An Open-label, 2 Part, Study to Assess the Pharmacokinetics of a Spray Dried Dispersion Formulation of Radiprodil Under Fasted and Fed Conditions in Healthy Adult Subjects: Part B

开始日期2025-01-16

申办/合作机构

GRIN Therapeutics, Inc.

[+1]

ACTRN12624001366549 / Not yet recruiting临床1期

An Open-label, 2 Part, Study to Assess the Pharmacokinetics of a Spray Dried Dispersion Formulation of Radiprodil Under Fasted and Fed Conditions in Healthy Adult Subjects: Part A

开始日期2024-11-18

申办/合作机构

GRIN Therapeutics, Inc.

[+1]

NCT06392009 / Recruiting临床1/2期

A Multicenter, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Effect on Seizures and Behavioral Symptoms of Radiprodil in Patients with Tuberous Sclerosis Complex (TSC) or Focal Cortical Dysplasia (FCD) Type II

Study RAD-GRIN-201 is a phase 1B/2A trial to assess safety, tolerability, pharmacokinetics (PK), and potential efficacy of radiprodil in participants with Tuberous Sclerosis Complex (TSC) or Focal Cortical Dysplasia (FCD) type II. The study is open-label, so all participants will be treated with radiprodil. Subjects' participation in the study is expected to last up to six months in Part A and one year in Part B/long-term treatment period. The treatment period in Part B may be extended based on a favorable benefit/risk profile.

开始日期2024-07-10

申办/合作机构

GRIN Therapeutics, Inc.

100 项与 Radiprodil 相关的临床结果

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100 项与 Radiprodil 相关的转化医学

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100 项与 Radiprodil 相关的专利（医药）

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项与 Radiprodil 相关的文献（医药）

2024-10-01·EPILEPSIA

Progress report on new medications for seizures and epilepsy: A summary of the 17th Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVII). II. Drugs in more advanced clinical development

Article

作者: White, H. Steve ; Johannessen, Svein I. ; Perucca, Emilio ; Tomson, Torbjörn ; Koepp, Matthias J. ; Bialer, Meir ; Perucca, Piero

Abstract:

The 17th Eilat Conference on New Antiepileptic Drugs and Devices took place in Madrid, Spain on May 5–8, 2024. As usual, the core part of the conference consisted of presentations on investigational drugs at various stages of development for epilepsy‐related indications. Summaries of information on compounds in preclinical or early clinical development are included in an accompanying publication (Part I). In this article, we provide summaries for five compounds in more advanced clinical development, i.e. compounds for which some information on antiseizure activity in individuals with epilepsy is available. These investigational treatments include azetukalner (XEN1101), a potent, KV7.2/7.3‐specific potassium channel opener in development for the treatment of focal seizures, generalized tonic–clonic seizures, and major depressive disorder; bexicaserin (LP352), a selective 5‐HT2C receptor superagonist in development for the treatment of seizures associated with developmental and epileptic encephalopathies; radiprodil, a selective negative allosteric modulator of NR2B subunit‐containing N‐methyl‐D‐aspartate glutamate receptors, in development for the treatment of seizures and behavior manifestations associated with disorders caused by gain‐of‐function mutations in the GRIN1, −2A, ‐2B, or ‐2D genes; soticlestat (TAK‐935), a selective inhibitor of cholesterol 24‐hydroxylase in development for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome; and STK‐001, an antisense oligonucleotide designed to upregulate Nav1.1 protein expression and improve outcomes in individuals with Dravet syndrome. The diversity in mechanisms of action of these agents illustrates different approaches being pursued in the discovery of novel treatments for seizures and epilepsy. For two of the compounds discussed in this report (azetukalner and soticlestat), clinical evidence of efficacy has already been obtained in a randomized placebo‐controlled adjunctive‐therapy trial. For the other compounds, adequately powered placebo‐controlled efficacy trials have not been completed to date.

