Ep200: Richard Pops on Orexin Drugs For Sleep Disorders & More

What It Covers

Richard Pops, 35-year CEO of Alkermes, discusses the company's late-stage development of elixirexant, an orexin-2 receptor agonist targeting narcolepsy type 1, with potential expansion into ADHD, MS fatigue, and Parkinson's. He also addresses mid-sized biopharma policy threats, including IRA pricing reforms, most-favored-nation pricing, and the rising competitive pressure from China.

Key Questions Answered

• •Orexin-2 agonist efficacy benchmark: In phase 2 NT1 trials, elixirexant raised maintenance of wakefulness test scores from a baseline of 3–5 minutes to above 20 minutes — surpassing all existing narcolepsy treatments. Patients simultaneously reported normalized scores on the British Columbia Cognitive Complaints Index and the PROMIS Fatigue Scale, suggesting the drug addresses brain fog and fatigue alongside sleepiness, not just eye-open wakefulness duration.
• •Pipeline expansion strategy: Alkermes has placed two additional orexin agonist compounds into phase 1 healthy volunteer studies, with one targeting ADHD and one targeting neurodegeneration-related fatigue in MS and Parkinson's patients. Both programs are expected to enter patient trials within the current year, following the GLP-1 model of starting in a severe disease population and expanding to broader indications as the safety database grows.
• •Cardiovascular and hepatic safety differentiation: Early orexin agonist candidates from Japanese developers showed unacceptable blood pressure and heart rate signals due to insufficient orexin-2 selectivity. Takeda's lead compound demonstrated liver toxicity traced to a specific metabolite, not an on-target effect. Alkermes addressed both risks by engineering higher potency and selectivity, reporting no clinically appreciable cardiovascular or hepatotoxic findings across their expanded phase 2 dataset.
• •Mid-sized biopharma policy vulnerability: Companies with $2B–$10B market caps — roughly 72 exist currently — face disproportionate harm from Part D redesign and MFN pricing. Alkermes pays over 50% gross-to-net deductions on Aristada to access Medicaid formularies. A proposed 20% manufacturer contribution on Part D revenues would have pushed Alkermes from profitable to unprofitable, a concrete outcome the Midsize Biotech Alliance of America (MBAA) used to successfully negotiate a phase-in exemption for smaller companies.
• •European pricing equilibrium shift: Under emerging MFN pricing pressure, companies should model ex-US revenue assuming European reimbursement prices will not rise to match US levels in the near term. European payers routinely decline reimbursement at US price points, effectively excluding patients in Germany, France, and Italy from novel therapies. Mid-sized companies with one or two products cannot absorb this revenue truncation the way large multinationals with diversified portfolios can.
• •PDUFA VII back-to-basics approach: The current PDUFA renegotiation cycle, effective 2027, prioritizes restoring FDA's core review sequence — IND through approval — rather than adding pilot programs or new statistical mandates. Industry user fees fund over 70% of new drug review budgets. The strategic goal is ensuring FDA has sufficient headcount and process transparency to reduce complete response letters and eliminate late-stage surprises that disproportionately damage smaller companies with concentrated pipelines.