ACADIA Pharmaceuticals announced top-line results from its Phase 3 CLARITY study which combined two identical studies evaluating the efficacy, safety and tolerability of pimavanserin as an adjunctive treatment for major depressive disorder (MDD). CLARITY study did not meet the prespecified combined efficacy and safety analysis.
CLARITY is a combination of CLARITY-2 and CLARITY-3, which were both 6-week, parallel-designed, randomized, double-blind, placebo-controlled, multi-center studies designed to evaluate the efficacy and safety of pimavanserin as adjunctive treatment in patients with MDD who have an inadequate response to standard antidepressant therapy with either a selective serotonin reuptake inhibitor (SSRI) or a serotonin norepinephrine reuptake inhibitor (SNRI). A total of 298 patients were randomized to receive six weeks of oral treatment with either 34 mg of pimavanserin or placebo, once daily, in addition to their ongoing antidepressant. The primary endpoint was change from baseline on the HAMD-17 total score. Statistical significance not achieved on the primary endpoint. Positive results were observed on the key secondary endpoint, the Clinical Global Impression – Severity (CGI-S) score, a clinician assessment of a patient’s severity of depression. Clinically meaningful separation was not achieved on the other secondary endpoints.
Similar rates of adverse events were observed between pimavanserin (58.1%) and placebo (54.7%). Adverse events reported in greater than 5% of patients on pimavanserin and greater than placebo were diarrhea, dry mouth and headache.
Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors. The serotonin system is thought to play an important role in neuropsychiatric disorders. In vitro, pimavanserin demonstrated no appreciable binding affinity for dopamine (including D2), histamine, muscarinic, or adrenergic receptors.
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.
About Major Depressive Disorder (MDD)
According to the National Institute of Mental Health, MDD affects approximately 17 million adults in the U.S., with approximately 2.5 million adults treated with adjunctive therapy. MDD is a condition characterized by depressive symptoms such as a depressed mood or a loss of interest or pleasure in daily activities for more than two weeks, as well as impaired social, occupational, or other important functioning. Continuing depression has been consistently linked with greater economic burden, with higher rate of healthcare utilization and reduced work productivity. The majority of people who suffer from MDD do not respond adequately to initial antidepressant therapy or discontinue due to side effects or safety concerns.