An analyst on behalf of Joel Beatty asked for a general breakdown of the anticipated patient population for vatiquinone between pediatric (under 16) and adult patients.
CEO Dr. Matthew Klein reiterated the company's estimate that of the approximately 6,000 Friedreich's ataxia patients in the U.S., about one-third are in the pediatric population.
Joel Beatty followed up on the expected 'bolus of patients' for PKU, asking about the likely cadence of therapy initiation at launch and any potential rate-limiting factors.
CBO Eric Pauwels explained that the launch cadence will be managed by preparing teams to handle a high volume of physician start forms. He noted that experienced centers and proactive work to minimize step edits will be key. The primary rate-limiting factor will be aligning internal staffing and case management to handle the anticipated high initial demand.
Joel Beatty of Baird asked what portion of ex-U.S. Translarna sales would be unaffected by a negative EU decision and about the likelihood of an FDA Advisory Committee (AdCom) meeting for vatiquinone.
CEO Matthew Klein explained that approximately 46% of 2023 Translarna revenue came from Europe and would be at risk, while revenue from other regions, where exclusivity extends to 2029, would be unaffected. Regarding vatiquinone, he stated it is difficult to predict if an AdCom will be required but suggested it may not be, given the FDA's familiarity with Friedreich's ataxia.
Joel Beatty asked for an update on the timelines and strategy for the development of the auto-injector.
Chief Operating Officer Karen Massey confirmed that the team is consistently working on patient-centric innovations, including the auto-injector. She stated that the development plan is on track, with the latest update being the program's move into understanding how to produce it at a larger capacity, and that the company looks forward to bringing more innovation to patients in the future.
An analyst on behalf of Joel Beatty asked that if the prefilled syringe (PFS) is approved in April, how soon could it reach patients.
Chief Operating Officer Karen Massey confirmed that the company will be ready to launch 'as soon as after the PDUFA date.' She expects the product to be available to patients 'within days' of a potential approval.
Joel Beatty inquired about the sales trajectory of VYVGART throughout the seasonally challenging first quarter and into the beginning of the second quarter.
COO Karen Massey stated she was pleased with the Q1 growth despite seasonal headwinds, attributing it to strong underlying fundamentals like new patient growth and market share gains. She confirmed that this positive momentum was continuing into Q2 and expressed confidence for the remainder of the year.
Joel Beatty of Robert W. Baird & Co. asked about the safety profile of Avexitide, a GLP-1 antagonist, given the well-known effects of GLP-1 agonists, and what provides confidence it won't cause issues. He also asked a follow-up question about the company's current thinking on business development activities.
Co-CEO Justin Klee addressed the safety question by highlighting the favorable safety data from non-clinical and clinical studies to date. He explained that as a competitive antagonist, Avexitide attenuates endogenous GLP-1 rather than reversing its effects. Regarding business development, he stated that while the company's mission includes seeking promising external assets, the immediate focus is on executing its four current clinical trials.
Joel Beatty of Baird posed two questions regarding Amylyx's pipeline. He asked what specific outcomes the company is looking for in the upcoming week 48 data from the Wolfram syndrome trial to support regulatory discussions, and also inquired about the potential for developing avexitide in other indications beyond post-bariatric hypoglycemia (PBH).
Chief Medical Officer Dr. Camille Bedrosian responded that for the Wolfram trial, they hope to see sustained improvements in C-peptide response and stabilization or improvement in visual acuity, which would demonstrate continued beta-cell and retinal health. On expanding avexitide's use, Co-CEO Joshua Cohen stated that while PBH is the primary focus, they believe the GLP-1 antagonist mechanism has potential in other diseases characterized by hyperinsulinemic hypoglycemia.
Joel Beatty of Baird inquired about Catalyst's current perspective on business development amid a changing macro environment. He also asked for any early anecdotes that provide confidence in the strategy to increase FIRDAPSE use in cancer-associated LEMS through enhanced diagnosis.
President and CEO Richard Daly stated that the current market turmoil is beneficial for their disciplined M&A strategy, which focuses on near-commercial, accretive assets. Regarding the LEMS strategy, both Mr. Daly and CCO Jeffrey Del Carmen confirmed significant interest from oncology key opinion leaders in advisory boards, who recognize the unmet need and are receptive to frictionless VGCC antibody testing.
Joel Beatty inquired about the observed impact of generic EMFLAZA on the market and its potential effect on AGAMREE's growth. He also asked for quantification of the expected increase in SG&A expenses for 2025.
CCO Jeffrey Del Carmen stated that they have not seen significant generic conversion from branded EMFLAZA and do not expect it to impact AGAMREE's growth in 2025, noting payer policies have not changed. CEO Richard Daly added that patients have likely already tried other steroids, making a step-back to a generic unlikely. Regarding SG&A, executive Michael Kalb declined to quantify the 2025 increase, stating more clarity would be provided as the year progresses and hiring is completed.
An analyst on behalf of Joel Beatty of Baird posed a quantitative question about DAYBUE's patient dynamics, asking if the current patient base and persistency rate imply a high number of annual discontinuations that would be challenging to replace with new patient starts.
