PLYMOUTH MEETING, Pa., Oct. 5, 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 the presentation of new secondary endpoint data, including improvements in behavioral disturbances, from its Phase 2 signal-detection study evaluating pitolisant for the treatment of excessive daytime sleepiness (EDS) in Prader-Willi syndrome (PWS), at the 2023 Foundation for Prader-Willi Research (FPWR) Symposium and Family Conference.

宾夕法尼亚州普利茅斯会议，2023年10月5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，今天宣布提供新的次要终点数据，包括改善行为障碍，在2023年Prader-Willi研究基金会（FPWR）研讨会和家庭会议上，评估pitolisant治疗Prader-Willi综合征（PWS）过度白天嗜睡（EDS）的2期信号检测研究。

The company also announced that it anticipates initiating its Phase 3 registrational TEMPO study in Q4 2023..

该公司还宣布预计将于2023年第四季度启动第三阶段注册TEMPO研究。。

The poster presentation of secondary outcomes data included improvements in behavioral symptoms (as measured by the Aberrant Behavioral Checklist-2), especially in the higher-dose pitolisant group. Reductions in the caregiver rating of EDS severity were also observed as were some improvements in hyperphagia, even though baseline hyperphagia scores were in the normal to mild range.

次要结果数据的海报展示包括行为症状的改善（通过异常行为检查表-2测量），特别是在高剂量pitolisant组中。即使基线食欲亢进评分在正常至轻度范围内，也观察到EDS严重程度的护理人员评分降低，食欲亢进也有所改善。

The overall rate of adverse events was similar for pitolisant and placebo, and the safety/tolerability profile was consistent with the known profile for pitolisant..

pitolisant和安慰剂的总体不良事件发生率相似，安全性/耐受性概况与pitolisant的已知概况一致。。

'We recognize the urgency for innovative treatments that help alleviate the profound unmet medical needs of individuals with PWS and their dedicated caregivers,' said Kumar Budur, MD, Chief Medical Officer at Harmony Biosciences. 'This is particularly crucial given the absence of an FDA-approved treatment for EDS in PWS, coupled with the prevalent and severe behavioral symptoms associated with this condition.

“我们认识到创新治疗的紧迫性，这些治疗有助于缓解PWS患者及其专职护理人员的深远未满足的医疗需求，”Harmony Biosciences首席医疗官Kumar Budur博士说鉴于PWS中没有FDA批准的EDS治疗方法，以及与这种情况相关的普遍和严重的行为症状，这一点尤其重要。

We are encouraged by these findings from our Phase 2 signal-detection study, which build upon the favorable primary study outcome and provide additional hope to this community as we pursue a potential new indication for pitolisant.'.

我们对第二阶段信号检测研究的这些发现感到鼓舞，这些研究建立在有利的初步研究结果的基础上，并为我们寻求潜在的pitolisant新适应症时为这个社区提供了额外的希望。

The results from the Phase 2 signal-detection study informed the protocol design for the upcoming Phase 3 registrational TEMPO study, a randomized, double-blind, placebo-controlled, multicenter, global clinical study that will further assess the safety and efficacy of pitolisant in patients with PWS, ages ≥ 6 years.

第2阶段信号检测研究的结果为即将进行的第3阶段注册TEMPO研究提供了方案设计，这是一项随机，双盲，安慰剂对照，多中心，全球临床研究，将进一步评估pitolisant的安全性和有效性。PWS患者，年龄≥6岁。

This study is expected to be initiated in Q4 2023. There are currently 15,000 – 20,000 people in the US living with PWS. More than half of them experience EDS and the majority of them have behavioral disturbances..

这项研究预计将于2023季度启动。目前，美国有15000–20000人患有PWS。他们中有一半以上经历过ED，而大多数人都有行为障碍。。

Poster: Secondary Outcomes from a Phase 2, Double-Blind, Placebo-Controlled Signal-Detection, Proof-of-Concept Study of Pitolisant in Prader-Willi Syndrome

海报：第二阶段，双盲，安慰剂对照信号检测的次要结果，Prader-Willi综合征中Pitolisant的概念验证研究

The Phase 2 clinical trial was a randomized, double-blind, placebo-controlled signal-detection, proof-of-concept study designed to assess the safety and efficacy of pitolisant in people living with PWS. In the trial, eligible patients who were genetically confirmed to have PWS and who had EDS were enrolled in an 11-week double-blind treatment phase that included a 3-week titration phase and eight weeks of stable dosing.

2期临床试验是一项随机，双盲，安慰剂对照的信号检测，概念验证研究，旨在评估pitolisant在PWS患者中的安全性和有效性。在该试验中，经过基因证实具有PWS和EDS的合格患者参加了为期11周的双盲治疗阶段，其中包括3周的滴定阶段和8周的稳定给药。

Participants (n=65) were randomized (1:1:1) to receive lower- or higher-dose pitolisant, or a matching placebo based on age. Secondary/exploratory endpoints included change from baseline in Caregiver Global Impression of Severity (CaGI-S) for EDS; behavioral disturbance, as measured using the Aberrant Behavior Checklist-2 (ABC-2); and Hyperphagia, assessed using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) in conjunction with the Food Safe Zone Questionnaire..

