Tic Disorders

Phase 2b study will evaluate the safety and efficacy of gemlapodect (NOE-105) in patients with Tourette syndromeBASEL, Switzerland, Oct. 30, 2024 (GLOBE NEWSWIRE) -- Noema Pharma AG, a clinical-stage neuroscience-based company, today announced the first patients have been dosed in a global Phase 2b study evaluating the safety and efficacy of gemlapodect (NOE-105) in Tourette syndrome. NOE-TTS-201 (NCT06315751) is a Phase 2b, 12-week, randomized, double-blind, placebo-controlled study that is designed to examine the safety and efficacy of gemlapodect. The trial will enroll 140 patients with Tourette syndrome in multiple centers in the US and Europe. Patients will be treated with up to 15 mg of gemlapodect once daily, or a matching placebo. The primary endpoint is the Yale Global Tic Severity Scale (YGTSS) Total Tic Score. “Patients with Tourette syndrome carry an incredible burden related to the expression of motor and vocal tics with limited treatment options,” said Ilise Lombardo, M.D., Chief Executive Officer of Noema Pharma. “I am happy to announce the progression of the development of gemlapodect in Tourette syndrome with the dosing of the first patients in our Phase 2b trial.” About Tourette Syndrome Tourette syndrome is a neurodevelopmental disorder in the wider spectrum of tic disorders, consisting of motor and vocal abrupt and brief movement or sound which is preceded by a local or generalized urge/premonitory sensation. TS impacts over a half-million individuals and families in the US alone, as well as millions of individuals worldwide. About NOE-105/gemlapodect NOE-105/gemlapodect is a potential first-in-class phosphodiesterase-10A (PDE10A) inhibitor in mid-stage clinical development as a dopamine modulator for Tourette syndrome. NOE-105 has been well-tolerated in studies with healthy volunteers and in patients with Tourette syndrome. NOE-105 has the potential to achieve a more targeted effect by modulating dopamine signaling exclusively in the medium spiny neurons of the striatum in the brain, while limiting off-target effects compared to other dopamine antagonists. About Noema Pharma Noema Pharma is a clinical-stage biotech company advancing a portfolio of transformative therapeutics utilizing first-in-disease approaches targeting neuroscience-based conditions with high unmet need. Noema has four programs currently in active Phase 2 clinical trials evaluating pain in Trigeminal Neuralgia, seizures in Tuberous Sclerosis