Harmony Biosciences Receives FDA Approval for Expanded Use of WAKIX

Harmony Biosciences announced the U.S. Food and Drug Administration (FDA) has approved WAKIX® (pitolisant) for the treatment of cataplexy in adult patients with narcolepsy. WAKIX is the first and only treatment approved by the FDA for people with excessive daytime sleepiness or cataplexy associated with narcolepsy that is not scheduled as a controlled substance by the U.S. Drug Enforcement Administration. WAKIX received FDA approval for the treatment of excessive daytime sleepiness in adult patients with narcolepsy in August 2019.

"All people living with narcolepsy have excessive daytime sleepiness and up to two-thirds of them also experience cataplexy, which is one of the most debilitating symptoms of this chronic, rare neurological disorder," said Harmony's Chief Medical Officer, Jeffrey Dayno, M.D. "Today's FDA approval of the cataplexy indication for WAKIX, coupled with it being the first and only non-scheduled treatment option approved for adult patients with narcolepsy to treat both excessive daytime sleepiness or cataplexy, provides an opportunity for WAKIX to offer broad clinical utility to healthcare professionals managing adult patients living with narcolepsy."

"This approval underscores our ongoing commitment to support people who are living with narcolepsy," said John C. Jacobs, Harmony's President and Chief Executive Officer. "At Harmony, we always keep patients at the heart of all we do and with this approval, we are inspired to continue our mission to develop novel treatment options for those living with rare, neurological disorders who have unmet medical needs."

"From the very beginning, our passion at Bioprojet has been to bring WAKIX to people living with the daily challenges that are associated with impaired wakefulness and the risk of cataplexy attacks. This approval highlights the recognition by the FDA of a new therapeutic option in the treatment of the two major symptoms of narcolepsy by a drug with a novel mechanism of action," said Professor Jean-Charles Schwartz, PhD. Professor Schwartz is the discoverer of histaminergic neurotransmission in the brain and the histamine-3 receptor, which is the target receptor of WAKIX. He is also the co-founder, with Jeanne-Marie Lecomte, of Bioprojet.

WAKIX, a first-in-class medication, is a selective histamine 3 (H₃) receptor antagonist/inverse agonist that works through a novel mechanism of action to increase the synthesis and release of histamine, a wake-promoting neurotransmitter in the brain. WAKIX is administered orally, once daily in the morning upon wakening.

FDA approval of WAKIX for the treatment of cataplexy in adult patients with narcolepsy is based on the results from two randomized, controlled trials (HARMONY CTP and HARMONY 1) from the clinical development program for WAKIX. After a complete response letter (CRL) for the cataplexy indication was issued by the FDA in August 2019, Harmony met with the Agency in December 2019 to discuss the deficiencies cited in the CRL. After that meeting, the FDA agreed to review the reanalysis of the HARMONY 1 data that were submitted during the NDA review, after which the Agency acknowledged that those analyses confirmed that a statistically significant reduction in the rate of cataplexy for WAKIX compared to placebo was demonstrated, which supported the positive results from the HARMONY CTP trial. Subsequently, the FDA recommended that Harmony submit a resubmission to the CRL, which Harmony submitted in August 2020 and has led to today's FDA approval of the cataplexy indication for WAKIX.

Cataplexy is characterized by sudden, temporary loss of muscle tone and is often triggered by strong emotions, such as excitement or laughter. Cataplexy can be subtle, such as drooping of eyelids, or severe, such as knee buckling or total body collapse. Cataplexy may often go unrecognized because of the subtle nature of the symptoms in some patients, variability of how cataplexy is expressed, and/or lack of patient complaints or physician recognition of the symptoms as manifestations of cataplexy. Up to two-thirds of all patients with narcolepsy have cataplexy, which can have a significant impact on a person's daily functioning.

WAKIX, a first-in-class medication, was approved by the U.S. Food and Drug Administration in August 2019 for the treatment of excessive daytime sleepiness in adult patients with narcolepsy and has been commercially available in the U.S. since Q4 2019. It was granted orphan drug designation for the treatment of narcolepsy in 2010. 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.