Alkermes (NASDAQ:ALKS) CEO Richard Pops said the company is entering what he described as a “really exciting year” as the orexin agonist field moves closer to commercialization in narcolepsy, with broader ambitions in other disorders linked to wakefulness circuitry. Speaking in a conference panel discussion, Pops characterized sentiment inside Alkermes as “incredibly positive,” pointing to growing confidence in the company’s orexin program and the expanding scope of its development plans.
Expectations for the orexin agonist market and Takeda’s role
Pops said he expects Takeda’s orexin agonist to be approved “this year,” and argued that a first approval would have two major market effects: setting an initial price point for the class and revealing an early launch trajectory that could help define the commercial opportunity for subsequent entrants. Pops suggested Alkermes intends to compete on “more features and more benefits and more offerings for patients,” emphasizing the company’s view that it can “make good on the promise of the pharmacology.”
What Alkermes said it learned from the NT2 program
Pops pushed back on what he called “the tyranny” of viewing efficacy only through the Maintenance of Wakefulness Test (MWT), noting that in Alkermes’ NT2 study more than 70% of patients at the highest dose reported “normalcy” on the Epworth Sleepiness Scale (ESS), which he described as widely used clinically. He said the NT2 dataset showed substantial heterogeneity, including patients who did not respond on MWT but did respond on ESS.
As a result, Pops argued that mean group differences can obscure patient-level reality in NT2, where responders and non-responders can average out in a way that does not represent any particular patient. He said this variability is part of why Alkermes believes additional domains—such as fatigue and cognition—may become increasingly important in capturing the full patient experience.
Pops also addressed what investors often frame as tachyphylaxis or attenuation. He said Alkermes observed what it hypothesized to be a shift in “threshold concentration over time,” rather than a pharmacokinetic change, in NT2 patients who may have both endogenous and exogenous orexin. According to Pops, MWT signal degradation was seen by week four compared with day-one testing, but then appeared to stabilize rather than continuously decline. He said available data extending out to weeks six and eight, along with Takeda’s disclosures and ongoing long-term extensions, show “no evidence of further degradation” beyond that early reset.
Dosing flexibility and pivotal strategy
Pops said Alkermes accelerated its plans to incorporate split dosing into the pivotal program after learning that later time points in NT2 were “coming down faster,” and after hearing from some NT1 patients that they wanted wakefulness that extended longer into the day. He said Alkermes expects to launch with:
- A range of once-daily doses for NT1 and NT2
- A range of split-dose options to better match physiology and patient lifestyle “optionality”
He also said Alkermes has unique modeling capability based on matched pharmacokinetic sampling and MWT measurements taken every two hours during the NT2 phase II study, which included about 90 patients. Pops said this dataset supports modeling of split-dose regimens to address variability and optimize time above an efficacy threshold.
To generate a quantitative demonstration of split dosing, Pops said Alkermes added a split-dose arm to its ongoing IH study, with the goal of producing supporting data “this year” as the company also initiates phase III.
IH, SLEEP meeting plans, and view of endpoints
On IH, Pops said Alkermes saw similar responses between small cohorts of IH and NT2 patients in its phase 1b work, and emphasized that differential diagnosis can be fluid between IH and NT2 depending on sleep lab test outcomes. He said Alkermes expects significant overlap among NT1, NT2, and IH populations, and believes the orexin agonist efficacy signal can “power through” baseline heterogeneity because it targets core wakefulness circuitry.
Looking ahead to the SLEEP meeting, Pops said Alkermes plans to provide more insight into its NT2 data beyond headline average MWT deltas, which he said can appear unimpressive without context. He characterized the study as the only one conducted in a cohort of “pure NT2 patients” showing that kind of response across the observed variability.
Pricing framework and expansion beyond narcolepsy
Asked about pricing expectations—particularly given Takeda’s likely role in setting the initial benchmark—Pops said the U.S. market is now “post-IRA” and that, for “true orphan” disease-modifying drugs, average launch prices are between $300,000 and $400,000. He said an NT1-only orexin agonist that replaces a deficient neurotransmitter and shows unusually strong efficacy would be priced similarly to other disease-modifying orphan medicines, and he stated he would not use oxybates as the reference price.
Pops also cited “MFN” as a factor affecting global pricing strategy, warning that lower prices outside the U.S. could rapidly influence U.S. pricing. He said the industry is grappling with how to expand access internationally without creating pricing pressure in the U.S.
Beyond sleep disorders, Pops said Alkermes began planning for additional indications after presupposing narcolepsy would be successful, framing orexin agonists as tools to “safely interrogate” the brain’s wakefulness circuitry. He highlighted two near-term focus areas:
- ADHD: Pops cited animal model translatability and said Alkermes’ work suggests orexin agonist monotherapy “looks superior” to other approaches. Operationally, he said Alkermes plans to start a “big phase II study” in ADHD this year even before receiving phase 1b data, alongside a phase 1b translational study using biomarkers and electrophysiology to confirm circuit engagement.
- Fatigue (including MS and Parkinson’s): Pops said fatigue is a major unmet need, especially in multiple sclerosis, and that Alkermes has seen compelling fatigue-related data in narcolepsy patients. He described the regulatory pathway as less defined than ADHD because there are no clear precedents, though he noted validated endpoints exist and said the company has already discussed PROMIS-Fatigue and other scales with FDA in the context of narcolepsy.
The discussion also touched on LUMRYZ and idiopathic hypersomnia. Pops said Alkermes views IH as “very, very value-adding” for the product and placed a contingent value right (CVR) around the IH outcome because, while the clinical trial was ongoing, the design mirrors a prior oxybate approval in IH. He said there was “nothing a priori” suggesting the IH study should not work.
On longer-term market dynamics, Pops said conversations with patients and clinicians reinforced that oxybates represent a meaningful lifestyle burden and are primarily valued for consolidating nighttime sleep rather than delivering large daily wakefulness gains on MWT. He said once-nightly LUMRYZ could expand within the oxybate segment because many patients dislike waking for a second nightly dose, and he also argued that narcolepsy remains underdiagnosed—potentially expanding the overall treated population over time, which could also expand the number of patients for whom oxybates remain appropriate.
About Alkermes (NASDAQ:ALKS)
Alkermes plc is a biopharmaceutical company focused on developing innovative medicines to address unmet needs in the central nervous system (CNS). The company applies its proprietary drug delivery technologies and therapeutic expertise to advance treatments for addiction, schizophrenia, bipolar I disorder and depression. Alkermes’ portfolio includes both commercial products and a pipeline of investigational therapies designed to improve patient outcomes and support long-term disease management.
Alkermes’ commercial franchise features several approved products.