Complex, Tourette syndrome and vasomotor symptoms plus associated symptoms of menopause with readouts expected in 2025. Noema was founded by leading venture capital firm Sofinnova Partners and is supported by current investors including Forbion, Gilde Healthcare, Invus, Jeito Capital, Polaris Partners and UPMC Enterprises. Learn more at www.noemapharma.com. Investor Contact: Precision AQAlex Lobo212-698-8802alex.lobo@precisionaq.com

杭州的秋天属于桂花香，馥郁的香气飘散在整座城市。然而，虽然眼下桂花飘香，但对不少人而言，不仅快乐不起来，更是噩梦一般的存在。 “桂花开了以后门诊数量急剧上升”，杭州市中医院耳鼻喉科梅显伟副主任医师表示，半天门诊看了40位患者，一半以上为过敏性鼻炎，多是因为花粉过敏，以中青年居多。 过敏性鼻炎也称为变应性鼻炎（AR），是临床常见的慢性鼻病，因特应性个体暴露于过敏原（变应原）后主要由免疫球蛋白E（IgE）介导的鼻黏膜非感染性慢性炎性疾病，已成为主要的呼吸道慢性炎性疾病，影响着全世界10%～20%的人口。 AR 的发病与环境因素直接相关，不同地区的过敏原也有所不同。北京地区儿童常见吸入过敏原为尘螨、真菌、杂草花粉和动物毛等；西北和东北地区主要过敏原为杂草花粉；华东、华中 和 华 南地 区 过 敏 原 以 粉 尘 螨 和 屋 尘 螨 为主。近年来，饲养宠物导致儿童对猫毛和狗毛过敏以及某些食物过敏原与花粉过敏原之间存在交叉抗原性的问题也受到关注。AR 的遗传特征较为明显，父母罹患变应性疾病会增加儿童AR的发病风险。    临床分类 1、按过敏原种类分类 ①季节性AR：常见过敏原为花粉、真菌等季节性吸入过敏原。 ②常年性AR：常见过敏原为尘螨、蟑螂、动物皮屑等室内常年性吸入过敏原，以及某些职业性过敏原。 2、按症状发作时间分类 ①间歇性AR：症状发作＜4d/周，或＜连续4周。 ②持续性AR：症状发作≥4d/周，且≥连续4周。 3、按疾病严重程度程度分类 ①轻度AR：症状轻微，对生活质量（包括睡眠、日常生活、工作学习）未产生明显影响。 ②中-重度AR：症状较重或严重，对生活质量产生明显影响。 临床表现 1、症状  AR的典型症状为阵发性喷嚏、清水样涕、鼻痒和鼻塞；可伴有眼部症状，包括眼痒、流泪、眼红和灼热感等，多见于花粉过敏患者。随着致敏花粉飘散季节的到来，花粉症患者的鼻、眼症状发作或加重。如果致病因素以室内过敏原（尘螨、蟑螂、动物皮屑等）为主，症状多为常年发作。 40%的AR患者可合并支气管哮喘，在有鼻部症状的同时还可伴喘鸣、咳嗽、气急、胸闷等肺部症状。 2、体征 AR发作时最主要的体征是双侧鼻黏膜苍白、肿胀，下鼻甲水肿，鼻腔有多量水样分泌物。眼部体征主要为结膜充血、水肿，有时可见乳头样反应。伴有哮喘、湿疹或特应性皮炎的患者有相应的肺部、皮肤体征。    临床诊断 ①症状：阵发性喷嚏、清水样涕、鼻痒和鼻塞等症状出现2个或以上，每天症状持续或累计在1h以上，可伴有流泪、眼痒和眼红等眼部症状； ②体征：常见鼻黏膜苍白、水肿，鼻腔水样分泌物； ③过敏原检测：至少1种过敏原SPT和/或血清特异性IgE阳性，或鼻激发试验阳性。AR的诊断应根据患者典型的过敏病史、临床表现以及与其一致的过敏原检测结果而作出。 过敏原检测通常需要将体内和体外检测相结合，且充分结合临床病史，以判断患者是由何种过敏原致敏，以及致敏的程度与疾病症状的关系。 鉴别诊断 1、急性鼻炎：亦称普通感冒，早期可有喷嚏、鼻塞、清水样涕等症状，流感引发的急性鼻炎多突然起病，常有咳嗽、流涕或鼻塞症状，其主要症状为发热，体温可达39～40℃，伴头痛、肌肉酸痛、乏力等全身症状。 2、非变应性鼻炎伴嗜酸粒细胞增多综合征：该病临床表现与AR难以区分，但症状较重，可伴嗅觉减退。其主要特征是高倍镜下鼻分泌物嗜酸粒细胞占比>20%，伴外周血嗜酸粒细胞增多，过敏原检测为阴性。 3、血管运动性鼻炎：其症状与儿童 AR 相似，主要包括鼻塞及清水样涕，少数患者亦有喷嚏及鼻痒。诱发因素包括温度湿度变化、刺激性气味及运动等。鼻腔检查鼻黏膜一般可呈充血或苍白，外周血和鼻分泌物嗜酸粒细胞数量正常，过敏原检测为阴性。 4、鼻窦炎：鼻窦炎可与 AR 有相似的症状，如鼻塞、流涕、咳嗽、头痛、嗅觉减退等，两者也可能合并存在。但鼻窦炎患儿鼻腔分泌物通常为黏脓性，可伴面部疼痛或压痛。鼻内镜检查及必要时的鼻窦CT检查有助于鼻窦炎的诊断。    5、脑脊液鼻漏：儿童脑脊液鼻漏多为先天性，临床症状多表现为单侧清水样涕，量可因头位变化而改变。鼻漏出液的糖定量或 β2 转铁蛋白检查有助于鉴别，必要时鼻内镜或影像学检查可帮助识别漏口位置。 6、抽动障碍：指突然、无目的、快速、刻板的肌肉收缩，临床症状多样，可表现为皱鼻、吸气、眨眼等，与部分AR患儿症状相似。抽动症状不由某些物质、药物或其他医疗事件引起，鼻腔检查及过敏原检测均为阴性。 7、其他疾病：儿童先天性后鼻孔闭锁、鼻腔狭窄、鼻腔异物、鼻中隔偏曲和腺样体肥大等疾病可引起鼻塞症状，也需要与AR进行鉴别。 治疗 AR的治疗原则为“防治结合，四位一体”，包括环境控制、药物治疗、免疫治疗和健康教育。 1、环境控制 避免或尽可能减少接触相关过敏原。以花粉为例，一天中花粉漂浮相对密集时间是 14∶ 00 ～16∶ 00，有些植物在 20∶ 00 ～ 22∶ 00 还会形成第 2 次花粉漂浮高峰。