Harmony Biosciences Provides Update on the Status of the Supplemental New Drug Application for Pitolisant in Idiopathic Hypersomnia
Harmony Biosciences (NASDAQ: HRMY) received a Refusal to File (RTF) letter from the FDA for pitolisant in treating excessive daytime sleepiness in adult patients with idiopathic hypersomnia (IH). Despite this setback, the company maintains its 2025 net revenue guidance of $820-$860 million.
The company's long-term strategy focuses on Pitolisant HD, an enhanced higher-dose formulation with patent protection until 2044. Harmony plans to initiate a Phase 3 registrational trial of Pitolisant HD in IH in Q4 2025, targeting a PDUFA date in 2028.
While the Phase 3 INTUNE Study's primary outcome didn't reach statistical significance, open-label phase data showed patient improvements five times greater than clinically meaningful levels on the Epworth Sleepiness Scale. The majority of patients maintained normal wakefulness levels beyond one year in the long-term extension study.
Harmony Biosciences (NASDAQ: HRMY) ha ricevuto una lettera di Rifiuto alla Presentazione (RTF) dalla FDA per il pitolisant nel trattamento della sonnolenza diurna eccessiva in pazienti adulti con ipersomnia idiopatica (IH). Nonostante questo contrattempo, l'azienda mantiene le sue previsioni di fatturato netto per il 2025 di 820-860 milioni di dollari.
La strategia a lungo termine dell'azienda si concentra su Pitolisant HD, una formulazione potenziata a dose più alta con protezione brevettuale fino al 2044. Harmony prevede di avviare un trial registrativo di Fase 3 di Pitolisant HD in IH nel quarto trimestre del 2025, puntando a una data PDUFA nel 2028.
Sebbene l'esito primario dello Studio INTUNE di Fase 3 non abbia raggiunto la significatività statistica, i dati della fase open-label hanno mostrato miglioramenti nei pazienti cinque volte superiori ai livelli clinicamente significativi sulla Scala di Sonno di Epworth. La maggior parte dei pazienti ha mantenuto livelli normali di vigilanza oltre un anno nello studio di estensione a lungo termine.
Harmony Biosciences (NASDAQ: HRMY) recibió una carta de Rechazo a la Presentación (RTF) de la FDA para el pitolisant en el tratamiento de la somnolencia diurna excesiva en pacientes adultos con hipersomnia idiopática (IH). A pesar de este contratiempo, la compañía mantiene su guía de ingresos netos para 2025 de 820-860 millones de dólares.
La estrategia a largo plazo de la compañía se centra en Pitolisant HD, una formulación mejorada de dosis más alta con protección de patente hasta 2044. Harmony planea iniciar un ensayo registrativo de Fase 3 de Pitolisant HD en IH en el cuarto trimestre de 2025, con una fecha PDUFA prevista para 2028.
Aunque el resultado primario del Estudio INTUNE de Fase 3 no alcanzó significación estadística, los datos de la fase abierta mostraron mejoras en los pacientes cinco veces mayores que los niveles clínicamente significativos en la Escala de Somnolencia de Epworth. La mayoría de los pacientes mantuvieron niveles normales de vigilia más allá de un año en el estudio de extensión a largo plazo.
하모니 바이오사이언스 (NASDAQ: HRMY)는 특발성 과다 수면증 (IH) 성인 환자의 주간 과다 졸림 치료를 위한 피톨리산에 대해 FDA로부터 제출 거부(RTF) 통지를 받았습니다. 이러한 차질에도 불구하고 회사는 2025년 순수익 가이던스를 8억 2천만 - 8억 6천만 달러로 유지하고 있습니다.
회사의 장기 전략은 2044년까지 특허 보호를 받는 향상된 고용량 제형인 피톨리산 HD에 중점을 두고 있습니다. 하모니는 2025년 4분기에 IH에 대한 피톨리산 HD의 3상 등록 시험을 시작할 계획이며, 2028년 PDUFA 날짜를 목표로 하고 있습니다.
3상 INTUNE 연구의 주요 결과는 통계적 유의성을 달성하지 못했지만, 공개 라벨 단계 데이터는 환자 개선이 에포스 수면 척도에서 임상적으로 의미 있는 수준보다 5배 더 높음을 보여주었습니다. 대부분의 환자는 장기 연장 연구에서 1년 이상 정상적인 각성 수준을 유지했습니다.
Harmony Biosciences (NASDAQ: HRMY) a reçu une lettre de Refus de Dépôt (RTF) de la FDA concernant le pitolisant pour le traitement de la somnolence diurne excessive chez les patients adultes atteints d'hypersomnie idiopathique (IH). Malgré ce revers, l'entreprise maintient ses prévisions de revenus nets pour 2025 entre 820 et 860 millions de dollars.
