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.

Evaluation of the safety, tolerability, and efficacy of pimavanserin versus placebo in patients with Alzheimer's disease psychosis: a phase 2, randomised, placebo-controlled, double-blind study

Abstract: Summary Background Pimavanserin is a selective 5-HT 2A receptor inverse agonist and antagonist approved in the USA for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis No safe or effective pharmacological treatment is approved for psychosis in patients with Alzheimer's disease Therefore, we aimed to evaluate the safety, tolerability, and efficacy of pimavanserin versus placebo in patients with Alzheimer's disease psychosis Methods We did a phase 2, randomised, double-blind, placebo-controlled, single-centre (with multiple affiliated nursing home sites across the UK) study We included participants of either sex who were aged 50 years or older with possible or probable Alzheimer's disease and psychotic symptoms including visual or auditory hallucinations, delusions, or both Participants were randomly assigned (1:1) to 12 weeks of oral treatment with either pimavanserin (two 17 mg tablets daily) or placebo, with use of permuted block sizes of four and stratified by baseline Mini-Mental State Examination (MMSE) total score ( Findings Between Jan 16, 2014, and Oct 27, 2016, 345 participants across 133 nursing homes were screened, of whom 181 were randomly assigned treatment (n=90 pimavanserin and n=91 placebo) 178 participants were included in the modified intention-to-treat population Mean total baseline NPI–NH psychosis scores were 9·5 (SD 4·8) for the pimavanserin group and 10·0 (5·6) for the placebo group Mean change in the NPI–NH psychosis score at week 6 was −3·76 points (SE 0·65) for pimavanserin and −1·93 points (0·63) for placebo (mean difference −1·84 [95% CI −3·64 to −0·04], Cohen's d =−0·32; p=0·045) By week 12, no significant advantage for pimavanserin versus placebo was observed for the overall study population (treatment difference −0·51 [95% CI −2·23 to 1·21]; p=0·561) Common adverse events were falls (21 [23%] of 90 participants in the pimavanserin group vs 21 [23%] of 91 in the placebo group), urinary tract infections (20 [22%] vs 25 [28%]), and agitation (19 [21%] vs 13 [14%]) Eight (9%) participants on pimavanserin and 11 (12%) on placebo discontinued treatment because of adverse events No detrimental effect was observed on cognition or motor function in either group Interpretation Pimavanserin showed efficacy in patients with Alzheimer's disease psychosis at the primary endpoint (week 6) with an acceptable tolerability profile and without negative effect on cognition Further follow-up to week 12 did not show significant advantage for pimavanserin versus placebo Funding ACADIA Pharmaceuticals

Human anti-anthrax protective antigen neutralizing monoclonal antibodies derived from donors vaccinated with anthrax vaccine adsorbed

Abstract: Potent anthrax toxin neutralizing human monoclonal antibodies were generated from peripheral blood lymphocytes obtained from Anthrax Vaccine Adsorbed (AVA) immune donors The anti-anthrax toxin human monoclonal antibodies were evaluated for neutralization of anthrax lethal toxin in vivo in the Fisher 344 rat bolus toxin challenge model Human peripheral blood lymphocytes from AVA immunized donors were engrafted into severe combined immunodeficient (SCID) mice Vaccination with anthrax protective antigen and lethal factor produced a significant increase in antigen specific human IgG in the mouse serum The antibody producing lymphocytes were immortalized by hybridoma formation The genes encoding the protective antibodies were rescued and stable cell lines expressing full-length human immunoglobulin were established The antibodies were characterized by; (1) surface plasmon resonance; (2) inhibition of toxin in an in vitro mouse macrophage cell line protection assay and (3) in vivo in a Fischer 344 bolus lethal toxin challenge model The range of antibodies generated were diverse with evidence of extensive hyper mutation, and all were of very high affinity for PA83~1 × 10-10-11M Moreover all the antibodies were potent inhibitors of anthrax lethal toxin in vitro A single IV dose of AVP-21D9 or AVP-22G12 was found to confer full protection with as little as 05× (AVP-21D9) and 1× (AVP-22G12) molar equivalence relative to the anthrax toxin in the rat challenge prophylaxis model Here we describe a powerful technology to capture the recall antibody response to AVA vaccination and provide detailed molecular characterization of the protective human monoclonal antibodies AVP-21D9, AVP-22G12 and AVP-1C6 protect rats from anthrax lethal toxin at low dose Aglycosylated versions of the most potent antibodies are also protective in vivo, suggesting that lethal toxin neutralization is not Fc effector mediated The protective effect of AVP-21D9 persists for at least one week in rats These potent fully human anti-PA toxin-neutralizing antibodies are attractive candidates for prophylaxis and/or treatment against Anthrax Class A bioterrorism toxins