Harmony Biosciences, announced that the US Food and Drug Administration (FDA) has approved its supplemental new drug application (sNDA) for Wakix (pitolisant) tablets for the treatment of cataplexy in paediatric patients 6 years of age and older with narcolepsy. Wakix is now the first-and-only US FDA-approved non-scheduled treatment for paediatric and adult narcolepsy patients with or without cataplexy.
“We are excited to achieve this important milestone for paediatric narcolepsy patients who experience cataplexy,” said Kumar Budur, chief medical and scientific officer of Harmony Biosciences. “With this approval, clinicians now have the option to prescribe Wakix to treat excessive daytime sleepiness, cataplexy, or both, in patients 6 years and older with narcolepsy.”
Wakix was approved by the US FDA in August 2019 for the treatment of excessive daytime sleepiness (EDS) in adult patients with narcolepsy, with approval expanded to include cataplexy in adult patients in October 2020. The FDA approved Wakix for the treatment of EDS in paediatric patients 6 years of age and older with narcolepsy in June 2024.
“Wakix is now the first-and-only FDA-approved treatment option for both paediatric and adult narcolepsy patients with or without cataplexy that is not scheduled as a controlled substance, an important distinction that supports its clinical utility,” said Jeffrey M. Dayno, president and chief executive officer of Harmony Biosciences. “We continue to advance our efforts toward obtaining paediatric exclusivity for Wakix, which, if granted, would add an additional six months of regulatory exclusivity for this growing franchise. Our sights are now set on further growing, extending and expanding the value of pitolisant through additional indications with our next-generation formulations, which have utility patents filed out to 2044.”
Wakix, a first-in-class medication, is approved by the US FDA for the treatment of excessive daytime sleepiness (EDS) or cataplexy in patients 6 years of age and older with narcolepsy. It 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 (France). Harmony has an exclusive license from Bioprojet to develop, manufacture and commercialize pitolisant in the US.
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. Anaphylaxis has been reported. Wakix is also contraindicated in patients with severe hepatic impairment.
Warnings and precautions:
Wakix prolongs the QT interval; avoid use of Wakix in patients with known QT prolongation or in combination with other drugs known to prolong the QT interval. Avoid use in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and the presence of congenital prolongation of the QT interval.
The risk of QT prolongation may be greater in patients with higher concentrations of pitolisant (e.g., patients with hepatic or renal impairment). Monitor patients with hepatic or renal impairment for increased QTc. Dosage modification is recommended in patients with moderate hepatic impairment and moderate or severe renal impairment. Wakix is contraindicated in patients with severe hepatic impairment and not recommended in patients with end-stage renal disease (ESRD).
In the placebo-controlled clinical trials conducted 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%). Other adverse reactions that occurred at =2% and more frequently than in patients treated with placebo included headache, upper respiratory tract infection, musculoskeletal pain, heart rate increased, hallucinations, irritability, abdominal pain, sleep disturbance, decreased appetite, cataplexy, dry mouth, and rash. In the placebo-controlled phase of the clinical trial conducted in paediatric patients 6 years and older with narcolepsy with or without cataplexy, the most common adverse reactions (=5% and greater than placebo) for Wakix were headache (19%) and insomnia (7%). The overall adverse reaction profile of Wakix in the paediatric clinical trial was similar to that seen in the adult clinical trial programme.
Concomitant administration of Wakix with strong CYP2D6 inhibitors increases pitolisant exposure by 2.2-fold. Reduce the dose of Wakix by half.
Concomitant use of Wakix with strong CYP3A4 inducers decreases exposure of pitolisant by 50%. Dosage adjustments may be required.
H1 receptor antagonists that cross the blood-brain barrier may reduce the effectiveness of Wakix. Patients should avoid centrally acting H1 receptor antagonists.
Wakix is a borderline/weak inducer of CYP3A4. Wakix may reduce the effectiveness of sensitive CYP3A4 substrates, including hormonal contraceptives. Patients using hormonal contraception should be advised to use an alternative non-hormonal contraceptive method during treatment with Wakix and for at least 21 days after discontinuing treatment.
There is a pregnancy exposure registry that monitors pregnancy outcomes in women who are exposed to Wakix during pregnancy. Patients should be encouraged to enroll in the Wakix pregnancy registry if they become pregnant. To enroll or obtain information from the registry, patients can call 1-800-833-7460.
The safety and effectiveness of WAKIX have not been established for the treatment of excessive daytime sleepiness or cataplexy in pediatric patients less than 6 years of age with narcolepsy.
WAKIX is extensively metabolized by the liver. WAKIX is contraindicated in patients with severe hepatic impairment. Dosage adjustment is required in patients with moderate hepatic impairment.
The maximum recommended dosage is lower in patients who are CYP2D6 poor metabolizers because these patients have higher pitolisant concentrations than CYP2D6 normal metabolizers and may have increased risk of adverse events.