Dr Gus AlvaGus Alva, MD
New phase 2 results suggest that investigational pimavanserin treatment, as monotherapy or adjunct to selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI) therapy, is associated with an improvement in patients with Parkinson disease who have depressive symptoms.1

The 8-week, open-label study included 47 patients with Parkinson who were treated with Acadia Pharmaceuticals’ selective serotonin inverse agonist and 5-HT2A targeting antagonist, who ultimately reported significant improvements in Hamilton Depression Rating Scale (HAMD-17) scores (P <.0001). Notably, this improvement was seen as early as the second week of treatment (P <.0001).

The data were presented at the 2019 International Congress of Parkinson’s Disease and Movement Disorders, in Nice, France.

“Mood disorders, particularly depression, occur in approximately 50% of patients with PD, and depressive symptoms in patients with PD are associated with diminished quality of life, greater disability, and faster progression of physical symptoms,” study author Gus Alva, MD, founder and medical director, ATP Clinical Research, said in a statement. “Results of this open-label study suggest that pimavanserin may be a potential treatment to be further investigated for depression associated with Parkinson’s disease.”

At week 8, 60% of the cohort had experienced a ≥50% improvement in HAMD-17 score. As well, 44.4% of patients reached remission, defined as HAMD-17 score ≤7.

Among the secondary end points assessed, a number showed statistically significant improvements for patients given pimavanserin. Clinical Global Impression-Severity scale improvements from baseline to week 8 were significant (P <.0001), and Clinical Global Impression-Improvement scores were lowered from 2.5 at week 2, to 2.0 at week 8.

Scales for Outcomes in Parkinson Disease (SCOPA)-night-time sleep and SCOPA-day-time sleep scales reported improvements across all 3 measures at the halfway point of the study and continuing through to study’s end. The SCOPA-Global Sleep Quality scale improved significantly over the course of the study as well (P <.0001).

“We are pleased with the exploratory study results which show a positive treatment effect with pimavanserin for depression in patients with Parkinson’s disease,” said Serge Stankovic, MD, MSPH, president, ACADIA, in a statement. “These results are also consistent to those observed in our Phase 2 study with pimavanserin as an adjunctive treatment for patients with an inadequate response to existing first-line SSRI/SNRI therapy for major depressive disorder.”

With regard to safety,  pimavanserin was determined to be well-tolerated. Adverse events (AEs) were consistent with prior studies of patients treated with pimavanserin, and the most common included falls (8.5%), nausea (6.4%), diarrhea (4.3%), edema (4.3%), skin abrasion (4.3%), and urinary tract infection (4%).

“We are committed to continued research for pimavanserin to address unmet medical needs in central nervous system disorders, including our ongoing Phase 3 clinical program in major depressive disorder,” Stankovic said.

Pimavanserin (Nuplazid) is an FDA-approved treatment of Parkinson disease-related psychosis. It was recently involved in a phase 3 trial, HARMONY, which was halted after the treatment demonstrated a highly statistically significant reduction in relapse in patients with dementia-related psychosis.

The selective serotonin inverse agonist and antagonist preferentially targeting 5HT2A receptors is also under investigation for major depressive disorder and schizophrenia. In July 2019, Acadia reported disappointing late-stage results in that population, noting that pimavanserin failed to improve psychosis symptoms versus placebo in adults with schizophrenia who have an inadequate response to their current antipsychotic therapy.2

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REFERENCES
1. ACADIA Pharmaceuticals Presents New Data on PD Patients Treated with Pimavanserin for Depression at the 2019 International Congress of Parkinson’s Disease and Movement Disorders [press release]. San Diego, CA: Acadia Pharmaceuticals; Published September 23, 2019. finance.yahoo.com/news/acadia-pharmaceuticals-presents-data-pd-130000578.html. Accessed September 24, 2019.
2. Acadia Pharmaceuticals Announces Pivotal Phase 3 HARMONY Trial Stopped Early for Positive Efficacy as Pimavanserin Meets the Primary Endpoint in Patients with Dementia-Related Psychosis [news release]. San Diego, CA: Acadia Pharmaceuticals Inc. September 9, 2019. biospace.com/article/releases/acadia-pharmaceuticals-announces-pivotal-phase-3-harmony-trial-stopped-early-for-positive-efficacy-as-pimavanserin-meets-the-primary-endpoint-in-patients-with-dementia-related-psychosis. Accessed September 24, 2019.