因此，尽量在花粉漂浮高峰时段减少外出，关闭门窗以避免或减少花粉进入室内。 2、药物治疗  AR常用治疗药物分为一线用药和二线用药。一线治疗药物包括鼻用糖皮质激素（简称鼻用激素）、第二代口服和鼻用抗组胺药、口服白三烯受体拮抗剂；二线治疗药物包括口服糖皮质激素、口服和鼻用肥大细胞膜稳定剂、鼻用减充血剂、鼻用抗胆碱能药。    其中，鼻用糖皮质激素可在鼻腔局部发挥抗炎、抗过敏和抗水肿特性，并具有免疫抑制作用，是变应性鼻炎治疗中最重要的一线用药。 第二代鼻用激素——丙酸氟替卡松，具有强效局部抗炎与抗过敏作用，可减轻鼻腔炎症水肿、渗出与毛细血管扩张，有效控制患者鼻痒、鼻塞与流涕等变应性症状；采用鼻腔局部给药，可显著提升鼻黏膜吸收率，药物浓度较高，起效较快，且安全性较高。 3、免疫治疗 免疫治疗是AR的一线治疗方法，目前临床常用的免疫治疗方法有皮下注射法（皮下免疫治疗）和舌下含服法（舌下免疫治疗），分为剂量递增和剂量维持两个阶段，总疗程为3年。 皮下免疫治疗通常在5岁以上的患者中开展，舌下免疫治疗可以放宽到3岁，具体需遵循药品说明书中的年龄规定。 （1）适应证：免疫治疗适用于过敏原特异性IgE介导的疾病，包括AR、变应性结膜炎和变应性哮喘。根据临床症状、体征、SPT和/或血清特异性IgE检测结果阳性确诊疾病者，适宜进行免疫治疗，在疾病初期即可开展，无需以药物治疗失败为前提。    免疫治疗尤其适用于以下患者： ①用常规药物治疗和过敏原回避等措施不能有效控制症状者； ②需要大剂量药物和/或多种药物联合使用方能控制症状者； ③药物治疗引起不良反应者； ④希望避免长期使用药物者； ⑤希望预防AR或哮喘发病者。 对出现严重不良反应、无法频繁至医院等不能进行皮下免疫治疗的患者，可考虑舌下免疫治疗。 （2）禁忌证：包括绝对禁忌证和相对禁忌证。 绝对禁忌证包括： ①未控制的或重症哮喘［第一秒用力呼气容积（FEV1）＜70%预计值］和不可逆的呼吸道阻塞性病变； ②免疫性疾病活动期； ③恶性肿瘤。 相对禁忌证包括： ①哮喘得到部分控制； ②正在使用β受体阻滞剂或血管紧张素酶抑制剂； ③严重的心血管系统疾病，发生严重不良反应时可能增加使用肾上腺素的风险； ④自身免疫性疾病缓解期； ⑤严重的精神系统疾病或依从性差（包括不能理解治疗的风险和局限性）、经常不能按时返院就诊者； ⑥原发性或继发性免疫缺陷；    ⑦免疫治疗过程中曾发生过严重不良反应； ⑧不推荐在妊娠期或计划妊娠期开始免疫治疗，在维持治疗阶段出现妊娠的，应充分告知患者风险并征得同意，再决定是否继续治疗，发生不良反应时应终止免疫治疗；⑨几种特殊情况：花粉过敏引起的季节性AR患者在花粉播散期禁止开始免疫治疗；急性感染、发热或接种其他疫苗（如新型冠状病毒疫苗）等情况下，应推迟或暂停免疫治疗，必要时调整剂量；皮下免疫治疗注射治疗当天应避免剧烈运动和饮酒，口腔溃疡或外伤时不应给予舌下免疫治疗。相对禁忌证在评估获益大于风险时可以谨慎使用，在治疗期间应严密观测。 （3）皮下免疫治疗  根据剂量累加阶段注射频率的不同，皮下免疫治疗可分为常规免疫治疗和加速免疫治疗，后者又可分为集群免疫治疗和冲击免疫治疗。目前国内临床应用较多的是常规免疫治疗和集群免疫治疗。 出现下列情况之一时，应考虑推迟免疫治疗： ①1周内有发热或急性呼吸道感染病史； ②近期肺功能显著下降； ③注射前有过敏反应发作； ④特应性皮炎或湿疹发作期； ⑤最近接触过较多过敏原； ⑥1周内注射了其他疫苗； ⑦正在使用β受体阻滞剂或血管紧张素酶抑制剂； ⑧3～4 d内有全身性的并发疾病及哮喘发作。 不良反应：     （4）舌下免疫治疗 国内目前可供临床使用的舌下含服标准化过敏原疫苗有粉尘螨滴剂和黄花蒿花粉滴剂。与皮下免疫治疗相比，舌下免疫治疗操作相对简便，具有无创性、耐受性和安全性好等特点，但需要每天给药，治疗的依从性有待通过患者教育等各种策略进行提高。 来源 | 中国变应性鼻炎诊断和治疗指南（2022版） 撰文｜Anna.AN 编辑 | Swagpp ● 哀悼！近期两名顶级科主任突然离世！享年均为59岁！15岁考上大学、天才医生、风湿免疫专家、糖尿病防治大咖！我们无比惋惜悲痛 ● 每一口外卖、瓶装水都影响生殖健康！柳叶刀子刊：微塑料恐侵入并损伤男性生殖系统，尤其是不粘锅涂层 ● 震撼！超百家医院、诊所、药店主动退出医保！国家医保局通报无锡骗保案，举报有奖！“上网比药价”实施，留给药店的时间不多了 版权说明：梅斯医学（MedSci）是国内领先的医学科研与学术服务平台，致力于医疗质量的改进，为临床实践提供智慧、精准的决策支持，让医生与患者受益。欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。 点击下方「阅读原文」 立刻下载梅斯医学APP！

– Topline results from Phase 2a study – Nearly 60% of all patients treated with gemlapodect and 88% of patients completing the study at the target clinical dose range were responders based on the primary efficacy assessment The Yale Global Tics Severity Scale Total Tic Score (YGTSS-TTS) showed a statistically significant improvement of -7.8 points for all patients, and -12.8 points for patients completing the study at the target clinical dose No weight gain, events of