PLYMOUTH MEETING, Pa., Oct. 13, 2023 /PRNewswire/ -- Harmony Biosciences Holdings, Inc. ('Harmony' or the 'Company') (Nasdaq: HRMY), a pharmaceutical company dedicated to developing and commercializing innovative therapies for patients with rare neurological diseases, today announced topline results from the INTUNE study in patients with idiopathic hypersomnia (IH)..

宾夕法尼亚州普利茅斯会议，2023年10月13日/PRNewswire/-Harmony Biosciences Holdings，Inc。（'Harmony'或'公司'）（纳斯达克股票代码：HRMY），一家致力于开发和商业化创新疗法的制药公司对于罕见的神经系统疾病患者，今天宣布INTUNE研究在特发性嗜睡（IH）患者中的顶级结果。。

Kumar Budur, M.D., Chief Medical Officer at Harmony Biosciences said, 'We are very encouraged by the magnitude of the response seen in the initial open-label treatment period, where 83% of patients completing this phase responded with an average 9.4 point improvement in the Epworth Sleepiness Scale (ESS).

Harmony Biosciences的首席医疗官Kumar Budur博士说：“我们对初始开放标签治疗期间的反应程度非常鼓舞，完成这一阶段的83%的患者反应平均提高了9.4分。Epworth嗜睡量表（ESS）。

Equally encouraging is the number of patients, almost 90%, electing to continue into the long-term extension study, allowing us to generate additional safety and efficacy data in this patient population. Positive trends in other important outcomes like sleep inertia add to the totality of evidence that pitolisant has a clinical benefit for patients with IH.'.

同样令人鼓舞的是，选择继续进行长期延长研究的患者人数接近90%，使我们能够在该患者群体中产生额外的安全性和有效性数据。睡眠惯性等其他重要结果的积极趋势增加了pitolisant对IH患者具有临床益处的全部证据。

The INTUNE study was a Phase 3 placebo-controlled, double-blind, randomized withdrawal study. Approximately 83% of patients who completed the 8-week open-label treatment period with pitolisant were responders (as defined by a decrease on the ESS of ≥3 points) and experienced a robust clinical response, with an average ESS change from baseline of – 9.4 points.

INTUNE研究是一项3期安慰剂对照，双盲，随机戒断研究。大约83%的患者完成了8周的开放标签治疗期与pitolisant是有效的（定义为ESS下降≥3分），并经历了一个强大的临床反应，平均ESS变化从基线-9.4分。

A positive trend favoring pitolisant was observed during the 4-week double-blind randomized withdrawal period, however no statistically significant difference was observed between pitolisant and placebo groups on ESS, the primary endpoint. Positive trends favoring pitolisant were also observed across additional prespecified endpoints including the IHSS, which approached statistical significance, as well as on the SlQ.

在4周双盲随机停药期间观察到有利于pitolisant的积极趋势，但在主要终点ESS上，pitolisant组和安慰剂组之间没有观察到统计学上的显着差异。在其他预先设定的终点（包括接近统计学显着性的IHSS）以及SlQ上也观察到有利于pitolisant的积极趋势。

Further data analyses are being conducted. Approximately 88% of patients in the study continued into a 12-month long-term extension study, which is ongoing. The safety and tolerability profile of pitolisant in adult patients with idiopathic hypersomnia was consistent with the established safety profile and no new safety signals were observed..

正在进行进一步的数据分析。该研究中约88%的患者继续进行为期12个月的长期延长研究。pitolisant在成人特发性嗜睡患者中的安全性和耐受性特征与已建立的安全性特征一致，未观察到新的安全性信号。。

Dr. Budur added, 'We are grateful to the patients, family members and clinicians who participated in the INTUNE study. We remain committed to the IH patient community and understand their strong desire for a non-scheduled treatment option for IH. Following a thorough review of the full data set, we will work closely with the FDA to discuss next steps and a path forward for pitolisant in IH.'.

Budur博士补充说：“我们感谢参与INTUNE研究的患者，家属和临床医生。我们仍然致力于IH患者社区，并了解他们对IH的非预定治疗方案的强烈愿望。在对完整数据集进行彻底审查后，我们将与FDA密切合作，讨论IH中pitolisant的后续步骤和前进道路。

Pitolisant is marketed as WAKIX® in the U.S. for the treatment of EDS or cataplexy in adult patients with narcolepsy. Pitolisant is not approved for IH and is currently being evaluated as an investigational agent in adult patients with IH.

