On October 31, 2018, ACADIA Pharmaceuticals Inc. announced positivetop-line results from CLARITY, a randomized, double-blind, placebo-controlled multi-center, sequential parallel comparison design study in major depressive disorder (MDD). A copy of ACADIA’s press release announcing thetop-line results is attached as Exhibit 99.1.
Trial Design andTop-line Results
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 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 MGH Clinical Trials Network & Institute and randomized 207 patients across 28 clinical research centers in the United States.
Consistent with the SPCD design, CLARITY was conducted in two five-week sequential stages. Eligible subjects continued receiving their SSRI/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. Placebonon-responders in Stage 1 (defined asHAMD-17 total score >14 and a percent-reduction from baseline inHAMD-17 total score of <50% at week 5) werere-randomized (1:1) to receive pimavanserin 34 mg/day or placebo. The primary endpoint of the study was the change inHAMD-17 total score for Stage 1 and Stage 2. Treatment differences from Stage 1 and Stage 2 were combined as weighted averages.
In the trial, pimavanserin met the overall primary endpoint of the weighted average results of Stage 1 and Stage 2 by significantly reducing theHAMD-17 total score compared to placebo (p=0.039). In addition, in Stage 1 (n=207) patients on pimavanserin demonstrated a highly significant improvement inHAMD-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 placebonon-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 other secondary endpoints listed below with nominal p values: Clinical Global Impression-Severity (p=0.0084), Clinical Global Impression-Improvement (p=0.0289), ShortForm-12 Mental Component Summary (p<0.0001), Karolinska Sleepiness Scale (p=0.0205), Massachusetts General Hospital Sexual Functioning Index (p=0.0003), Barratt Impulsiveness Scale (p=0.0075), as well as response rates (p=0.0065), defined as a 50% or greater reduction on theHAMD-17 total scale.
Apost-hoc comparison between pimavanserin (n=51) and placebo (n=123) for patients consistently receiving either placebo or pimavanserin for the entire10-week period also yielded meaningful separation with positivep-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).
Safety and Tolerability
In CLARITY, 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.
| Item 9.01 | Financial Statements and Exhibits. |
| (d) | The following exhibit is furnished herewith: |