metabolic marker increase, or serious adverse events were reported BASEL, Switzerland, Oct. 17, 2024 (GLOBE NEWSWIRE) -- Noema Pharma AG, a clinical-stage neuroscience-based company, today announced the Phase 2a ALLEVIA-1 study with NOE-105 (gemlapodect) in patients with Tourette syndrome (TS) met its primary and all key secondary endpoints. Gemlapodect is a novel and first-in-class PDE10A inhibitor currently being studied to assess its potential to reduce vocal and motor tics in people with TS with an improved tolerability profile over current treatment options. The Phase 2a study, ALLEVIA-1 (NOE-TTS-211), was a multicenter, 12-week, open-label, single-arm monotherapy study which enrolled a total of 15 patients with TS with a mean age of 26.2 (+/- 8.7) years. Patients were treated with ascending doses of gemlapodect ranging from 2.5 to 15 mg once daily, with a target dose range of 10 to 15 mg per day. The ALLEVIA-1 study achieved its primary and secondary objectives. Key findings included: 57% of patients showed tic improvement compared to baseline, with the remaining patients having no change and no patients worsening on the independently adjudicated TS Clinical Global Impression of Change (TS-CGI-C; primary endpoint) (n=14 patients taking at least one dose of study medication and having at least one post-baseline efficacy assessment).For patients who completed the study within the target clinical dose range, 87.5% showed improvement and 75% were rated as much or very much improved on the TS-CGI-C (n=8).YGTSS Total Tic Score showed a mean improvement of -7.8 points (p=0.009) from baseline to endpoint for all patients taking at least one dose and having at least one post-baseline assessment.YGTSS Total Tic Score showed a mean improvement of -12.8 points (p=0.003) from baseline to endpoint for all patients completing the study within the target clinical dose range.Adverse events were consistent with the known profile of gemlapodect, and no serious adverse events were reported during the trial.No weight gain and no clinically significant changes in laboratories (including metabolic measures such as blood glucose or lipids) were reported. “Based on these promising data, we believe gemlapodect has the potential to offer a meaningful advancement in the treatment of Tourette syndrome,” said Ilise Lombardo M.D., CEO of Noema Pharma. “I would like to thank the investigators and patients for their important contributions to the ALLEVIA-1 study.” “Tourette