Pitolisant在美国作为WAKIX®销售，用于治疗成人发作性睡病患者的EDS或猝倒症。Pitolisant未被批准用于IH，目前正在作为成人IH患者的研究药物进行评估。

Conference Call Today at 8:30 a.m. ETWe are hosting a conference call and webcast today at 8:30 a.m. Eastern Time to discuss the topline data from the Phase 3 INTUNE study. The live and replay webcast of the call will be available on the investor relations page of our website at https://ir.harmonybiosciences.com/.

今天上午8:30的电话会议今天上午8:30召开电话会议和网络广播，讨论第3阶段INTUNE研究的主题数据。该电话的实时和重播网络广播将在我们网站的投资者关系页面上提供https://ir.harmonybiosciences.com/.

To participate in the live call by phone, dial (800) 245-3047 (domestic) or +1 (203) 518-9765 (international), and reference passcode HRMY1013. .

要通过电话进行实时通话，请拨打（800）245-3047（家庭电话）或+1（203）518-9765（国际电话）以及参考密码HRMY1013。

About the INTUNE StudyThe INTUNE study is a placebo-controlled, double-blind, randomized withdrawal Phase 3 registrational trial conducted in adult patients with IH at 52 clinical trial sites across the U.S. A total of 213 patients were enrolled and dosed in the study, of which 139 were randomized. The primary objective was to evaluate the safety and efficacy of pitolisant compared with placebo in treating EDS.

关于INTUNE研究INTUNE研究是一项安慰剂对照，双盲，随机撤药的3期注册试验，在美国52个临床试验点对成人IH患者进行。共有213名患者入选并服用该研究，其中139名为随机分组。主要目的是评估pitolisant与安慰剂治疗EDS的安全性和有效性。

The secondary objectives were to assess the impact of pitolisant on other important symptoms of IH, such as sleep inertia, daytime functioning, and cognitive performance. The INTUNE study had two periods: (1) an 8-week open-label period consisting of 3 weeks of dose titration, 3 weeks of dose optimization and 2 weeks of stable dose; followed by (2) a 4-week double-blind randomized withdrawal (DBRW) period.

次要目标是评估pitolisant对IH其他重要症状的影响，如睡眠惯性，白天功能和认知表现。INTUNE研究有两个阶段：（1）8周的开放标签期，包括3周的剂量滴定，3周的剂量优化和2周的稳定剂量；随后（2）为期4周的双盲随机撤药（DBRW）期。

During the open-label period, all patients were treated with pitolisant. Treatment responders entered the DBRW phase where half of them continued to receive stable dose pitolisant whereas the other half received placebo. All efficacy assessments were administered during the DBRW phase and analyzed to compare the difference between the pitolisant group and the placebo group from the end of stable dose period to the end of the 4-week DBRW phase..

在开放标签期间，所有患者均接受pitolisant治疗。治疗反应者进入DBRW阶段，其中一半继续接受稳定剂量的pitolisant，而另一半接受安慰剂。所有疗效评估均在DBRW阶段进行，并进行分析，以比较从稳定剂量期结束至4周DBRW阶段结束时pitolisant组和安慰剂组之间的差异。。

About Idiopathic HypersomniaIdiopathic Hypersomnia (IH) is a rare and chronic neurological disease that is characterized by excessive daytime sleepiness (EDS) despite sufficient or even long sleep time. 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).

关于特发性嗜睡性嗜睡症（IH）是一种罕见的慢性神经系统疾病，其特征在于尽管有足够或甚至长的睡眠时间，但白天过度嗜睡（EDS）。患有IH的人经历显着的ED以及睡眠惯性（从睡眠中醒来的长期困难）和“脑雾”（认知，注意力和警觉性受损）的症状。

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.

IH的原因尚不清楚，但可能是由于大脑区域的改变稳定了睡眠和觉醒状态。IH是嗜睡的主要疾病之一，与发作性睡病一样，是一种使人衰弱的睡眠障碍，可导致日常功能严重中断。

Approximately 80,000 people in the U.S. are believed to be affected by IH, with 40,000 currently having been diagnosed. IH is a condition with high unmet medical need..

