FDA Approves Lupin's Generic Pitolisant and Harmony's WAKIX for Pediatric Narcolepsy

The U.S. Food and Drug Administration (FDA) has granted final approval to Lupin Limited for its generic Pitolisant Tablets in 4.45 mg and 17.8 mg strengths, and separately approved Harmony Biosciences' supplemental new drug application (sNDA) for WAKIX (pitolisant) tablets for the treatment of cataplexy in pediatric narcolepsy. Lupin's tablets were approved as bioequivalent to WAKIX for the indications in the approved labelling.

The approved generic drug is bioequivalent to Harmony Biosciences' WAKIX (pitolisant), which is indicated for the treatment of excessive daytime sleepiness (EDS) or cataplexy in patients with narcolepsy. The once-daily therapy is designed to block histamine H3 receptors in the brain, to regulate the release of histamine and other wake-promoting chemicals to promote alertness and reduce excessive daytime sleepiness. Lupin did not disclose the drug's expected market potential and launch timeline.

WAKIX, a first-in-class medication, is now the first-and-only FDA-approved treatment option for both pediatric and adult narcolepsy patients with or without cataplexy that is not scheduled as a controlled substance. WAKIX is indicated for the treatment of excessive daytime sleepiness (EDS) or cataplexy in patients 6 years of age and older with narcolepsy.

WAKIX is contraindicated in patients with known hypersensitivity to pitolisant or any component of the formulation, and in patients with severe hepatic impairment. WAKIX prolongs the QT interval; avoid use in patients with known QT prolongation or in combination with other drugs known to prolong the QT interval. In placebo-controlled clinical trials in patients with narcolepsy with or without cataplexy, the most common adverse reactions (≥5% and at least twice placebo) for WAKIX were insomnia (6%), nausea (6%), and anxiety (5%). In the pediatric clinical trial, the most common adverse reactions (≥5% and greater than placebo) were headache (19%) and insomnia (7%).

Concomitant administration of WAKIX with strong CYP2D6 inhibitors increases pitolisant exposure by 2.2-fold, requiring a dose reduction by half. Concomitant use with strong CYP3A4 inducers decreases exposure by 50%, and dosage adjustments may be required. WAKIX is a borderline/weak inducer of CYP3A4 and may reduce the effectiveness of sensitive CYP3A4 substrates, including hormonal contraceptives; patients using hormonal contraception should use an alternative non-hormonal method during treatment and for at least 21 days after discontinuing treatment.

Lupin is a Mumbai-based global pharmaceutical company that distributes products in over 100 markets. The company specialises in branded and generic formulations, complex generics, biotechnology products, and active pharmaceutical ingredients. It operates 15 manufacturing sites and six research centres globally, employing over 26,000 professionals.