Harmony Biosciences has announced plans to begin a Phase 3 study of Pitolisant for individuals with Prader-Willi syndrome ages 6 and up in the 4th quarter of 2023. This announcement is made following a positive end-of-phase 2 meeting with the FDA. Harmony's Phase 2 Pitolisant study with individuals with PWS showed overall improvement in daytime sleepiness on the ESS-CHAD Parent/Caregiver Version by 3.7 to 5.5 points.
"We are pleased with the outcome of our End-of-Phase 2 meeting with the FDA as we prepare to initiate our Phase 3 registrational study, which aims to further investigate the efficacy and safety of pitolisant as a potential treatment for excessive daytime sleepiness in individuals with Prader-Willi syndrome," said Kumar Budur, MD, Chief Medical Officer at Harmony Biosciences. "Building upon the encouraging data obtained from our Phase 2 signal detection study, we remain committed to advancing our development program for pitolisant in pursuit of a new indication in people with PWS, given the high unmet medical need in this population.”
Read Harmony Biosciences' full press release below.
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July 20, 2023
Harmony Biosciences Holdings, Inc. (“Harmony”) (Nasdaq: HRMY), a pharmaceutical company dedicated to developing and commercializing innovative therapies for patients with rare neurological diseases, has successfully completed an End-of-Phase 2 meeting with FDA regarding its clinical development plan evaluating pitolisant as a potential treatment for excessive daytime sleepiness (EDS) in patients ages six and older with Prader-Willi syndrome (PWS). Harmony plans to initiate a Phase 3 registrational study in the fourth quarter of 2023.
Based on a positive signal observed from the Phase 2 proof-of-concept study, Harmony aligned with the FDA on the proposed Phase 3 study design elements to support further investigation of pitolisant for children, adolescents and adults with PWS experiencing EDS. There is currently no FDA-approved treatment for EDS in this patient population.
"We are pleased with the outcome of our End-of-Phase 2 meeting with the FDA as we prepare to initiate our Phase 3 registrational study, which aims to further investigate the efficacy and safety of pitolisant as a potential treatment for excessive daytime sleepiness in individuals with Prader-Willi syndrome," said Kumar Budur, MD, Chief Medical Officer at Harmony Biosciences. "Building upon the encouraging data obtained from our Phase 2 signal detection study, we remain committed to advancing our development program for pitolisant in pursuit of a new indication in people with PWS, given the high unmet medical need in this population.”
There are currently 15,000 – 20,000 people in the US living with PWS, a genetic condition often diagnosed in childhood. More than half of patients experience EDS.
Pitolisant is marketed as WAKIX® in the U.S. and is FDA approved to treat EDS or cataplexy in adult patients with narcolepsy. Pitolisant is not approved for use in patients with PWS and is currently being evaluated as an investigational agent in this patient population.
About Prader-Willi Syndrome
PWS is an orphan/rare, genetic neurological disorder with many of the symptoms resulting from hypothalamic dysfunction. The hypothalamus is the part of the brain that controls both sleep-wake state stability and signals that mediate the balance between hunger and satiety, resulting in two of the main symptoms in patients with PWS, EDS and hyperphagia (an intense persistent sensation of hunger accompanied by food preoccupations, an extreme drive to consume food, food-related behavior problems, and a lack of normal satiety). Other features include low muscle tone, short stature, behavioral problems, and cognitive impairment. Approximately 15,000 to 20,000 people in the U.S. live with PWS, and over half of them experience EDS.
About WAKIX® (pitolisant) Tablets WAKIX, a first-in-class medication, is approved by the U.S. Food and Drug Administration for the treatment of excessive daytime sleepiness or cataplexy 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, 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 United States.
Indications and Usage WAKIX is indicated for the treatment of excessive daytime sleepiness or cataplexy in adult patients with narcolepsy.
Important Safety Information Contraindications 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 hepatic or renal impairment due to higher concentrations of pitolisant; monitor these patients for increased QTc. Dosage modification is recommended in patients with moderate hepatic impairment and moderate or severe renal impairment (see full prescribing information). WAKIX is not recommended in patients with end-stage renal disease (ESRD).
Adverse Reactions 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.
Drug Interactions 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 (see full prescribing information).
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. Therefore, reduced effectiveness of sensitive CYP3A4 substrates may occur when used concomitantly with WAKIX. The effectiveness of hormonal contraceptives may be reduced when used with WAKIX and effectiveness may be reduced for 21 days after discontinuation of therapy.
Use in Specific Populations WAKIX may reduce the effectiveness of 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 in patients less than 18 years of age.
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.
WAKIX is not recommended in patients with end-stage renal disease. Dosage adjustment of WAKIX is recommended in patients with moderate or severe renal impairment.
Dosage reduction is recommended in patients known to be poor CYP2D6 metabolizers; these patients have higher concentrations of WAKIX than normal CYP2D6 metabolizers.
Please see the Full Prescribing Information for WAKIX for more information.
To report suspected adverse reactions, contact Harmony Biosciences at 1-800-833-7460 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
About Harmony Biosciences
At Harmony Biosciences, we specialize in developing and delivering treatments for rare neurological diseases that others often overlook. We believe that where empathy and innovation meet, a better life can begin for people living with neurological diseases. Established by Paragon Biosciences, LLC, in 2017 and headquartered in Plymouth Meeting, PA, our team of experts from a wide variety of disciplines and experiences is driven by our shared conviction that innovative science translates into therapeutic possibilities for our patients, who are at the heart of everything we do. For more information, please visit www.harmonybiosciences.com.