La stratégie à long terme de l'entreprise se concentre sur Pitolisant HD, une formulation améliorée à dose plus élevée bénéficiant d'une protection par brevet jusqu'en 2044. Harmony prévoit de lancer un essai d'enregistrement de Phase 3 de Pitolisant HD en IH au quatrième trimestre 2025, visant une date PDUFA en 2028.
Bien que le résultat principal de l'Étude INTUNE de Phase 3 n'ait pas atteint de signification statistique, les données de phase ouverte ont montré des améliorations chez les patients cinq fois supérieures aux niveaux cliniquement significatifs sur l'Échelle de Somnolence d'Epworth. La majorité des patients ont maintenu des niveaux de vigilance normaux au-delà d'un an dans l'étude d'extension à long terme.
Harmony Biosciences (NASDAQ: HRMY) hat einen Ablehnungsbescheid (RTF) von der FDA für Pitolisant zur Behandlung von übermäßiger Tagesmüdigkeit bei erwachsenen Patienten mit idiopathischer Hypersomnie (IH) erhalten. Trotz dieses Rückschlags bleibt das Unternehmen bei seiner Prognose für den Nettoumsatz im Jahr 2025 von 820-860 Millionen US-Dollar.
Die langfristige Strategie des Unternehmens konzentriert sich auf Pitolisant HD, eine verbesserte Hochdosisformulierung mit Patentschutz bis 2044. Harmony plant, im 4. Quartal 2025 eine registrierte Phase-3-Studie von Pitolisant HD bei IH zu starten, mit dem Ziel eines PDUFA-Datums im Jahr 2028.
Obwohl das primäre Ergebnis der Phase-3-Studie INTUNE keine statistische Signifikanz erreichte, zeigten Daten aus der offenen Phase, dass die Verbesserungen der Patienten fünfmal größer waren als klinisch signifikante Werte auf der Epworth-Schläfrigkeitsskala. Die Mehrheit der Patienten hielt die normalen Wachheitsniveaus über ein Jahr im Langzeitverlängerungsstudie aufrecht.
- 2025 revenue guidance of $820-$860 million remains unchanged
- Pitolisant HD patent protection extends to 2044
- Strong open-label phase results showing 5x improvement over clinical significance threshold
- FDA Refusal to File letter for pitolisant in IH treatment
- Phase 3 INTUNE Study failed to reach statistical significance in primary outcome
- Delayed market entry with new PDUFA target in 2028
Insights
The FDA's Refusal to File (RTF) for Harmony's pitolisant sNDA reveals important strategic dynamics at play. While representing a near-term setback, the maintenance of
The strategic pivot to Pitolisant HD emerges as a calculated long-term play. The enhanced formulation, protected by patents through 2044, offers several advantages over the current submission:
- Optimized dosing profile potentially leading to better efficacy
- Extended market exclusivity providing significant commercial runway
- Opportunity to address FDA concerns comprehensively in the new Phase 3 program
The INTUNE Study results, while mixed, demonstrate clinical potential - patients showed improvements five times greater than the clinically meaningful threshold on the Epworth Sleepiness Scale during the open-label phase. This suggests strong efficacy signals that could be better captured in the upcoming Pitolisant HD trials.
The company's strategic decision to proceed with the original sNDA, despite challenges, indicates aggressive pursuit of market opportunities while maintaining a parallel, more robust development path. The planned Phase 3 trial initiation in Q4 2025 with a 2028 PDUFA target represents a methodical approach to market entry, albeit delayed. This dual-track strategy - attempting an earlier entry while developing an enhanced formulation - demonstrates sophisticated portfolio management, even though the near-term pathway proved unsuccessful.
“We are disappointed with this short-term setback, but our long-term strategy for pitolisant in IH remains firmly on track with our focus on Pitolisant HD,” said Jeffrey M. Dayno, M.D.,
“Our planned Phase 3 registrational trial, a double-blind, randomized, parallel-group study in patients with IH, is based on input from the FDA,” said Kumar Budur, M.D., M.S., Chief Medical and Scientific Officer at Harmony Biosciences. “We believe this study design will effectively demonstrate the benefit of pitolisant in patients with IH based on the robust clinical response that was observed in the Phase 3 INTUNE Study. We are grateful to the patients and clinicians who participated in the INTUNE Study, and our commitment to these patients remains steadfast. With the initiation of this pivotal Phase 3 trial in Q4 2025, we will continue to advance pitolisant-based treatments to address their unmet needs.”
Although the primary outcome for EDS between pitolisant and placebo did not reach statistical significance in the randomized withdrawal phase of the Phase 3 INTUNE Study, the data from the open-label phase showed that patients experienced improvements on the Epworth Sleepiness Scale that were five times greater than what is recognized as clinically meaningful. Furthermore, the majority of patients in the long-term extension study achieved normal levels of wakefulness and sustained this response beyond one year.
