ACADIA Pharmaceuticals Spotlights Alzheimer’s Psychosis Pipeline, NUPLAZID and DAYBUE Growth

Key Points

• ACADIA is advancing remlifanserin for Alzheimer’s disease psychosis, emphasizing higher exposure levels and a trial design meant to reduce QTc concerns and improve efficacy signals seen with pimavanserin.
• NUPLAZID sales are getting a boost from a 30% expansion in the sales force, but management said the rollout is still early and the biggest impact should come in the back half of the year.
• DAYBUE growth is being supported by the new STIX formulation, which aims to improve convenience and persistence, while ACADIA also continues its European reexamination process for the drug.

ACADIA Pharmaceuticals NASDAQ: ACAD executives used an RBC Capital Markets investor session to outline the company’s clinical rationale for remlifanserin in Alzheimer’s disease psychosis, provide updates on commercial trends for NUPLAZID and DAYBUE, and discuss selected pipeline and business development priorities.

The discussion, hosted by RBC Capital Markets analyst Nevin Varghese, featured ACADIA executives including Sanjeev Pathak, senior vice president and head of clinical development, and Tom Garner, chief commercial officer.

Remlifanserin Program Focuses on Higher Exposure and Trial Design

Pathak said the key distinction between remlifanserin and pimavanserin is ACADIA’s effort to eliminate or mitigate QTc prolongation concerns. He said non-clinical data, in vitro studies and emerging clinical observations have supported that view, potentially allowing ACADIA to test higher doses and exposures.

“What it allows us to do is increase the dose, increase the exposures,” Pathak said. He added that ACADIA’s prior pimavanserin work suggested higher average blood levels were associated with stronger efficacy.

Pathak said the remlifanserin program includes two doses: 30 milligrams, which he described as equivalent to pimavanserin 34 milligrams or the NUPLAZID dose, and 60 milligrams, which is intended to provide higher exposure. He also noted that remlifanserin has a shorter half-life than pimavanserin, reaching steady state in roughly five to six days in elderly patients, compared with 12 to 15 days for pimavanserin.

In Alzheimer’s disease psychosis, Pathak said ACADIA is applying several lessons from its earlier pimavanserin experience. Those include running a dedicated program with multiple studies, enriching for patients with more severe psychosis, and using what the company considers a more sensitive endpoint, SAPS-H+D.

Asked about trial conduct and placebo response, Pathak said ACADIA is using experienced staff from the pimavanserin program, emphasizing site selection, investigator training, blinded monitoring and biomarker confirmation of Alzheimer’s disease. He said the company is seeking to reduce patient heterogeneity and exclude patients whose symptoms may resemble Alzheimer’s disease psychosis but arise from other psychiatric causes.

Pathak said the current study is powered at 80% for a moderate standardized effect size of 0.4. He said the goal is to generate data that can inform and enrich potential Phase 3 development. While acknowledging that effect sizes can shrink from Phase 2 to Phase 3, he said ACADIA hopes to use Phase 2 learnings to refine the Phase 3 population and biomarkers, depending on the data.

NUPLAZID Sales Force Expansion Still in Early Stages

Garner said ACADIA expanded its NUPLAZID sales team in the first quarter, increasing overall reach by about 30%. He said the company now covers roughly 10,000 customers, with neurologists representing about 45% of that group and remaining a primary focus.

Garner said ACADIA has seen a shift in the mix of NUPLAZID prescribers over the past two years, helped by direct-to-consumer and healthcare professional outreach. In the first quarter, he said about 25% of total writers were new-to-brand writers.

However, Garner cautioned that it remains early to judge the full impact of the sales force expansion. The expanded team was fully trained and in the field around the middle of the first quarter, and ACADIA expects a six- to nine-month ramp before the model reaches full efficiency. He said the company expects the impact to be more weighted toward the back half of the year.

Garner also addressed refill delays seen in the first quarter, saying the company did not identify a specific underlying issue. He attributed the disruption to a larger-than-usual group of patients returning late, noting that NUPLAZID has high Medicare exposure, with roughly 80% of patients on Medicare. He said the company does not expect the issue to create a continuing drag through the rest of the year.

DAYBUE STIX Launch Aims to Support Persistence and Reengagement

Garner said ACADIA’s DAYBUE strategy has expanded beyond Rett syndrome Centers of Excellence into community settings. He said about two-thirds of Rett patients fall outside direct care at a Center of Excellence, and ACADIA remains under-penetrated in that segment, in the late-20% range.

On persistence, Garner said ACADIA is seeing a growing base of patients remaining on therapy as more cohorts move through 12 and 18 months. He said 12-month persistence across cohorts is north of 50%, close to 55%, while 18-month persistence is in the 50% range.

Garner said the launch of DAYBUE STIX in the first quarter could help support additional growth and longer treatment duration. The product is a powder formulation that can be mixed with non-dairy liquids, requires no refrigeration and is more portable than the liquid formulation. He said ACADIA has removed many excipients that had been a concern for some patients and caregivers.

Initial demand has come from treatment-naive patients, returning patients and patients considering a switch from liquid DAYBUE, Garner said. He added that feedback from caregivers and healthcare professionals has been positive, particularly because the formulation responds to concerns raised about the liquid product.

Garner said ACADIA amplified its direct-to-consumer efforts in April after the initial Centers of Excellence-focused launch. He said the company’s Family Support Educators have also been reengaging families, including those who discontinued therapy because of formulation concerns.

European Review and Pipeline Updates

Pathak said the reexamination process for DAYBUE in the European Union is structured and time-bound, with ACADIA expecting it to conclude by the end of June. He said rapporteurs have been assigned, the company has submitted its grounds for reexamination and ACADIA is preparing for both a Scientific Advisory Group meeting and an oral reexamination.

Pathak also discussed ACP-271, ACADIA’s GPR88 agonist, saying the company is excited by the program’s potential in movement disorders and associated neuropsychiatric symptoms. He said GPR88 is abundant in motor areas of the brain and present at lower density in areas tied to higher cognitive function. ACADIA has seen consistent non-clinical benefit in animal models, including tardive dyskinesia models, without typical safety findings such as sedation, according to Pathak.

On business development, a company representative said ACADIA continues to take a “barbell” approach, looking at both neuroscience and rare disease opportunities. The company is interested in late-stage assets that could launch within the next several years, as well as earlier-stage assets that could supplement its early-stage portfolio.

About ACADIA Pharmaceuticals NASDAQ: ACAD

ACADIA Pharmaceuticals Inc is a biopharmaceutical company focused on the development and commercialization of innovative therapies for central nervous system (CNS) disorders. Established in 1993 and headquartered in San Diego, California, ACADIA's research centers concentrate on conditions with significant unmet medical needs, including Parkinson's disease psychosis, Alzheimer's disease psychosis, and schizophrenia. The company utilizes a range of scientific platforms, including selective receptor modulation and precision-targeted compounds, to advance its portfolio of small-molecule therapeutics.

The company's flagship product, NUPLAZID® (pimavanserin), received U.S.

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