longer conduct the PIII -021 study that was planned as a confirmatory trial and was scheduled to start later this month. The company plan to file in the US in late 2014 [9]
11/04/2013 21:55:22
Jul 10: New PIII trial started [4].
31/07/2010 17:35:54
May 09: currently being investigated in 2 PIII studies (1)
04/05/2009 18:30:25
Trial or other data
Feb 14: PIII 020 Study published in Lancet 2014 Feb 8; 383: 533
11/02/2014 15:06:10
Nov 13: Data published from pivotal Phase III -020 Study in the November 1, 2013 online issue of The Lancet [10]
04/11/2013 12:12:17
Mar 13: Acadia Pharmaceutcials announces detailed results from the pivotal PIII -020 study. Pimavanserin met the primary endpoint by demonstrating highly significant antipsychotic efficacy on the 9-item SAPS-PD scale (p=0.001). Pimavanserin also met secondary endpoints for motoric tolerability as measured using Parts II and III of the Unified Parkinson´s Disease Rating Scale (UPDRS), the Clinical Global Impression Severity (CGI-S) scale (p<0.001), the Clinical Global Impression Improvement (CGI-I), scale (p=0.001), and a CGI-I responder analyses (p=0.002). The CGI-I responder results showed that approximately twice as many subjects in the pimavanserin treatment arm vs. placebo were rated as very much improved or much improved at the conclusion of the study. In addition, pimavanserin demonstrated significant improvements using the full 20-item SAPS scale and each of the separate hallucinations and delusions domains in supportive analyses. Statistically significant benefits were also observed in exploratory measures of nighttime sleep, daytime wakefulness, and caregiver burden [8].
21/03/2013 16:51:04
Dec 12: Following positive results from a PIII study, Acadia has won finance for a PIII confirmatory study [7].
12/12/2012 18:51:06
Nov 12: Acadia Pharmaceuticals announces successful top-line results from its pivotal PIII trial evaluating efficacy, tolerability & safety of pimavanserin in pts with PDP. Pimavanserin met the primary endpoint with a 5.79 point improvement in psychosis at day 43 vs. a 2.73 point improvement for placebo on SAPS-PD (difference 3.06 points; p=0.001). Pimavanserin also met the key secondary endpoint for motoric tolerability as measured using Parts II & III of the Unified PD Rating Scale, (UPDRS). These results were further supported by a highly significant improvement in the secondary efficacy measure, the Clinical Global Impression Improvement (CGI-I) scale (p=0.001). In addition, clinical benefits were observed in all exploratory efficacy measures with significant improvements in nighttime sleep, daytime wakefulness & caregiver burden. Most common adverse events were urinary tract infection (11.7% placebo vs. 13.5% Pima vanserin) & falls (8.5% vs. 10.6%, respectively). AEs were generally mild to moderate. The only serious AEs that occurred in more than one pt were UTI (1 vs. 3) & psychotic disorder (0 vs. 2), respectively. 90% of pts who completed the clinical phase of this trial elected to roll over into the ongoing open-label safety extension study [6].
28/11/2012 08:53:37
Oct 10: Acadia Pharmaceuticals and Biovail have ended the collaboration agreement on pimavanserin. Acadia has regained all rights to pimavanserin and plans to continue PIII studies for Parkinson´s, but won´t pursue development for Alzheimer´s or schizophrenia [5].
29/10/2010 16:03:48
Oct 09: Acadia and Biovail have decided to conduct a third PIII trial for PDP even though a previous PIII study failed last month. They will use the findings from the failed study along with the data from a second, ongoing PIII study to design the third trial, due to start H1 2010. The study will use a 40mg dose of pimavanserin [3].
06/10/2009 21:42:32
Sep 09: Pimavanserin failed to achieve the primary endpoint of antipsychotic efficacy according to the top-line results from the first pivotal PIII trial in 298 patients with Parkinson´s disease psychosis (PDP). The 6-week study randomized patients to one of three arms (pimavanserin 10 mg or 40 mg, or placebo, daily) while remaining on stable doses of their existing anti-Parkinson´s therapy. The primary endpoint was measured using the hallucinations and delusions domains of the Scale for the Assessment of Positive Symptoms (SAPS). There was a marked reduction in SAPS scores in all arms: 5.9 points in the placebo arm, 5.8 points in the 10 mg pimavanserin arm, and 6.7 points in the 40 mg pimavanserin arm. Statistical significance was not achieved in either pimavanserin arm primarily due to the larger than expected improvement in placebo-treated patients. Pimavanserin met the secondary endpoint of motoric tolerability as measured using the Unified Parkinson´s Disease Rating Scale (UPDRS) and was well tolerated, with the frequency of adverse events generally similar across all study arma [2].
01/09/2009 19:45:16
Evidence Based Evaluations
NIHR HSRIC http://www.hsric.nihr.ac.uk/topics/pimavanserin-tartrate-for-psychosis-associated-with-parkinsons-disease-first-line/
References
Available only to registered users
Category
BNF Category: Drugs used in psychoses and related disorders (04.02)
Pharmacology: selective 5-HT2A inverse agonist
Epidemiology: Up to 40% of patients with PD may develop psychotic symptoms, commonly visual hallucinations and delusions (1)
Indication: Parkinson's disease
Additional Details: psychosis
Method(s) of Administration
Oral
Company Information
Name: Acadia
US Name: Acadia
Further Information
Anticipated commissioning route (England) -
High cost drug list? Awaiting Update
Implications Available only to registered users
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm498442.htm
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