2024-06-01·British Journal of Pharmacology

Radiprodil, a selective GluN2B negative allosteric modulator, rescues audiogenic seizures in mice carrying the GluN2A(N615S) mutation

Article

作者: Oberto, Alessandra ; Mirza, Naheed Rohman ; Sprengel, Rolf ; Muglia, Pierandrea ; Eva, Carola Eugenia ; Bertocchi, Ilaria ; Cifarelli, Lorenzo

Background and Purpose:

GRIN‐related disorders are neurodevelopmental disorders caused by mutations in N‐methyl‐D‐aspartate receptor (NMDAR) subunit genes. A large fraction of these mutations lead to a ‘gain of function’ (GoF) of the NMDAR. Patients present with a range of symptoms including epilepsy, intellectual disability, behavioural and motor. Controlling seizures is a significant unmet medical need in most patients with GRIN‐related disorders. Although several hundred GRIN mutations have been identified in humans, until recently none of the mouse models carrying Grin mutations/deletions showed an epileptic phenotype. The two recent exceptions both carry mutations of GluN2A. The aim of this study was to assess the efficacy of radiprodil, a selective negative allosteric modulator of GluN2B‐containing NMDARs, in counteracting audiogenic seizures (AGS) in a murine model carrying the GluN2A(N615S) homozygous mutation (Grin2aS/S mice).

Experimental Approach:

Grin2aS/S mice were acutely treated with radiprodil at different doses before the presentation of a high‐frequency acoustic stimulus commonly used for AGS induction.

Key Results:

Radiprodil significantly and dose‐dependently reduced the onset and severity of AGS in Grin2aS/S mice. Surprisingly, the results revealed a sex‐dependent difference in AGS susceptibility and in the dose‐dependent protection of radiprodil in the two genders. Specifically, radiprodil was more effective in female versus male mice.

Conclusion and Implications:

Overall, our data clearly show that radiprodil, a GluN2B selective negative allosteric modulator, may have the potential to control seizures in patients with GRIN2A GoF mutations. Further studies are warranted to better understand the sex‐dependent effects observed in this study.

2023-01-01·Therapeutic advances in neurological disorders

Pharmacological diversity amongst approved and emerging antiseizure medications for the treatment of developmental and epileptic encephalopathies

Review

作者: Sills, Graeme J.

Developmental and epileptic encephalopathies (DEEs) are rare neurodevelopmental disorders characterised by early-onset and often intractable seizures and developmental delay/regression, and include Dravet syndrome and Lennox–Gastaut syndrome (LGS). Rufinamide, fenfluramine, stiripentol, cannabidiol and ganaxolone are antiseizure medications (ASMs) with diverse mechanisms of action that have been approved for treating specific DEEs. Rufinamide is thought to suppress neuronal hyperexcitability by preventing the functional recycling of voltage-gated sodium channels from the inactivated to resting state. It is licensed for adjunctive treatment of seizures associated with LGS. Fenfluramine increases extracellular serotonin levels and may reduce seizures via activation of specific serotonin receptors and positive modulation of the sigma-1 receptor. Fenfluramine is licensed for adjunctive treatment of seizures associated with Dravet syndrome and LGS. Stiripentol is a positive allosteric modulator of type-A gamma-aminobutyric acid (GABAA) receptors. As a broad-spectrum inhibitor of cytochrome P450 enzymes, its antiseizure effects may additionally arise through pharmacokinetic interactions with co-administered ASMs. Stiripentol is licensed for treating seizures associated with Dravet syndrome in patients taking clobazam and/or valproate. The mechanism(s) of action of cannabidiol remains largely unclear although multiple targets have been proposed, including transient receptor potential vanilloid 1, G protein-coupled receptor 55 and equilibrative nucleoside transporter 1. Cannabidiol is licensed as adjunctive treatment in conjunction with clobazam for seizures associated with Dravet syndrome and LGS, and as adjunctive treatment of seizures associated with tuberous sclerosis complex. Like stiripentol, ganaxolone is a positive allosteric modulator at GABAA receptors. It has recently been licensed in the USA for the treatment of seizures associated with cyclin-dependent kinase-like 5 deficiency disorder. Greater understanding of the causes of DEEs has driven research into the potential use of other novel and repurposed agents. Putative ASMs currently in clinical development for use in DEEs include soticlestat, carisbamate, verapamil, radiprodil, clemizole and lorcaserin.

