San Diego-based ACADIA Pharmaceuticals reported topline data from its Phase III CLARITY study of Nuplazid (pimavanserin) as an adjunctive treatment for major depressive disorder (MDD). The study actually combined data from two identical studies. However, the study failed to hit statistical significance on the primary endpoint, which was the 17-item Hamilton Depression Rating Scale (HAMD-17) total score change from baseline to week 5.
In the trial of 209 patients, patients receiving 34 mg of Nuplazid once a day with standard antidepressant therapy demonstrated a mean reduction of 9.0 in HAMD-17 total score compared to 8.1 for placebo as an adjunctive treatment.
The trial did hit a key secondary endpoint, the Clinical Global Impression – Severity (CGI-S) score, which is a clinician evaluation of a patient’s severity of depression.
“We observed a consistent improvement of depressive symptoms over time with pimavanserin but, unfortunately, the robust positive results from our CLARITY-1 study were not replicated,” said Serge Stankovic, president of Acadia. “While these results do not support the product profile to pursue an additional Phase III study in adjunctive MDD, we will continue to analyze the data and the findings from our earlier positive depression studies as we assess next steps. All of us at Acadia thank the patients, their families and the investigators who participated in the Phase III CLARITY study.”
CLARITY is a combination of CLARITY-2 and CLARITY-3. Both were 6-week, parallel-designed, randomized, double-blind, placebo-controlled, multi-center studies. It was in patients with MDD who do not have an adequate response to standard antidepressant therapy with either a selective serotonin reuptake inhibitor (SSRI) or a serotonin norepinephrine reuptake inhibitor (SNRI).
Clinical trials of depression are typically difficult to successfully run and generally require several attempts to reach positive results. Acadia, however, has suggested it has no immediate plans to run another depression trial.
The U.S. Food and Drug Administration (FDA) is currently evaluating Nuplazid as a treatment for hallucinations and delusions linked to dementia-related psychosis. It has a target action date of April 3, 2021. This was announced today. Currently the FDA does not believe their review will require an Advisory Committee meeting.
“We are pleased that the FDA has accepted our sNDA for filing and we will be working closely with the FDA to facilitate completion of the review in a timely manner,” said Steve Davis, Acadia’s chief executive officer. “If approved, Nuplazid would be the first therapy indicated for the treatment of hallucinations and delusions associated with dementia-related psychosis. We look forward to potentially bringing this important treatment advancement to patients, caregivers and physicians.”
Nuplazid is approved for hallucinations and psychotic symptoms associated with Parkinson’s disease. The drug brought in $339 million in 2019 and is projected to hit $437 million this year.
Nuplazid is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors. The serotonin system is believed to have an important role in neuropsychiatric disorders. It was approved by the FDA in 2016 for hallucinations and delusions associated with Parkinson’s disease psychosis. It is not approved for dementia-related psychosis yet. The company is also developing the drug for other neuropsychiatric conditions.