Harmony’s diversified pipeline and commitment to advancing science in sleep/wake and rare neurological disorders remain key drivers of its long-term vision. The company continues to execute on its strategic priorities and is confident in its ability to deliver sustained growth.
Pitolisant is marketed as WAKIX® in the
About WAKIX® (pitolisant) Tablets
WAKIX, a first-in-class medication, is approved by the
Indications and Usage
WAKIX is indicated for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adult patients with narcolepsy and for the treatment of excessive daytime sleepiness (EDS) in pediatric patients 6 years of age and older 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. WAKIX is contraindicated in patients with severe hepatic impairment and 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 (≥
In the placebo-controlled phase of the clinical trial conducted in pediatric patients 6 years and older with narcolepsy with or without cataplexy, the most common adverse reactions (≥
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
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.
Use in Specific Populations
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 treatment of excessive daytime sleepiness in pediatric patients less than 6 years of age with narcolepsy.
The safety and effectiveness of WAKIX have not been established for treatment of cataplexy in pediatric patients 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.
WAKIX is not recommended in patients with end-stage renal disease. Dosage adjustment of WAKIX is recommended in patients with eGFR <60 mL/minute/1.73 m2.
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 Idiopathic Hypersomnia
Idiopathic Hypersomnia (IH) is a rare and chronic neurological disease that is characterized by excessive daytime sleepiness (EDS) despite sufficient or even long sleep time. EDS in IH cannot be alleviated by naps, longer sleep or more efficient sleep. People living with IH experience significant EDS along with the symptoms of sleep inertia (prolonged difficulty waking up from sleep) and 'brain fog' (impaired cognition, attention, and alertness). The cause of IH is unknown, but it is likely due to alterations in areas of the brain that stabilize states of sleep and wakefulness. IH is one of the central disorders of hypersomnolence and, like narcolepsy, is a debilitating sleep disorder that can result in significant disruption in daily functioning.
About Harmony Biosciences
Harmony Biosciences is a pharmaceutical company dedicated to developing and commercializing innovative therapies for patients with rare neurological diseases who have unmet medical needs. Driven by novel science, visionary thinking, and a commitment to those who feel overlooked, Harmony Biosciences is nurturing a future full of therapeutic possibilities that may enable patients with rare neurological diseases to truly thrive. Established by Paragon Biosciences, LLC, in 2017 and headquartered in
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including statements regarding our full year 2024 net product revenue, expectations for the growth and value of WAKIX, plans to submit an sNDA for pitolisant in idiopathic hypersomnia; our future results of operations and financial position, business strategy, products, prospective products, product approvals, the plans and objectives of management for future operations and future results of anticipated products. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our commercialization efforts and strategy for WAKIX; the rate and degree of market acceptance and clinical utility of pitolisant in additional indications, if approved, and any other product candidates we may develop or acquire, if approved; our research and development plans, including our plans to explore the therapeutic potential of pitolisant in additional indications; our ongoing and planned clinical trials; our ability to expand the scope of our license agreements with Bioprojet Société Civile de Recherche (“Bioprojet”); the availability of favorable insurance coverage and reimbursement for WAKIX; the timing of, and our ability to obtain, regulatory approvals for pitolisant for other indications as well as any other product candidates; our estimates regarding expenses, future revenue, capital requirements and additional financing needs; our ability to identify, acquire and integrate additional products or product candidates with significant commercial potential that are consistent with our commercial objectives; our commercialization, marketing and manufacturing capabilities and strategy; significant competition in our industry; our intellectual property position; loss or retirement of key members of management; failure to successfully execute our growth strategy, including any delays in our planned future growth; our failure to maintain effective internal controls; the impact of government laws and regulations; volatility and fluctuations in the price of our common stock; the significant costs and required management time as a result of operating as a public company; the fact that the price of Harmony's common stock may be volatile and fluctuate substantially; statements related to our intended share repurchases and repurchase timeframe and the significant costs and required management time as a result of operating as a public company. These and other important factors discussed under the caption "Risk Factors" in our Annual Report on Form 10-K filed with the Securities and Exchange Commission (the "SEC") on February 22, 2024, and our other filings with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.
View source version on businesswire.com: https://www.businesswire.com/news/home/20250219512387/en/
Harmony Biosciences Investor Contact:
Brennan Doyle
484-539-9700
bdoyle@harmonybiosciences.com
Harmony Biosciences Media Contact:
Cate McCanless
202-641-6086
cmccanless@harmonybiosciences.com
Source: Harmony Biosciences Holdings, Inc.
FAQ
What impact does the FDA's Refusal to File have on HRMY's 2025 revenue guidance?
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