ACADIA Pharmaceuticals Announces Positive Top-line Results from Phase 2 CLARITY Trial of Pimavanserin for Adjunctive Treatment in Patients with Major Depressive Disorder (MDD)
- Pimavanserin met primary endpoint with statistically significant overall improvement in HAMD-17 total score compared to placebo (p=0.039)
- Pimavanserin met key secondary endpoint with statistically significant overall improvement in Sheehan Disability Scale compared to placebo (p=0.004)
- Positive results also observed on seven additional secondary endpoints including responder rate, improvement in sexual function, and reduction in daytime sleepiness
- ACADIA to initiate Phase 3 program in adjunctive MDD in 1H 2019
- Conference call and webcast to be held today at
In the trial, pimavanserin met the overall primary endpoint of the weighted average results of Stage 1 and Stage 2 by significantly reducing 17-item Hamilton Depression Rating Scale (HAMD-17) total score compared to placebo (p=0.039). In addition, in Stage 1 (n=207) patients on pimavanserin demonstrated a highly significant improvement in HAMD-17 (p=0.0003). Importantly, this group of patients saw a benefit over placebo in the first week of treatment (p=0.0365). Stage 2 (n=58) results did not demonstrate significant separation in this small set of placebo non-responders.
On the key secondary endpoint, pimavanserin demonstrated statistically significant reductions compared to placebo in the Sheehan Disability Scale (SDS) score (p=0.004).
Positive results were also observed for seven of the eleven other
secondary endpoints listed below with nominal p-values: Clinical Global
Impression-Severity (p=0.0084), Clinical Global Impression-Improvement
(p=0.0289), Short Form-12 Mental Component Summary (p<0.0001),
Karolinska Sleepiness Scale (p=0.0205),
In this Phase 2 study, pimavanserin was generally well-tolerated. Discontinuations due to adverse events were 1.2% for pimavanserin and 3.2% for placebo. One subject in each of the pimavanserin and placebo groups reported serious adverse events (SAEs). These SAEs were deemed not to be related to the study drug by the investigators and both subjects completed the study. No deaths were reported in the study.
“We are pleased with the robustness of the data from our Phase 2 CLARITY
trial, which shows significant promise for patients with MDD, including
early and sustained antidepressant response over placebo, decreased
daytime sleepiness, no meaningful weight gain, and improved sexual
function. This is important because most people with MDD do not respond
to initial antidepressant therapies and experience significant unwanted
side effects,” said
“The results of this study suggest pimavanserin may represent a novel
approach to adjunctive treatment for patients suffering from major
depressive disorder. The selective serotonergic mechanism of action may
provide additional benefit for patients who do not adequately respond to
SSRI or SNRI treatment,” said Professor
CLARITY was a Phase 2, 10-week, randomized, double-blind, placebo-controlled, multi-center, 2-stage sequential parallel comparison design (SPCD) study that evaluated the safety, tolerability, and efficacy of pimavanserin (34 mg once daily) as an adjunctive treatment in patients with MDD who had an inadequate response to a stable dose of standard antidepressant therapy with either a selective serotonin reuptake inhibitor (SSRI) or a serotonin norepinephrine reuptake inhibitor (SNRI). The study was conducted in collaboration with the
Consistent with the SPCD design, the study was conducted in two, five-week sequential stages. Eligible subjects continued receiving their SSRI or SNRI antidepressant at a stable dose for the duration of the study. Patients were randomly assigned (1:3) to pimavanserin 34 mg/day or placebo in Stage 1. Placebo non-responders in Stage 1 (defined as HAMD-17 total score >14 and a percent-reduction from baseline in HAMD-17 total score of <50% at week 5) were re-randomized (1:1) to Stage 2 to receive pimavanserin 34 mg/day or placebo. The primary endpoint of the study was the change in HAMD-17 total score for Stage 1 and Stage 2. Treatment differences from Stage 1 and Stage 2 were combined as weighted averages.
A post-hoc comparison between pimavanserin (n=51) and placebo (n=123) for patients consistently receiving either placebo or pimavanserin for the entire 10-week period also yielded meaningful separation with positive p-values at all weeks starting from week 2 to week 10 in favor of pimavanserin for both the primary endpoint, HAMD-17 (week 10, p=0.0076), and the key secondary endpoint, SDS (week 10, p=0.0094).
Conference Call and Webcast Information
ACADIA will discuss top-line results from its Phase 2 trial of pimavanserin for adjunctive treatment of patients with major depressive disorder via conference call and webcast today at
About Major Depressive Disorder (MDD)
According to the
Pimavanserin is a selective serotonin inverse agonist (SSIA) preferentially targeting 5-HT2A receptors. These receptors are thought to play an important role in depression, psychosis, and other neuropsychiatric disorders. ACADIA is evaluating pimavanserin in an extensive clinical development program across multiple indications with significant unmet need including dementia-related psychosis, schizophrenia inadequate response, schizophrenia-negative symptoms, and major depressive disorder. Pimavanserin (34 mg) was approved for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis by the
ACADIA is a biopharmaceutical company focused on the development and commercialization of innovative medicines to address unmet medical needs in central nervous system disorders. ACADIA has developed and is commercializing the first and only medicine approved for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. In addition, ACADIA has ongoing clinical development efforts in additional areas with significant unmet need, including dementia-related psychosis, schizophrenia inadequate response, schizophrenia-negative symptoms, major depressive disorder, and Rett syndrome. This press release and further information about ACADIA can be found at: www.acadia-pharm.com.
Statements in this press release that are not strictly historical in nature are forward-looking statements. These statements include, but are not limited to, statements related to: the potential benefits of pimavanserin as adjunctive treatment for MDD or other central nervous system disorders as well as the potential results of clinical trials of pimavanserin in other indications. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks and uncertainties inherent in drug discovery, development, approval and commercialization, and the fact that past results of clinical trials may not be indicative of future trial results. For a discussion of these and other factors, please refer to ACADIA’s annual report on Form 10-K for the year ended
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