Takeda Pharmaceutical Company (4502) Study Update summary

Study design and objectives

• Two global, randomized, double-blind, placebo-controlled phase III trials evaluated Oveporexton in narcolepsy type 1 (NT1), enrolling 273 adults with severe symptoms across multiple continents for 12 weeks of treatment.

• Trials assessed 14 primary and secondary endpoints, including excessive daytime sleepiness, cataplexy, cognition, nighttime symptoms, and quality of life, with dosing at 1 mg or 2 mg BID to mimic natural orexin tone.

• Over 95% of participants entered long-term extension studies, with some treated for over two years.

• Regulatory filings are planned for fiscal year 2025, with global commercial potential estimated at $2–3+ billion.

• Oveporexton is an oral orexin receptor 2 agonist developed to address the root cause of NT1 by restoring orexin signaling.

Key efficacy results

• Statistically significant and clinically meaningful improvements were observed on all endpoints, including MWT, ESS, and cataplexy frequency, at both 1 mg and 2 mg BID doses.

• Majority of patients achieved normalization in excessive daytime sleepiness, with 85% reaching normal ESS scores at 2 mg and most reaching normative wakefulness and sleepiness levels at 12 weeks.

• Cataplexy rates reduced by 80–90%, with most patients experiencing cataplexy-free days and sustained benefit over 12 months.

• Disease severity, as measured by NSS-CT, was significantly reduced, with over 70% reporting only mild symptoms after 12 weeks.

• Patient-reported outcomes indicated 69–79% had no or mild symptom severity, and 74–97% reported much or very much improved symptoms.

Quality of life and functioning

• Oveporexton led to significant improvements in both mental and physical components of the SF-36, exceeding clinically meaningful thresholds and bringing most patients to normative ranges.

• EQ-5D-5L index and VAS scores improved to normative values, with marked gains in usual activities, mobility, and reduced pain/discomfort and anxiety/depression.

• Improvements were observed across all domains of the Functional Impacts of Narcolepsy Instrument (FINI).

• Oveporexton demonstrated transformative improvements in functioning, quality of life, and patient-reported outcomes.