ACADIA Pharmaceuticals Inc.

About: ACADIA Pharmaceuticals Inc. is a company organization based out in San Diego, California, United States. It is known for research contribution in the topics: Pimavanserin & Receptor. The organization has 260 authors who have published 276 publications receiving 8418 citations.

A Novel Metal Iodide Promoted Three‐Component Synthesis of Substituted Pyrrolidines.

Abstract: (Matrix Presented) A new one-pot procedure for the synthesis of substituted pyrrolidine derivatives with commercially available cyclopropyl ketones, aldehydes, and amines by a metal iodide promoted three-component reaction was developed.

Triazadibenzoazulene compounds useful for the treatment and prevention of pain and screening methods therefor compounds useful for the treatment and prevention of pain and screening methods therefor

Abstract: The present invention relates to compounds having the generic structure (I): and to a method of treatment or prevention of pain using the above compounds.

Compounds useful for the treatment and prevention of pain and screening methods therefor

Abstract: The present invention relates to the composition of compounds having the generic structure: and to a method of treatment or prevention of pain using the above compounds.

427 - HARMONY study: pimavanserin significantly reduces risk of relapse of dementia-related psychosis

Abstract: Dementia-related psychosis (DRP) is common among patients with Alzheimer’s disease (AD), Parkinson’s disease (PD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and vascular dementia (VaD) and is associated with poor outcomes. HARMONY (NCT03325556) was a Phase 3, placebo-controlled, randomized, relapse-prevention study evaluating the efficacy and safety of pimavanserin for treating hallucinations and delusions associated with DRP. Patients with dementia and moderate-severe psychosis received open-label (OL) pimavanserin for 12 weeks. Patients with a sustained response (≥30% reduction in Scale for the Assessment of Positive Symptoms hallucinations+delusions Total Score AND Clinical Global Impression-Improvement score of much/very much improved) at Weeks 8 and 12 were randomized 1:1 to continue pimavanserin or receive placebo for up to 26 weeks in the double-blind (DB) period. The primary endpoint was time from randomization to relapse of DRP. 392 patients enrolled. 217 (61.8%) eligible patients experienced sustained response and were randomized. OL response was similar regardless of dementia subtype (randomization rates: 59.8% AD, 71.2% PDD, 71.4% VaD, 45.5% DLB, 50.0% FTD), baseline disease characteristics, age, dementia severity, or previous drug therapy. The study stopped early for superior efficacy when a prespecified interim analysis revealed >2.8-fold reduction in risk of relapse with pimavanserin (hazard ratio: 0.353; 95% CI: 0.172, 0.727; 1-sided p=0.0023). Adverse event rates were low and balanced (OL: 36.2%; DB: 41.0% pimavanserin, 36.6% placebo). No negative trends for worsening in cognition (as assessed by the Mini-Mental State Examination) or motor function were observed. The HARMONY study demonstrated a robust decrease in hallucinations and delusions and significant maintenance of efficacy with pimavanserin treatment in DRP. Study Sponsored By: ACADIA Pharmaceuticals Inc. Disclosures This study was funded by ACADIA Pharmaceuticals Inc. Drs. Foff, McEvoy, and Stankovic are all employees of ACADIA Pharmaceuticals Inc. (San Diego, CA, USA). Dr Cummings has provided consultation to ACADIA, Accera, Actinogen, AgeneBio, Alkahest, Allergan, Alzheon, Avanir, Axsome, Binomics, BiOasis Technologies, Biogen, Bracket, Cassava, Denali, Diadem, EIP Pharma, Eisai, Genentech, Green Valley, Grifols, Hisun, Idorsia, Lundbeck, Merck, Otsuka, Pain Therapeutics, Probiodrug, Proclara, QR, Resverlogix, Roche, Samumed, Shinkei Therapeutics, Sunovion, Suven, Takeda, and United Neuroscience pharmaceutical and assessment companies. He owns stock in ADAMAS, BioAsis, MedAvante, and QR Pharma. Dr. Cummings owns the copyright of the Neuropsychiatric Inventory (NPI). Dr. Cummings is supported by a COBRE grant from NIH/NIGMS #P20GM109025 and Keep Memory Alive. Dr. Soto has provided consultation to ACADIA, Avanir, Eisai, Lundbeck, and Otsuka.

