The selective serotonin inverse agonist, previously approved for Parkinson symptoms, could soon seek FDA approval as an adjunctive therapy.
Pimavanserin could soon be in position to reach the market for the treatment of major depressive disorder (MDD).
This week, Acadia Pharmaceuticals announced the launch of the phase 3 CLARITY Program, in which the efficacy and safety of pimavanserin as an adjunct therapy in patients with MDD who have had an inadequate response to standard antidepressant therapy.
CLARITY-2 and CLARITY-3 will be a pair of six-week, parallel, randomized, double-blind, placebo-controlled studies involving 280 US patients in first trial, then 280 international patients in the second trial. Both studies will randomize patients to either 6 weeks of oral 34 mg pimavanserin or once-daily placebo, plus ongoing antidepressant therapy. Investigators are assessing for a primary endpoint of change from baseline on the total score for the 17-item Hamilton Depression Rating Scale (HAMD-17).
Upon trial completion, patients will then be eligible to participate in a 52-week, open-label extension that assesses the long-term safety and tolerability of the drug.
If all goes well, positive findings from at least one of the trials could be coupled with phase 2 CLARITY results to comprise Acadia’s marketing application to the US Food and Drug Administration (FDA).
“The results observed in the original Phase 2 CLARITY study showed significant promise for patients with MDD, including a significant antidepressant response, improvement in disability, decreased daytime sleepiness, no meaningful weight gain, and improved sexual function,” ACADIA President Serge Stankovic, MD, MSP, said in a statement. “We believe pimavanserin has the potential to be a very important treatment option for the millions of MDD patients where there remains unmet medical need.”
Pimavanserin last made headlines in September, when the FDA cleared the marketed form of the drug Nuplazid from any association with deaths or serious adverse events (SAEs) in treated patients with Parkinson disease (PD). The FDA’s decision came following a five-month assessment after national reports implied 741 treated patients with PD died since June 2016.
Pimavanserin, along with other antipsychotics, carries a Boxed Warning for the increased risk of death in elderly patients with dementia-related psychosis. But the FDA had ruled that none of their investigation findings were inconsistent with the already-established safety profile detailed on the drug label.
As a selective serotonin inverse agonist which primarily targets the 5-HT2A receptors, pimavanserin primarily addresses receptors associated with the mechanisms of depression, psychosis, and other neuropsychiatric disorders. It is currently being evaluated for dementia-related psychosis, schizophrenia inadequate response, and schizophrenia-negative symptoms. It was approved for the treatment of hallucinations and delusions associated with PD psychosis by the FDA in April 2016.
As a potential MDD adjunctive therapy, the therapy could help address the approximate 16 million US adults with the condition, and 2.5 million already treated with adjunctive drugs.