参与者（n=65）随机（1:1:1）接受低剂量或高剂量的pitolisant，或基于年龄的匹配安慰剂。次要/探索性终点包括护理人员总体严重程度印象（CaGI-S）与基线的变化；使用异常行为检查表-2（ABC-2）测量的行为障碍；和食欲亢进，使用临床试验食欲亢进问卷（HQ-CT）结合食品安全区问卷进行评估。。

This proof-of-concept study was not powered to demonstrate statistical significance and was designed for signal detection.

这种概念验证研究无法证明统计显着性，而是设计用于信号检测。

Key results include:

主要成果包括：

Reductions in behavioral disturbances among the youngest age group (6 to <12 years) were observed across all ABC-2 domains especially in the higher-dose pitolisant group.

在所有ABC-2结构域中观察到最年轻年龄组（6至<12岁）的行为障碍减少，特别是在高剂量pitolisant组中。

Irritability: higher-dose, -5.5; lower-dose, -3.0; placebo, -1.5Social withdrawal: higher-dose, -4.9; lower-dose, -1.6; placebo, -3.1Hyperactivity/noncompliance: higher-dose, -4.6; lower-dose, -0.9; placebo, -3.0Inappropriate speech: higher-dose, -2.0; lower-dose, -0.4; placebo, -0.6Stereotypic behavior: higher-dose, -1.0; lower-dose, -0.2; placebo, -0.6.

易怒：剂量较高，-5.5；较低剂量，-3.0；安慰剂，-1.5社交退缩：较高剂量，-4.9；较低剂量，-1.6；安慰剂，-3.1活动过度/不依从性：较高剂量，-4.6；较低剂量，-0.9；安慰剂，-3.0不恰当的言论：更高的剂量，-2.0；较低剂量，-0.4；安慰剂，-0.6定型行为：较高剂量，-1.0；较低剂量，-0.2；安慰剂，-0.6。

Reductions in CaGI-S scores were greater for pitolisant compared with placebo in the children (higher-dose, -1.1; lower-dose, -1.0; placebo, -0.5) and adult (higher-dose, -1.0; lower-dose, -2.0; placebo, -0.7) age groups.

儿童（高剂量，-1.1；低剂量，-1.0；安慰剂，-0.5）和成人（高剂量，-1.0；低剂量，-2.0；安慰剂）与安慰剂相比，pitolisant的CaGI-S评分降低更大，-0.7）年龄组。

A reduction of -1.0 or more was seen in the mean change from baseline to week 11 in the children and adult subgroups, meeting the clinical significance threshold per The American Academy of Sleep Medicine (AASM).

儿童和成人亚组从基线到第11周的平均变化减少了-1.0或更多，达到了美国睡眠医学学会（AASM）的临床意义阈值。

Some improvements in hyperphagia were noted in children (higher-dose, -2.0; lower-dose, -2.5; placebo, 0.1) and adults (higher-dose, -3.4; lower-dose, -3.0; placebo, -1.7) even though baseline hyperphagia scores were in the normal/mild range.

尽管基线食欲亢进评分，儿童（高剂量，-2.0；低剂量，-2.5；安慰剂，0.1）和成人（高剂量，-3.4；低剂量，-3.0；安慰剂，-1.7）在正常/轻度范围内。

Despite the trial not enriching for hyperphagia and HQ-CT scores being relatively low at baseline, encouraging trends toward improvements were seen compared with placebo, especially in the children age group.

尽管试验没有丰富食欲亢进，HQ-CT评分在基线时相对较低，但与安慰剂相比，尤其是在儿童年龄组中，出现了令人鼓舞的改善趋势。

There was an unusually large placebo response in the adolescent age group, due to data from a single outlier, resulting in an outsized impact on the magnitude of the placebo response not only in the adolescent age group but also in the overall study population.

由于来自单个异常值的数据，在青少年年龄组中存在异常大的安慰剂反应，导致不仅在青少年年龄组中而且在整个研究人群中对安慰剂反应的幅度的巨大影响。

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.

Pitolisant在美国以WAKIX®销售，并获得FDA批准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PWS患者，目前正在评估该患者群体中的研究药物。

About Prader-Willi SyndromePWS 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).

关于Prader-Willi综合征PWS是一种孤儿/罕见的遗传性神经系统疾病，其许多症状是由下丘脑功能障碍引起的。下丘脑是控制睡眠-觉醒状态稳定性和调节饥饿感与饱腹感之间平衡的信号的大脑部分，导致PWS患者的两个主要症状，EDS和食欲亢进（强烈的持续饥饿感，伴随着食物的关注，极端的食物消费驱动力，与食物有关的行为问题以及缺乏正常的饱腹感）。

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 and the majority of them have behavioral disturbances..

其他功能包括低肌张力，身材矮小，行为问题和认知障碍。美国约有15000至20000人患有PWS，其中一半以上患有ED，其中大多数患有行为障碍。。

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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