Harmony Biosciences Holdings announced a favorable settlement agreement with Lupin Limited that secures patent protection for its narcolepsy drug WAKIX through 2030, marking a significant victory in the company's efforts to defend its intellectual property portfolio against generic competition.
Settlement Terms Delay Generic Entry
Under the agreement announced June 5, 2025, Lupin will receive a license to launch its generic version of WAKIX (pitolisant hydrochloride) no earlier than January 2030, or July 2030 if pediatric exclusivity applies. The settlement dismisses litigation in the United States District Court for the District of Delaware that arose from Lupin's Abbreviated New Drug Application (ANDA) seeking approval for a generic version of the sleep disorder medication.
The settlement reinforces the validity and strength of Harmony's intellectual property portfolio covering WAKIX, which represents the first and only non-scheduled FDA-approved treatment for excessive daytime sleepiness or cataplexy in adults with narcolepsy, as well as for treating excessive daytime sleepiness in pediatric patients 6 years of age and older with narcolepsy.
Patent Portfolio Strength Validated
Harmony's patent position received additional validation when the U.S. Patent Office Patent Trial and Appeal Board declined for the second time on July 31, 2024, to institute an Ex Parte Reexamination of the company's exclusively licensed polymorph patent for pitolisant hydrochloride. The Board's decision affirms the validity and enforceability of Harmony's patent estate.
The company is currently advancing next-generation formulations of pitolisant with utility patents filed that carry potential exclusivity extending to 2044. These formulations are designed to address ongoing unmet medical needs in patients living with narcolepsy and other central disorders of hypersomnolence.
Ongoing Generic Defense Strategy
While celebrating the Lupin settlement, Harmony emphasized its commitment to vigorously defending its intellectual property rights. The company continues litigating its consolidated patent infringement case against several other companies that have filed ANDAs seeking approval for generic versions of WAKIX.
WAKIX Clinical Profile and Market Position
WAKIX, a first-in-class medication, functions as a selective histamine 3 (H₃) receptor antagonist/inverse agonist. The drug received orphan drug designation for narcolepsy treatment in 2010 and breakthrough therapy designation for cataplexy treatment in 2018. Its mechanism of action involves increasing the synthesis and release of histamine, a wake-promoting neurotransmitter, though the exact mechanism remains unclear.
In placebo-controlled clinical trials conducted in patients with narcolepsy, the most common adverse reactions for WAKIX occurring in ≥5% of patients and at least twice the rate of placebo were insomnia (6%), nausea (6%), and anxiety (5%). In pediatric patients 6 years and older, the most common adverse reactions were headache (19%) and insomnia (7%).
The drug carries important safety considerations, including QT interval prolongation warnings and contraindications for patients with severe hepatic impairment or known hypersensitivity to pitolisant. Dosage modifications are required for patients with hepatic or renal impairment and those taking certain concomitant medications.
WAKIX was originally designed and developed by Bioprojet in France, with Harmony holding an exclusive license to develop, manufacture and commercialize pitolisant in the United States. The company, established by Paragon Biosciences in 2017 and headquartered in Plymouth Meeting, Pennsylvania, focuses on developing innovative therapies for patients with rare neurological diseases.