CEO Catherine Owen Adams and an executive, likely CFO Mark Schneyer, clarified the patient math. They explained that the >50% persistency figure applies to the first 12 months, after which the rate is very high. With 65% of current patients already on therapy for over a year, this creates a stable, growing base, meaning new patient additions contribute to net growth rather than just replacing discontinuations.
Joel Beatty questioned the basis for the increased estimate of diagnosed U.S. Rett syndrome patients and asked for a comparison of ACP-711's mechanism to SAGE-324 for essential tremor.
CEO Catherine Owen Adams attributed the higher patient estimate (now 5,800) to ongoing data analysis, which is common for a first-in-market rare disease drug. EVP of R&D Elizabeth Thompson differentiated ACP-711 by explaining its high selectivity for GABA alpha 3 containing receptors, which aims to target dysfunction in essential tremor more precisely and potentially spare side effects seen with less selective agents.
Joel Beatty of Baird questioned the ratio of Daybue patients to unique prescribers, noting that with ~1,500 patient starts and ~800 prescribers, the average of less than two patients per prescriber seems less concentrated than might be expected.
Executive Brendan Teehan acknowledged the long tail of prescribers. He explained that while Centers of Excellence and high-volume institutions have a concentration of physicians with multiple referrals, prescribing in the community setting is less concentrated. It is common to see community-based primary care physicians or pediatricians who may only have one or two Rett patients. The company is now focusing on encouraging physicians who have prescribed once or twice to identify additional patients under their care.
Joel Beatty from Baird asked about the expected initial placement of Dordaviprone in the treatment algorithm upon approval and the potential timing for the first results from the confirmatory ACTION trial.
Rob Iannone, Head of R&D, stated that based on the submission, the initial accelerated approval for Dordaviprone is expected in the recurrent disease setting. He confirmed the ongoing ACTION trial is evaluating its use in the frontline setting, which could support label expansion, but did not provide a specific timeline for the data readout, noting only that it is enrolling to plan.
Joel Beatty asked about the company's strategy to maintain VIVITROL revenue in 2027 and beyond, considering the potential for generic competition to enter the market.
CEO Richard Pops expressed confidence in VIVITROL's durability, citing its strong performance in alcohol dependence. He reiterated the belief that VIVITROL is a complex product to manufacture and commercialize, and therefore is not expected to follow a typical generic erosion curve. The company is prepared to drive demand or flex its commercial infrastructure to maintain profitability.
Joel Beatty asked about the key dynamics that would determine whether VIVITROL achieves its guided mid-single-digit prescription growth rate for 2025.
CCO C. Nichols responded that the primary driver is the continued expansion in the alcohol dependence indication, which grew approximately 14% in 2024. He added that as a mature brand, subnational dynamics, particularly within the VA system, will also be a key area of focus for growth.
Joel Beatty inquired about the remaining runway for LYBALVI commercial contracting and asked about future plans for the direct-to-consumer (DTC) advertising program, noting its spending appeared to be ramping down in Q4.
CCO Todd Nichols stated that while the access profile for LYBALVI is in a very good position, discussions with payers are ongoing, with any future deals contingent on driving profitable volume growth. He confirmed that DTC is a productive investment and will continue in 2025, with spending becoming more consistent quarter-to-quarter as the company focuses on the most productive channels.
Chris Chen, on for Joel Beatty, asked for an update on the potential timeline for the AXS-05 trial in smoking cessation in 2025 and whether the study would differentiate between users of traditional cigarettes and e-cigarettes.
Chief Executive Officer Dr. Herriot Tabuteau confirmed the company is confident the Phase III trial for smoking cessation will start this year and that more details on the study design will be shared soon. He clarified that the initial registration trial will focus on traditional cigarette smokers, with other forms of nicotine use to be considered at a later date.
Joel Beatty of Baird asked how much additional reach the new sales force expansion provides and when Axsome expects to be able to file an NDA for AXS-05 in Alzheimer's Disease Agitation.
An executive, likely CCO Ari Maizel, explained the expansion provides a dual benefit of increased reach and higher frequency with key prescribers. CEO Herriot Tabuteau outlined the ADA filing timeline, stating it generally takes 6-9 months to prepare an NDA after study completion and a pre-NDA meeting.
Joel Beatty asked if a successful interim for ulixacaltamide would lead to an immediate release of final results and whether relutrigine's efficacy is limited to patients already responsive to sodium channel blockers.
CEO Marcio Souza confirmed that if the high bar for efficacy is met at the interim, final results for ulixacaltamide would be released at the same time. He also explained that preclinical data suggests relutrigine's mechanism should provide a wide range of efficacy, not restricted to patients with a prior response to other sodium channel blockers.
Joel Beatty asked what the next update from the Essential3 program will be and whether the trial's data has been reviewed on a blinded basis to assess variability.
CEO Marcio Souza responded that the next updates will cover program milestones, including enrollment and the interim analysis. He confirmed that the data is continuously reviewed on a blinded basis and that variability is in line with expectations, stating that this was not the reason for implementing the planned interim analysis.