Harmony Biosciences Reports Phase 1 Data for Orexin-2 Agonist BP-205, Reinforcing Best-in-Class Potential
Key Insights
Harmony Biosciences reported Phase 1 SAD data for BP-205 (search) showing favorable PK with ~25h half-life and Tmax of 30–75 minutes, supporting once-daily dosing and rapid onset.
BP-205 (search) demonstrated a clean safety profile with no serious TEAEs; most common AEs were headache (~10%), fatigue (~4%), and diarrhea (~3%).
The company will initiate Phase 1b in sleep-deprived volunteers in Q3 2026 and Phase 2 trials across multiple CNS indications in mid-2027.
Harmony Biosciences has unveiled initial single ascending dose (SAD) data from its Phase 1 study of BP-205 (search), an orexin-2 receptor (search) (OX2R) agonist, demonstrating favorable pharmacokinetic (PK) and safety/tolerability profiles that the company says reinforce its potential as a best-in-class agent. The data were disclosed alongside record second-quarter 2026 financial results for WAKIX (pitolisant), which posted $261.3 million in net revenue.
The Phase 1 SAD topline data in healthy volunteers showed a short time to maximum plasma concentration (Tmax) ranging from 30 to 75 minutes, suggesting the potential for rapid onset of efficacy. The mean half-life (T1/2) of approximately 25 hours across dose groups supports once-a-day dosing and the possibility of durable efficacy throughout the day and into the early evening. Dose-proportional exposure was observed in both maximum observed plasma concentration (Cmax) and area under the curve (AUC), indicating predictable systemic exposure across the doses tested. No age or gender differences in PK parameters were noted, supporting the absence of dose adjustments for elderly or female patients.
BP-205 (search) was generally safe and well tolerated, with no serious or severe treatment-emergent adverse events (TEAEs) and no cardiovascular, hepatic, or visual abnormalities. The most common adverse events were headache, fatigue, and diarrhea, occurring in approximately 10%, 4%, and 3% of participants, respectively.
“The Phase 1 clinical PK and safety/tolerability data for BP-205 (search) that we shared today, together with pre-clinical data demonstrating the highest potency of any orexin-2 agonist currently in the clinic, reinforce our conviction that BP-205 has the potential to be the best-in-class orexin-2 agonist with broad clinical utility across multiple CNS indications,” said Jeffrey M. Dayno, MD, President and Chief Executive Officer of Harmony Biosciences.
Bruce C. Corser, MD, Medical Director of the Sleep Management Institute, added: “The Phase 1 single ascending dose pharmacokinetic and safety/tolerability data for BP-205 (search) are compelling. The potential for rapid onset of action and once-daily dosing, along with a favorable safety/tolerability profile, exceptional potency and high selectivity, suggests that BP-205 may have potential clinical utility in indications beyond orexin deficiency.”
Development Pathway for BP-205 (search)
BP-205 (search) (BP1.15205), discovered by Teijin Pharma (search) and developed in partnership with Bioprojet, is designed to deliver a differentiated profile through high potency, excellent selectivity, favorable safety/tolerability, and a predictable PK profile. Harmony describes it as the most potent OX2R agonist currently in clinical development.
The company outlined an aggressive development timeline: multiple ascending dose (MAD) data in healthy volunteers are expected in the fourth quarter of 2026. With the U.S. IND now open, Harmony will initiate a Phase 1b study in sleep-deprived healthy volunteers in the third quarter of 2026, with data expected in early 2027. Phase 2 studies evaluating multiple CNS indications are slated to begin in mid-2027.
WAKIX Commercial Performance
WAKIX net product revenue for the second quarter of 2026 reached $261.3 million, representing 30% year-over-year growth compared to $200.5 million in the same period of 2025. The estimated average number of patients grew by 450 to approximately 8,950, marking the second-highest average patient growth on record. Harmony reiterated its full-year 2026 WAKIX net revenue guidance of $1.0 billion to $1.04 billion.
Net income for the quarter was $75.4 million, or $1.28 per diluted share, compared to $39.8 million, or $0.68 per diluted share, in the prior-year period. Research and development expenses were $46.6 million, down 7% from $50.2 million in the second quarter of 2025. As of June 30, 2026, Harmony held cash, cash equivalents, and investments of $962.5 million.
Pipeline Expansion Beyond BP-205 (search)
Harmony is advancing multiple programs across its pitolisant franchise. A New Drug Application for pitolisant GR (gastro-resistant) tablets was accepted by the FDA in July, with a target PDUFA date of April 1, 2027. The formulation features an enteric coating designed to reduce gastrointestinal side effects and enables patients to initiate treatment at a therapeutic dose without titration.
Pitolisant HD (high dose) is being evaluated in two Phase 3 registrational trials: ONSTRIDE 1 in narcolepsy (search) and ONSTRIDE 2 in idiopathic hypersomnia (search) (IH), with topline data expected in 2027 and an anticipated PDUFA date in 2028. The enhanced formulation aims to drive greater efficacy through an optimized PK profile, enteric coating, and higher dose, with differentiated labeling targeting fatigue in narcolepsy and sleep inertia in IH.
Additionally, the Phase 3 TEMPO study of WAKIX in Prader-Willi syndrome (search) (PWS) is ongoing, with topline data expected in mid-2027 and an anticipated PDUFA date in 2028. Completion of the TEMPO study fulfills the second and final requirement agreed with the FDA for WAKIX pediatric exclusivity, which would provide an additional six months of regulatory exclusivity.
EPX-100 (clemizole hydrochloride) is actively enrolling in two global Phase 3 registrational trials in rare epilepsies: the LIGHTHOUSE Study in Lennox-Gastaut syndrome (search) and the ARGUS Study in Dravet syndrome (search), with topline data expected in the first half of 2027.