据信美国约有80000人受到IH的影响，目前已诊断出40000人。IH是一种高度未满足医疗需求的疾病。。

About WAKIX® (pitolisant) TabletsWAKIX, 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.

关于WAKIX®（pitolisant）TabletsWAKIX是一种一流的药物，经美国食品和药物管理局批准用于治疗成人发作性睡病患者的过度白天嗜睡或猝倒，自2019年第4季度起在美国上市。2010年获得治疗发作性睡病的孤儿药名称，2018年获得治疗猝倒症的突破性治疗名称。

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).

WAKIX是一种选择性组胺3（H₃) 受体拮抗剂/反向激动剂。WAKIX的作用机制尚不清楚；然而，它的功效可以通过其在H的活性来调节₃ 受体，从而增加组胺（一种促进唤醒的神经递质）的合成和释放。WAKIX由Bioprojet（法国）设计和开发。

Harmony has an exclusive license from Bioprojet to develop, manufacture and commercialize pitolisant in the United States..

Harmony拥有Bioprojet的独家许可，可在美国开发，制造和商业化pitolisant。。

Indications and UsageWAKIX is indicated for the treatment of excessive daytime sleepiness or cataplexy in adult patients with narcolepsy.

适应症和用法Wakix用于治疗成人发作性睡病患者的白天过度嗜睡或猝倒。

Important Safety Information

重要的安全信息

ContraindicationsWAKIX 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.

禁忌症对于已知对pitolisant或制剂任何成分过敏的患者禁用Wakix。有报道过敏反应。WAKIX也禁用于严重肝功能损害的患者。

Warnings and PrecautionsWAKIX 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..

警告和注意事项Wakix延长QT间隔；避免在已知QT延长的患者中使用WAKIX或与已知延长QT间期的其他药物联合使用。避免用于有心律失常病史的患者，以及其他可能增加尖端扭转型室速或猝死发生风险的情况，包括症状性心动过缓，低钾血症或低镁血症，以及先天性延长QT间期。。

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).

由于较高浓度的pitolisant，肝或肾功能损害患者QT间期延长的风险可能更大；监测这些患者的QTc升高。对于中度肝功能损害和中度或重度肾功能损害的患者，建议进行剂量调整（参见完整的处方信息）。

WAKIX is not recommended in patients with end-stage renal disease (ESRD)..

WAKIX不推荐用于终末期肾病（ESRD）患者。。

Adverse ReactionsIn 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..

不良反应在有或没有猝倒症的发作性睡病患者中进行的安慰剂对照临床试验中，WAKIX最常见的不良反应（≥5%和至少两次安慰剂）是失眠（6%），恶心（6%）和焦虑（5%）。其他不良反应发生率≥2%，比安慰剂治疗组更频繁，包括头痛，上呼吸道感染，肌肉骨骼疼痛，心率增加，幻觉，烦躁不安，腹痛，睡眠障碍，食欲减退，瘫痪，口干，和皮疹。。

Drug InteractionsConcomitant administration of WAKIX with strong CYP2D6 inhibitors increases pitolisant exposure by 2.2-fold. Reduce the dose of WAKIX by half.

药物相互作用同时给予WAKIX与强CYP2D6抑制剂使pitolisant暴露增加2.2倍。将WAKIX的剂量减少一半。

Concomitant use of WAKIX with strong CYP3A4 inducers decreases exposure of pitolisant by 50%. Dosage adjustments may be required (see full prescribing information).

与强CYP3A4诱导剂同时使用WAKIX可使pitolisant的暴露减少50%。可能需要调整剂量（请参阅完整的处方信息）。

H1 receptor antagonists that cross the blood-brain barrier may reduce the effectiveness of WAKIX. Patients should avoid centrally acting H1 receptor antagonists.

穿过血脑屏障的H1受体拮抗剂可能会降低WAKIX的有效性。患者应避免中枢作用的H1受体拮抗剂。

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..

WAKIX是CYP3A4的临界/弱诱导剂。因此，当与WAKIX同时使用时，可能会降低敏感CYP3A4底物的有效性。与WAKIX一起使用时，激素避孕药的有效性可能会降低，并且在停药后21天内有效性可能会降低。。

Use in Specific PopulationsWAKIX 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.