syndrome is a devastating disease that impacts patients and their families. Recurrent and severe tics interfere with the patient’s ability to learn, work and interact with others.” said Prof. Kirsten Mueller-Vahl, Principal Investigator, MHH, Hannover, Germany. “Current treatments, essentially antipsychotics, are associated with side effects such as significant weight gain and insulin resistance, as well as stigma. Our findings with gemlapodect are very encouraging, given that the need for new treatments and novel mechanisms in Tourette syndrome remains notably high.” Initial study data were presented at the MDS 2024 Congress, September 28, 2024. About Noema Pharma Noema Pharma is a clinical-stage biotech company advancing a portfolio of transformative therapeutics utilizing first-in-disease approaches targeting neuroscience-based conditions with high unmet need. Noema has four programs currently in active Phase 2 clinical trials evaluating pain in Trigeminal Neuralgia, seizures in Tuberous Sclerosis Complex, Tourette syndrome and vasomotor symptoms plus associated symptoms of menopause with readouts expected in 2025. Noema was founded by leading venture capital firm Sofinnova Partners and is supported by current investors including Forbion, Gilde Healthcare, Invus, Jeito Capital, Polaris Partners and UPMC Enterprises. Learn more at www.noemapharma.com. About NOE-105/gemlapodect NOE-105/gemlapodect is a potential first-in-class phosphodiesterase-10A (PDE10A) inhibitor in mid-stage clinical development as a dopamine modulator for Tourette syndrome. NOE-105 has been well-tolerated in studies with healthy volunteers and in patients with Tourette syndrome with no evidence of metabolic side effects including weight gain, hyperlipidemia and type 2 diabetes. NOE-105 has the potential to achieve a more targeted effect by modulating dopamine signaling exclusively in the medium spiny neurons of the striatum in the brain, while limiting off-target effects compared to other dopamine antagonists. About Tourette Syndrome Tourette syndrome is a neurodevelopmental disorder in the wider spectrum of tic disorders, consisting of motor and vocal abrupt and brief movement or sound which is preceded by a local or generalized urge/premonitory sensation. TS impacts over a half-million individuals and families in the US alone, as well as millions of individuals worldwide. Investors Contact and Media Contact Precision AQAlex Lobo212-698-8802alex.lobo@precisionaq.com