What would 'good' remlifanserin ADP data look like, specifically regarding the SAPS-HD primary endpoint at week 6, powering, and the exploratory NPIC endpoint?

Liz Thompson stated they are looking for continued evidence of a molecule aligned with their target product profile (easy to take, good safety, no negative impact on motor/cognition). The study is powered for a moderate effect size of 0.4 on SAPS-HD at week 6, and statistical significance would be positive. NPIC is an exploratory endpoint and not powered for. “In particular, around powering and the SAPS-HD, from a primary endpoint perspective, what we have powered for here is a moderate effect size, so 0.4 in particular. We'll be pleased, of course, if we see statistical significance on that at week 6.”

Update on DAYBUE patient persistency and compliance trends.

Tom Garner confirmed that persistency and discontinuation rates remain consistent with previous quarters, with discontinuations in the low single-digit range and consumption in the high 60% range for the full year. He emphasized that the business has stabilized and is now back on a growth trajectory, with STIX expected to drive the next wave of growth. “Our discontinuations remain in the pretty low single-digit range. They've really stabilized. Consumption kind of remains as we've shared before, which I think for the full year was kind of the high 60% range.”

What is the timeline for the upcoming remlifanserin ADP Phase III trial, and what are the specific concerns regarding the EU opinion for DAYBUE and how will they be addressed in reexamination?

Liz Thompson explained that the remlifanserin Phase II and Phase III are operationally seamless, meaning Phase III enrollment can begin as soon as Phase II enrollment stops later this year. Regarding the EU, while the final opinion is not yet received, anticipated concerns include endpoint relevance, clinical meaningfulness, duration of therapy, and mechanism of action. She noted that 20-30% of reexaminations result in a positive opinion, and they will address specific grounds for refusal. “So we look to move from Phase II to Phase III enrollment later in the course of this year.”

ACAD

ACADIA (ACAD) Q4 FY25 earnings call: guidance and Q&A

Earnings call· Dec 2025 (Q4 FY25)· Health Care· Feb 25, 2026

Source: earnings call transcript

Executive summary

ACADIA Q4 FY25 — Strong Commercial Performance and Pipeline Progress

ACADIA Pharmaceuticals closed FY25 with strong commercial execution for both NUPLAZID and DAYBUE, exceeding $1 billion in annual adjusted revenues for the first time. The company is making foundational SG&A investments to support continued growth towards 2028 targets, while navigating higher-than-anticipated IRA rebates and a negative EU regulatory trend vote for DAYBUE. The R&D pipeline is advancing, with a key Phase II readout for remlifanserin expected later in 2026.

Highlights

Achieved adjusted total revenues of $298 million in Q4 FY25, up 16% from the prior year, with annual revenues exceeding $1.08 billion for FY25.
NUPLAZID delivered adjusted net sales of $189 million in Q4 FY25, growing 17% year-over-year, driven by 13% volume growth and 18% increase in new prescriptions.
DAYBUE net sales reached $110 million in Q4 FY25, up 13% year-over-year, with 1,070 patients receiving shipments globally and 76% of new prescriptions from community physicians.
Launched DAYBUE STIX, a new powder formulation, approved by the FDA in December, expected to unlock over 400 incremental patients over the next 2-3 years.
Advanced a robust R&D pipeline with a key Phase II readout for remlifanserin in Alzheimer's disease psychosis expected August-October 2026, targeting a $4 billion peak sales potential.

Concerns

Received higher than anticipated Inflation Reduction Act (IRA) invoices from CMS for NUPLAZID, resulting in a nonrecurring $20 million reduction in net sales due to an accounting change in estimate.
Received a negative trend vote from the CHMP for the trofinetide marketing application in the EU, with a negative final opinion anticipated, leading to a reexamination process.
2026 DAYBUE guidance of $460 million to $490 million does not include potential EU commercial sales due to the uncertain regulatory status.

Guidance & targets

Category	Target	Timeline	Confidence
NUPLAZID Net Sales	$760 million to $790 million high materiality	FY26	High
NUPLAZID Net Sales (Midpoint)	$775 million high materiality	FY26	High
NUPLAZID Net Sales	$1 billion high materiality	FY28	High
DAYBUE Global Net Sales	$460 million to $490 million high materiality	FY26	High
DAYBUE Global Net Sales	$700 million high materiality	FY28	High
Total Revenues	$1.22 billion to $1.28 billion high materiality	FY26	High
NUPLAZID Gross to Net	22% to 24% medium materiality	FY26	High
DAYBUE Gross to Net	22% to 24% medium materiality	FY26	High
R&D Expense	$385 million to $410 million medium materiality	FY26	High
SG&A Expense	$660 million to $700 million medium materiality	FY26	High
Operating Margin (no attrition)	mid-teens medium materiality	FY28	Medium
Operating Margin (normal attrition)	low 20% medium materiality	FY28	Medium

Segment performance

Segment	Revenue	YoY	QoQ	Margin
NUPLAZID Adjusted net sales. Growth was broad-based across all channels, reflecting continued traction and effectiveness of commercial strategy. Volume Growth Q4: 13%Volume Growth FY25: 9%New Prescriptions Growth Q4 YoY: 18%New Prescribers FY25: 40% new to brand	$189M	17%	—	—
DAYBUE Net sales. Driven by strong U.S. performance and growing contributions from rest of world programs. Core business fundamentals remain strong with low discontinuation rates. Volume Growth Q4: 12%Patients Receiving Shipments Q4: 1,070 globallyNew Prescriptions from Community Physicians Q4: 76%	$110M	13%	—	—

Product announcements

Product	Type	Timeline	Details
DAYBUE STIX	launch	FDA approval December 2025; broader commercial launch early Q2 2026
DAYBUE liquid	expansion	Recent approval

Risks & headwinds

Higher-than-anticipated Inflation Reduction Act (IRA) invoices from CMS for NUPLAZID Q4 FY25 (impact), first 2 years of program (payment)

Nonrecurring $20 million reduction in net sales due to accounting change in estimate. $108 million payment for first 2 years of program.

