ACADIA Pharmaceuticals Announces Positive Top-line Results from ADVANCE Trial of Pimavanserin as Treatment for Negative Symptoms of Schizophrenia
- Category: Small Molecules
- Published on Tuesday, 26 November 2019 15:49
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- ACADIA to initiate second pivotal study in the first half of 2020
SAN DIEGO, CA, USA I November 25, 2019 I ACADIA Pharmaceuticals Inc. (Nasdaq: ACAD), today announced positive top-line results from its ADVANCE study, a 26-week, randomized, double-blind, placebo-controlled study in 403 patients. ADVANCE evaluated the efficacy and safety of adjunctive pimavanserin treatment in patients with predominantly negative symptoms of schizophrenia who have achieved adequate control of positive symptoms with their existing antipsychotic treatment. No drug is approved by the FDA for the treatment of the negative symptoms of schizophrenia.
Pimavanserin demonstrated a statistically significant improvement on the study’s primary endpoint, the change from baseline to week 26 on the Negative Symptom Assessment-16 (NSA-16) total score, compared to placebo (-10.4 vs. -8.5; p=0.043; effect size = 0.21). A greater improvement in the NSA-16 total score compared to placebo was observed in the 53.8% of patients (n=107) who received the highest pimavanserin dose of 34 mg (-11.6 vs. -8.5; unadjusted p=0.0065, effect size = 0.34). In this study, pimavanserin did not separate from placebo on the key secondary endpoint, the Personal and Social Performance (PSP) scale.
ACADIA plans to commence a second pivotal study with the 34 mg dose of pimavanserin in the first half of 2020. Additional results from the ADVANCE study will be presented at future scientific meetings.
“The negative symptoms of schizophrenia such as social withdrawal, apathy, anhedonia, loss of motivation, blunted affect, and restricted speech contribute significantly to low function levels, long-term disability, and increased caregiver burden,” said Dr. Henry A. Nasrallah, M.D., Professor of Psychiatry, Neurology, & Neuroscience, Director, Neuropsychiatry and Schizophrenia Programs, at the University of Cincinnati College of Medicine. “Historically, it has been a challenge for clinicians to treat and significantly improve the negative symptoms of schizophrenia. There are no FDA-approved treatments indicated for the treatment of the negative symptoms of schizophrenia and there remains a serious and significant unmet need.”
“The positive efficacy results and favorable tolerability profile of pimavanserin observed in the ADVANCE study represent an important step forward for patients and their families, given the lack of currently approved treatment options for the negative symptoms of schizophrenia,” said Serge Stankovic, M.D., M.S.P.H., ACADIA's President. “We are pleased with the positive efficacy findings in this difficult to treat patient population and identified the 34 mg dose as demonstrating greater efficacy with favorable tolerability. We look forward to initiating a second pivotal study with the 34 mg dose during the first half of 2020.”
In the study, pimavanserin was well-tolerated with high completion rates of approximately 86% in both the pimavanserin and placebo treatment groups and similar rates of adverse events between pimavanserin (39.8%) and placebo (35.1%). Additionally, no clinically significant differences in vital signs, weight, metabolic syndrome or extrapyramidal symptoms were observed in the pimavanserin group compared to placebo. Serious adverse events were reported in 2.0% of patients on pimavanserin and 0.5% of patients on placebo and discontinuations due to adverse events were also low, 5.0% for pimavanserin and 3.0% for placebo.
The Phase 2 ADVANCE study was a 26-week, randomized, double-blind, placebo-controlled, multi-center, international study designed to examine the efficacy and safety of pimavanserin in patients with schizophrenia who have predominant negative symptoms while on a stable background antipsychotic therapy. 403 patients were randomized to receive once-daily pimavanserin (n=201) or placebo (n=202) as an adjunct treatment to their ongoing antipsychotic in a flexible dosing regimen. The starting daily dose of 20 mg of pimavanserin at baseline could have been adjusted to 34 mg or 10 mg during the first eight weeks of treatment. 53.8% of patients who were randomized to receive pimavanserin completed the trial on 34 mg, 44.7% on 20 mg, and 1.5% on 10 mg. The primary endpoint of the study was the change from baseline to week 26 on the Negative Symptom Assessment-16 (NSA-16) total score.
Baseline characteristics were similar across two treatment arms. The most prevalent background antipsychotics in the study included risperidone (38.5%), aripiprazole (32.5%), and olanzapine (28.0%). The average age of patient in the study was 37.2 years.
Conference Call and Webcast Information
ACADIA will discuss top-line results from its ADVANCE study of pimavanserin for adjunctive treatment for the negative symptoms of schizophrenia via conference call and webcast today at 5:00 p.m. Eastern Time. The conference call can be accessed by dialing 855-638-4820 for participants in the U.S. or Canada and 443-877-4067 for international callers (reference passcode 5696604). A telephone replay of the conference call may be accessed through December 2, 2019 by dialing 855-859-2056 for callers in the U.S. or Canada and 404-537-3406 for international callers (reference passcode 5696604). The conference call will also be webcast live on ACADIA’s website, www.acadia-pharm.com, in the investors section and archived until December 25, 2019.
Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors. These receptors are thought to play an important role in psychosis, schizophrenia, depression and other neuropsychiatric disorders. In vitro, pimavanserin demonstrated no appreciable binding affinity for dopamine (including D2), histamine, muscarinic, or adrenergic receptors. ACADIA is evaluating pimavanserin in an extensive clinical development program across multiple indications with significant unmet need including dementia-related psychosis, adjunctive major depressive disorder, and the negative symptoms of schizophrenia. Pimavanserin was approved for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis by the U.S. Food and Drug Administration in April 2016 under the trade name NUPLAZID®. NUPLAZID is not approved for dementia-related psychosis, schizophrenia or major depressive disorder.
About Schizophrenia and Negative Symptoms
According to the National Mental Health Institute, approximately one percent of the U.S. population develops schizophrenia during their lifetime1. Schizophrenia is a chronic, debilitating and often progressive mental illness characterized by disturbances in thinking, emotional reaction, and behavior. These disturbances may include positive symptoms, such as hallucinations and delusions, and a range of negative symptoms, including loss of interest, emotional withdrawal, and cognitive disturbances.
Studies show that about 40 to 50 percent of schizophrenia patients suffer from predominant negative symptoms2. While currently available antipsychotic treatments for schizophrenia target positive symptoms, most patients remain functionally impaired because of negative symptoms, cognitive deficits, and limited social function.
About ACADIA Pharmaceuticals
ACADIA is a biopharmaceutical company focused on the development and commercialization of innovative medicines to address unmet medical needs in central nervous system disorders. ACADIA has developed and commercialized the first and only medicine approved for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. ACADIA also has ongoing clinical development efforts in additional areas with significant unmet need, including dementia-related psychosis, schizophrenia, major depressive disorder, and Rett syndrome. This press release and further information about ACADIA can be found at: www.acadia-pharm.com.
1NAMI, Mental Help, PsyCom, SAMHSA study, NIMH data consolidation.
2Patel et al. 2015; Haro et al. 2015; Bobes et al. 2010; Chue and Lalonde, 2014.
SOURCE: ACADIA Pharmaceuticals