在特定人群中使用wAkix可能会降低激素避孕药的有效性。应建议使用激素避孕药的患者在使用WAKIX治疗期间和停药后至少21天内使用替代性非激素避孕药。

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.

有一个妊娠暴露登记处监测怀孕期间接触过WAKIX的妇女的妊娠结局。如果患者怀孕，应鼓励患者参加WAKIX妊娠注册。要注册或从注册表中获取信息，患者可以致电1-800-833-7460。

The safety and effectiveness of WAKIX have not been established in patients less than 18 years of age..

WAKIX的安全性和有效性尚未在18岁以下的患者中确定。。

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被肝脏广泛代谢。WAKIX禁用于严重肝功能损害患者。中度肝功能损害患者需要调整剂量。

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.

WAKIX不推荐用于终末期肾病患者。对于中度或重度肾功能不全患者，建议调整WAKIX的剂量。

Dosage reduction is recommended in patients known to be poor CYP2D6 metabolizers; these patients have higher concentrations of WAKIX than normal CYP2D6 metabolizers.

对于已知CYP2D6代谢不良的患者，建议减少剂量；这些患者的WAKIX浓度高于正常的CYP2D6代谢者。

Please see the Full Prescribing Information for WAKIX for more information.

有关更多信息，请参阅WAKIX的完整处方信息。

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.

要报告疑似不良反应，请致电1-800-833-7460联系Harmony Biosciences或致电1-800-FDA-1088或www.FDA.gov/medwatch联系FDA。

About Harmony BiosciencesAt 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.

关于和谐生物科学在和谐生物科学领域，我们专注于开发和提供其他人经常忽视的罕见神经系统疾病的治疗方法。我们相信，在同理心和创新相遇的地方，神经疾病患者可以开始更好的生活。由Paragon Biosciences，LLC于2017年成立，总部设在宾夕法尼亚州普利茅斯会议，我们来自各种学科和经验的专家团队得益于我们共同的信念，即创新科学转化为患者的治疗可能性，我们所做的一切的核心。

For more information, please visit www.harmonybiosciences.com..

欲了解更多信息，请访问www.harmonybiosciences.com。。

Forward Looking StatementThis 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 product WAKIX.

前瞻性声明本新闻稿包含1995年“私人证券诉讼改革法”含义内的前瞻性声明。本新闻稿中包含的与历史事实无关的所有声明均应视为前瞻性声明，包括有关我们产品WAKIX的声明。

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 WAKIX, 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 development activities with Bioprojet, and plans to explore the therapeutic potential of pitolisant in additional indications; our ongoing and planned clinical trials; 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 of our product candidates, including those we are developing with Bioprojet; our failure to achieve the potential benefits of the 2022 LCA with Bioprojet; our estimates regarding expenses, future revenue, capital requirements and needs for additional financing; our ability to identify additional products or product candidates with significant commercial potential that are consistent with our commercial object.

这些陈述既不是承诺也不是保证，但涉及已知和未知的风险，不确定性和其他重要因素，这些因素可能导致我们的实际结果，绩效或成就与前瞻性表达或暗示的任何未来结果，绩效或成就有实质性差异。声明，包括但不限于，以下内容：我们WAKIX的商业化努力和战略；WAKIX，pitolisant在其他适应症中的市场接受率和临床应用程度（如果批准）以及我们可能开发或获取的任何其他候选产品（如果批准）；我们的研究和开发计划，包括我们与Bioprojet的开发活动，以及探索pitolisant在其他适应症中的治疗潜力的计划；我们正在进行和计划中的临床试验；WAKIX提供有利的保险和报销；对于其他适应症以及我们的任何候选产品，包括我们正在使用Bioprojet开发的产品，pitolisant的时间安排和我们获得监管批准的能力；我们未能通过Bioprojet实现2022 LCA的潜在好处；我们对费用，未来收入，资本要求和额外融资需求的估算；我们能够识别与我们的商业目标一致的具有显着商业潜力的其他产品或候选产品。

Harmony Biosciences Media Contact:Cate McCanless202-641-6086[email protected]

Harmony Biosciences Media联系人：Cate McCanless202-641-6086[电子邮件保护]

Harmony Biosciences Investor Contact:Luis Sanay, CFA445-235-8386[email protected]

Harmony Biosciences投资者联系人：Luis Sanay，CFA445-235-8386[电子邮件保护]

SOURCE Harmony Biosciences

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