Executives from Axsome Therapeutics (NASDAQ:AXSM) outlined the company’s recent commercial momentum and upcoming clinical and regulatory milestones during a fireside chat at Oppenheimer’s annual healthcare conference, highlighting continued uptake for Auvelity in major depressive disorder (MDD), preparations for a potential new indication in Alzheimer’s disease agitation (ADA), and progress across its broader central nervous system (CNS) portfolio.
Auvelity in MDD: uptake, access, and sales force expansion
Management attributed Auvelity’s recent performance in MDD to continued demand across patient types, improved market access, and commercial execution. The company described an adoption cycle in which “trialists become adopters” and “adopters become advocates,” supported by coverage improvements and prior field force additions.
Coverage metrics and gross-to-net expectations
On reimbursement, executives provided updated coverage figures and discussed gross-to-net (GTN) dynamics. They said Auvelity has approximately 86% total covered lives, including 78% commercial covered lives and 100% coverage in the government channel. For the fourth quarter, they said GTN was in the high-40% range for Auvelity.
Looking ahead, the company said it views 2025 as a “good proxy” for what 2026 could look like from a GTN perspective, while noting seasonality. Management also referenced that GTN was in the mid-50% range in the first quarter and said it would expect a similar seasonal pattern.
Executives added that more than half of total Auvelity prescriptions are now in first-line or first-switch use. They broke that down further by saying first-line use is around (or above) 15%, with roughly 35% (or just under) in first switch, which they characterized as a meaningful evolution from early launch dynamics when Auvelity was used more often in later-line patients.
Persistence commentary
When asked about patient persistence on Auvelity, the company said it has not yet disclosed a specific retention metric because it is still monitoring persistence as prescribing shifts across patient profiles and lines of therapy. Axsome said persistence is currently tracking in line with what is typically seen for antidepressants, and management described a range of possible drivers, including rapid remission and patient decisions about staying on medication to maintain remission versus discontinuing to reduce medication burden.
Executives said they are seeing growth from both new-to-brand prescriptions (NBRx) and total prescriptions (TRx) and indicated they may provide a more precise persistence figure once they have greater confidence in the data.
Alzheimer’s disease agitation: market, data package, and launch preparation
A major focus of the discussion was Axsome’s supplemental NDA for Auvelity in Alzheimer’s disease agitation, which is under FDA priority review with a PDUFA date of April 30. The company reviewed how agitation is assessed in trials using the Cohen-Mansfield Agitation Inventory (CMAI), noting it covers behaviors such as physical and verbal aggression as well as non-verbal behaviors like restlessness.
Management said the market has historically been dominated by off-label use of generics—including atypical antipsychotics and antidepressants—due in part to limited innovation and measurement challenges. Executives estimated there are about seven million Alzheimer’s patients and said roughly 70% experience forms of agitation, which they described as about five million patients, with approximately 20 million prescriptions written annually—most of them off-label.
On the regulatory submission, the company said FDA requested a new, standalone ICH safety database given the elderly patient population, despite Auvelity already being approved in another indication. Axsome said its ADA clinical package included:
- Four controlled trials, with three positive studies (ADVANCE-1, ACCORD-1, and ACCORD-2) and one additional controlled study (ADVANCE-2) included as part of the totality of evidence
- A long-term safety study designed to provide the ICH exposures needed
- Two trial paradigms, including parallel-group longitudinal trials and randomized withdrawal studies, which management said provide information on longitudinal change and durability of response
Executives said the program demonstrated statistically significant separation at week three in ADVANCE-1 and described responses as “very durable” in the ACCORD trials and long-term safety experience. On safety, management said it did not observe a signal for falls or mortality and characterized the overall tolerability profile as favorable in the elderly population. The company also emphasized that Auvelity’s mechanism is different from both on-label and commonly used off-label options in this setting.
Commercial strategy for ADA and broader pipeline updates
In terms of launch preparation, Axsome said it has initiated a non-branded awareness campaign and website focused on Alzheimer’s disease agitation, alongside medical affairs outreach and education efforts through its MSL team.
Management emphasized that ADA is expected to be predominantly a Medicare Part D opportunity, estimating that more than 70% of ADA prescriptions will be in Part D. The company highlighted that it already has 100% coverage in the government channel, which it described as an advantage relative to the MDD launch when covered lives were an initial hurdle. Axsome also said it expects GTN per ADA script to be better than GTN per MDD script, noting Medicare Part D dynamics and the absence of co-pay coverage, and suggested that as ADA grows to represent a larger portion of Auvelity volume, blended GTN for Auvelity could improve.
Elsewhere in the portfolio, management provided brief timing and regulatory expectations for solriamfetol expansion programs. For binge eating disorder (BED), the company said its first phase 3 study is ongoing with topline data expected in the second half of the year, and that its last alignment with FDA indicated two trials would likely be needed. For shift work disorder, it said topline data are expected next year and that FDA alignment supports a single study for a potential label expansion if the trial is positive.
The company also noted it recently dosed the first patient in a solriamfetol study in MDD using a precision approach focused on patients with symptoms of excessive daytime sleepiness, adding that it has not provided timing guidance yet given the early stage of enrollment and expects two studies for that package.
On AXS-12, management said the NDA submission is imminent and described strong commercial synergy with the existing sleep-focused sales force supporting Sunosi, calling it “plug and play” if approved. For AXS-17, which the company recently in-licensed in epilepsy, executives said the asset was acquired on what they viewed as compelling economic terms and that the program fits Axsome’s R&D and commercial infrastructure. They said the company has not confirmed the target indication yet and expects 2026 to focus on phase 2 enabling work.
Closing on financial strategy, management said the expanded field force represents an acceleration of commercial investment while maintaining operating leverage and that the move does not change guidance. Executives said the company has “near-term sight for cash flow positivity,” noting it has recently been close to cash flow positive on a cash basis from a net loss perspective, and said it continues to see a near-term path toward EPS positivity.
About Axsome Therapeutics (NASDAQ:AXSM)
Axsome Therapeutics, Inc is a clinical-stage biopharmaceutical company dedicated to developing novel therapies for central nervous system (CNS) disorders. The company focuses on small-molecule drugs designed to address unmet medical needs in areas such as depression, migraine, narcolepsy and fibromyalgia. Axsome employs a precision medicine approach, leveraging pharmacologic innovation to target underlying mechanisms of disease and improve patient outcomes.
Axsome’s pipeline includes several late-stage and approved product candidates.