Mitigation:Adjusted net sales methodology apportions the change in estimate to applicable years. Company will continue to monitor Medicare volume mix.

Negative trend vote from CHMP for trofinetide marketing application in EU Final opinion expected this week; reexamination process approximately 120 days, new final opinion around end of Q2.

Anticipated negative final opinion from CHMP. EU sales represent less than 15% of DAYBUE's projected $700 million 2028 sales.

Mitigation:Company plans to request a reexamination. Named patient supply programs remain active in the EU. EU sales are a small portion of long-term DAYBUE sales target.

Potential for placebo effect in clinical trials Ongoing for clinical trials

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Mitigation:Good training of investigators, looking for outliers, commitment to good clinical practice.

What to watch in Q1 FY26

DAYBUE STIX Commercial Launch Progress

Early Q2 2026

Current Early response very encouraging, initial product in channel, first patients receiving shipments.

Target Broader commercial launch in early Q2, continued positive patient mix and uptake.

Why it matters

Successful launch of DAYBUE STIX is a key driver for DAYBUE's 2026 growth and unlocking incremental patient opportunity.

Early patient mix is tracking in line with our expectations, and we remain on track for a broader commercial launch in early Q2 as we ensure appropriate inventory levels and a smooth transition for patients.

Find out whether ACAD delivers this. Inve re-checks your case every morning.

Q&A highlights

How should investors think about the ramp from 2026 guidance to the 2028 targets for both brands, and what gives management confidence?

Catherine explained that NUPLAZID's midpoint 2026 guidance implies low to mid-teens growth to reach $1 billion by 2028, while DAYBUE's midpoint implies low 20% growth to reach $700 million by 2028. Tom added that NUPLAZID's Q4 acceleration and expanded field force (30% increase, 6-9 month ramp) support continued demand, targeting 11,000 prescribers. DAYBUE STIX is expected to unlock additional growth, with early positive feedback.

“So if we take NUPLAZID and we look at our midpoint guidance for '26 at $775 million, that's about 12% above this year's growth on the adjusted basis. And so would indicate we're expecting low to mid-teens growth out to the $1 billion.”

asked by Tessa Romero · answered by Catherine Owen Adams

2 min read 5 chapters

Detailed narrative

Commercial Momentum and Strategic Investments

ACADIA reported strong Q4 and FY25 results, with adjusted total revenues exceeding $1 billion for the first time. Both NUPLAZID and DAYBUE demonstrated robust growth, driven by commercial execution and strategic investments. The company expanded its customer-facing teams by 30% for NUPLAZID and made significant marketing investments for both brands, expecting a 6-9 month ramp for the full impact of these investments.

This expansion aims to capitalize on underlying demand and penetrate the market further.

DAYBUE STIX Launch and Global Expansion

The FDA approval and early launch of DAYBUE STIX, a new powder formulation, is generating significant interest and is expected to unlock an incremental opportunity of over 400 patients over the next 2-3 years. This new formulation offers flexibility and portability, addressing caregiver feedback.

Globally, DAYBUE liquid is now approved in three markets, including Israel, and named patient supply programs continue to expand access outside the U.S., contributing to continued growth.

R&D Pipeline Progress and Key Catalysts

ACADIA's R&D pipeline is advancing with multiple programs, targeting large addressable markets with a combined peak sales potential of $11 billion. Key upcoming milestones include the Phase II readout of remlifanserin in Alzheimer's disease psychosis (ADP) between August and October 2026, and the initiation of a first-in-human study for ACP-271.

The company anticipates initiating 5 additional Phase II or Phase III studies and delivering 4 readouts by the end of 2027, highlighting the breadth and depth of its development portfolio.

Regulatory Headwinds for DAYBUE in EU

The company received a negative trend vote from the CHMP for its trofinetide marketing application in the EU and anticipates a negative final opinion. ACADIA plans to request a reexamination, a process expected to take approximately 120 days, with a new final CHMP opinion around the end of Q2.

Despite this, named patient supply programs in the EU remain active, ensuring patients maintain access to treatment during the regulatory process.

Financial Performance and IRA Impact

ACADIA reported adjusted total revenues of $298 million in Q4, up 16% YoY, and $1.08 billion for FY25, up 14% YoY. The company recorded a nonrecurring $20 million reduction in NUPLAZID net sales due to higher-than-anticipated Inflation Reduction Act (IRA) invoices from CMS, requiring an accounting change in estimate.

A one-time noncash income tax benefit of $250 million was recognized in Q4, strengthening the balance sheet.

Summary of the company's earnings call; see how call summaries are prepared. Not investment advice.