FDA Extends Harmony’s Wakix Approval to Pediatric Patients with Narcolepsy

Rare Daily Staff

The U.S. Food and Drug Administration has approved Harmony Biosciences’ supplemental New Drug Application for Wakix tablets for the treatment of excessive daytime sleepiness in pediatric patients 6 years of age and older with narcolepsy.

The FDA separated the submission into two sNDAs for administrative purposes to issue an approval for the treatment of excessive daytime sleepiness (EDS) and a complete response for the treatment of cataplexy in pediatric patients (6 to less than18 years of age) with narcolepsy.

The FDA granted priority review of the sNDA based on a phase 3 study conducted by Bioprojet, which evaluated the safety and efficacy of Wakix (pitolisant) in patients ages 6 to under 18 years with narcolepsy, with or without cataplexy. Based on the results of this study, Bioprojet received approval from the European Medicines Agency last year extending the indication for Wakix to include the treatment of narcolepsy in children ages 6 years of age and older, with or without cataplexy.

“EDS is the primary symptom experienced by all patients with narcolepsy and this approval for Wakix, as the first-and-only FDA-approved non-scheduled treatment option for narcolepsy, makes this important treatment option available to pediatric patients 6 years and older living with narcolepsy,” said Jeffrey Dayno, president and CEO of Harmony Biosciences.

Narcolepsy is a rare, chronic, debilitating neurological disease of sleep-wake state instability and is primarily characterized by its cardinal symptom excessive daytime sleepiness (EDS), with or without cataplexy – along with other manifestations of REM sleep dysregulation (hallucinations and sleep paralysis), which intrude into wakefulness. EDS is the inability to stay awake and alert during the day and is the symptom that is present in all people living with narcolepsy. In most patients, narcolepsy is caused by the loss of hypocretin/orexin, a neuropeptide in the brain that supports sleep-wake state stability. This disease affects men and women equally, with typical symptom onset in adolescence or young adulthood; however, it can take up to a decade to be properly diagnosed.

Wakix was first approved by the FDA in August 2019 for the treatment of EDS in adult patients with narcolepsy, followed by FDA approval for the treatment of cataplexy in adult patients with narcolepsy in October 2020. A first-in-class treatment with a novel mechanism of action, Wakix functions as a selective histamine 3 (H₃) receptor antagonist/inverse agonist that is believed to target the histamine system to promote wakefulness.

Wakix was granted orphan drug designation for the treatment of narcolepsy in 2010, and breakthrough therapy designation for the treatment of cataplexy in 2018. Wakix is a selective histamine 3 (H₃) receptor antagonist/inverse agonist. The mechanism of action of Wakix is unclear; however, its efficacy could be mediated through its activity at H₃ receptors, thereby increasing the synthesis and release of histamine, a wake promoting neurotransmitter. Wakix was designed and developed by Bioprojet. Harmony has an exclusive license from Bioprojet to develop, manufacture and commercialize pitolisant in the United States.

“The unique mechanism of action of Wakix and its non-scheduled status are especially important for a pediatric population that has had limited treatment options, all of which are controlled substances,” said Dayno. “We are currently working on the next-generation formulations that could potentially offer additional benefits to patients, such as greater efficacy and new indications, extend the Wakix franchise, and strengthen our leadership position in the treatment of rare sleep disorders.”

Harmony plans to discuss with the agency a path forward for a cataplexy indication in pediatric narcolepsy patients based on the strength of the existing data from Bioprojet’s phase 3 trial.

Photo: Jeffrey Dayno, president and CEO of Harmony Biosciences.