Shares of ACADIA Pharmaceuticals are up nearly 70% after the company announced it halted a Phase III psychosis trial early after its Parkinson’s disease drug Nuplazid hit primary endpoints and positioned the company to seek another potential regulatory approval.
This morning, San Diego-based ACADIA haled the HARMONY study assessing Nuplazid (pimavanserin) for the treatment of dementia-related psychosis. The company said the drug demonstrated a “highly statistically significant longer time to relapse” of psychosis with pimavanserin compared to placebo in a planned interim efficacy analysis. Following the early halt of the trial, ACADIA said it is planning to meet with the U.S. Food and Drug Administration in preparation of filing a supplemental New Drug Application. Also, the company said it intends to share the data from the HARMONY trial at upcoming medical meetings.
Nuplazid, a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors, was previously granted Breakthrough Therapy designation by the FDA. No drug has been approved by the FDA for the treatment of dementia-related psychosis. Nuplazid was previously approved by the FDA in 2016 for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis.
The HARMONY study was a 12-week stabilization study in which patients were treated with 34mg of Nuplazid daily. Following the stabilization period, patients who met pre-specified criteria for treatment response were randomized into the double-blind period of the study to continue their Nuplazid treatment or were switched to placebo. They were then followed for up to 26 weeks or until a relapse of psychosis occurred. The primary endpoint in the study was time to relapse in the double-blind period.
ACADIA President Serge Stankovic said the company is excited that the trial stoppage brings them one step closer to being able to offer patients with dementia-related psychosis a “critically needed treatment option.”
Approximately 30% of patients who have been diagnosed with a form of dementia suffer from psychoses, which commonly consisting of delusions and hallucinations. Dementia-related psychosis includes psychosis in Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease dementia, vascular dementia, and frontotemporal dementia. Serious consequences have been associated with severe or persistent psychosis in patients with dementia such as repeated hospital admissions, increased likelihood of nursing home placement, progression of dementia, and increased risk of morbidity and mortality.
Jeffrey Cummings, director emeritus of Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, said psychosis dramatically adds to the marked burden that dementia patients already carry. He added that the psychoses associated with dementia are among “the most challenging-to-manage aspects of the disease for caregivers.”
In July, Nuplazid failed to hit statistical significance in a Phase III schizophrenia trial. Patients in the ENHANCE trial showed a consistent trend in symptom improvement but did not hit statistical significance on the primary endpoint.
ACADIA 制药股价上涨近70%，此前该公司宣布，在帕金森病药物 Nuplazid 触及主要终点后，该公司提前终止了 III 期精神病试验，并将该公司定位于寻求另一项潜在的监管批准。
今天上午，圣地亚哥的 ACDIA 终止了 HARMONY 研究评估 Nuplazid （匹马万塞林）治疗痴呆相关精神病。该公司表示，在一项计划中的中期疗效分析中，与安慰剂相比，该药显示出“与吡万西林相比，精神疾病复发的时间具有高度统计学意义”。在试验早期停止后， ACDIA 表示，它计划与美国食品药品监督管理局（Food and Drug Administration）会面，准备提交一份补充新药申请。此外，该公司表示，打算在即将召开的医疗会议上分享 HARMONY 试验的数据。
Nuplazid 是一种选择性血清素逆激动剂和优先靶向5-HT2A 受体的拮抗剂，之前被 FDA 授予突破性治疗的称号。FDA 还没有批准任何治疗痴呆相关精神病的药物。Nuplazid 之前在2016年被 FDA 批准用于治疗与帕金森病精神病相关的幻觉和妄想。
HARMONY 研究是一项为期12周的稳定研究，患者每天服用34mg Nuplazid 。在稳定期之后，符合治疗反应预先指定标准的患者被随机分为双盲研究，继续他们的 Nuplazid 治疗或改用安慰剂。他们随后进行了长达26周的随访，直到精神病复发。研究的主要终点是双盲期复发的时间。
ACACADIA 总裁 Serge Stankovic 表示，该公司对试验停工感到兴奋，这使他们更接近能够向痴呆症相关精神病患者提供“亟需的治疗选择”。
拉斯维加斯克利夫兰诊所 Lou Ruvo 脑健康中心名誉主任 Jeffrey Cummings 说，精神疾病极大地增加了痴呆患者已经承受的负担。他补充说，与痴呆症相关的精神疾病是“护理人员最具挑战性的疾病管理方面”。
7月份， Nuplazid 未能在 III 期精神分裂症试验中达到统计学显著性。ENHANCE 试验的患者在症状改善方面表现出一致的趋势，但在主要终点没有达到统计学显著性。