T41. safety profile of adjunctive pimavanserin in the enhance study, a phase 3 trial for the potential treatment of schizophrenia in patients with an inadequate response to antipsychotic treatment

Abstract: Abstract Background Many patients with schizophrenia (SCZ) do not fully respond to antipsychotic (AP) treatment despite adherence and require augmentation, often with an AP with similar mode of action. Evidence supporting polypharmacy is limited and adding another AP increases associated risks of adverse effects, including extrapyramidal symptoms and cardiometabolic disturbances. Pimavanserin (PIM) is a highly selective serotonin 5-HT2A inverse agonist/antagonist approved for the treatment of Parkinson’s disease psychosis. The phase 3 ENHANCE study evaluated adjunctive PIM in patients with SCZ and inadequate response to their current AP. As previously reported (ACNP 2019), the primary efficacy endpoint of ENHANCE (change in Positive and Negative Syndrome Scale [PANSS] total score) did not achieve statistical significance. Other prespecified analyses did yield nominal statistical separation from placebo, including changes in PANSS Negative Symptoms subscale, and in PANSS total score for the subgroup of European patients. Here we describe key safety results. Methods ENHANCE was a 6-week, randomized, double-blind, placebo (PBO)-controlled study of adjunctive PIM in patients with SCZ and inadequate response to their prescribed AP (aripiprazole, olanzapine, risperidone, and others). Patients included were age 18–55 years with PANSS total score of ≥65 and ≤110, and scores of ≥4 on ≥2 items including delusions, hallucinatory behavior, and/or suspiciousness/persecution; Clinical Global Impression-Severity scale score ≥4 was also required. The starting dose of PIM or PBO was 20 mg daily and could be adjusted up to 34 mg or down to 10 mg daily after 1 week based on investigator discretion. Safety was evaluated in all randomized patients who received ≥1 dose of study drug. Results All 396 randomized patients (PIM, n=198; PBO, n=198) were included in the safety analysis set. Treatment-emergent adverse events (TEAEs) were reported in 39.9% and 36.4% of patients in the PIM and PBO groups, respectively; most frequent TEAEs were headache (PIM 6.6%, PBO 9.1%), somnolence (PIM 6.6%, PBO 3.5%), and insomnia (PIM 5.1%, PBO 3.5%). Changes from baseline in Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Scale global clinical assessment of akathisia (GCAA), and Simpson–Angus Scale (SAS) scores were similar in the PIM and PBO groups. No patient developed dyskinesia (defined as a score ≥3 on any, or ≥2 on 2 of the first 7 AIMS items). Akathisia (GCAA score ≥2) in patients without baseline akathisia occurred in 4/186 (2.2%) patients receiving PIM and 1/189 (0.5%) receiving PBO. Parkinsonism (SAS total score >3) in patients without Parkinsonism at baseline occurred in 3/181 (1.7%) patients receiving PIM and 4/182 (2.2%) receiving PBO. No patient in either treatment arm had QTcF prolongation >500 msec or Torsades de Pointes during the study period; 2 (1.1%) patients in the PIM arm and 0 in the PBO arm had post-baseline QTcF prolongation >60 msec. Hypotension was reported in 1 patient in each treatment group; no patient had clinically important changes from baseline in blood pressure during treatment. Weight increase ≥7% from baseline was reported in 5/189 (2.6%) patients in the PIM group and 3/191 (1.6%) in the PBO group. Mean changes from baseline in PIM and PBO groups for fasting glucose were 0.07 mmol/L and 0.01 mmol/L; for triglycerides were -0.007 mmol/L and -0.136 mmoL/L, and for cholesterol were -0.10 mmol/L and -0.03 mmol/L, respectively. Discussion Results of ENHANCE provide evidence that the addition of PIM to frequently used APs is well tolerated in patients with SCZ.