项与 Radiprodil 相关的新闻（医药）

2024-12-09

·PRNewswire

GRIN Therapeutics Presents Data from Honeycomb Trial of Radiprodil at the American Epilepsy Society Annual Meeting

Previously reported Honeycomb topline results showed radiprodil was generally well-tolerated A key secondary analysis demonstrated a median reduction of 86% in countable motor seizure frequency consistent across GRIN genotypes with gain-of-function variants Company also outlined proposed plans for a Phase 3 pivotal trial expected to begin early 2025 NEW YORK, Dec. 9, 2024 /PRNewswire/ -- GRIN Therapeutics, Inc., a leader in the development of therapies to treat serious neurodevelopmental disorders, presented additional topline data this weekend from the Company's Honeycomb trial, an ongoing global Phase 1b open-label trial evaluating the safety, tolerability, pharmacokinetics and efficacy of radiprodil, an investigational, selective and potent negative allosteric modulator of the N-methyl-D-aspartate receptor subtype 2B (NR2B or GluN2B), in development for the treatment of GRIN-related neurodevelopmental disorder with gain-of-function (GoF) variants. The results, together with an overview of the proposed design of the Company's planned Phase 3 pivotal trial for radiprodil, were presented as a late-breaking poster at the American Epilepsy Society (AES) Annual Meeting in Los Angeles, California. "We are excited to share updated data from the Honeycomb trial, which highlights the significant progress we've made in our effort to bring a new treatment to people living with GRIN-related neurodevelopmental disorder," said Bruce Leuchter, MD, president and chief executive officer of GRIN Therapeutics. "As we plan for the launch of our pivotal Phase 3 trial for radiprodil, we are deeply grateful to the patients and families whose dedication and participation have been instrumental in driving this development program forward. Our team remains fully committed to collaborating closely with regulators, advocates, investigators, clinicians, and the broader community to advance this important research effort as rapidly as possible." As the next phase in the development program for radiprodil, GRIN Therapeutics plans to initiate a randomized, double-blind, placebo-controlled Phase 3 pivotal trial in early 2025, which will include two cohorts of patients with confirmed GoF mutations in the GRIN1, GRIN2A, GRIN2B, or GRIN2D genes, one cohort enrolling patients who have experienced qualifying countable motor seizures (CMS) and a second cohort enrolling patients without qualifying CMS. The proposed Phase 3 pivotal trial was designed based on analysis of positive topline data from the Phase 1b Honeycomb trial in which radiprodil appeared generally well-tolerated, with the most commonly observed adverse events associated with infections or underlying disease symptoms. Patients in the qualifying seizure cohort saw a median reduction of 86% in CMS frequency versus baseline which was consistent across GRIN genotypes. During the trial period, 71% of patients had a greater than 50% reduction in CMS and six of seven were seizure-free during at least 80% of days in the eight-week maintenance period. There were signs of favorable effect on clinical outcomes regardless of the occurrence of seizures as measured by Clinician and Caregiver Global Impressions of Change (CGI-C and CaGI-C) and the Aberrant Behavior Checklist – Community (ABC-C). "GRIN-related neurodevelopmental disorder was first characterized in 2010 and only formally named in 2014. Since then, research and advocacy communities have worked tirelessly to identify approaches to treatment that are both targeted and able to alter the natural course of the disease," said Michael A. Panzara, MD, MPH, chief medical officer of GRIN Therapeutics. "The readout from the Honeycomb trial is an important milestone towards the goal of providing treatment options to patients with and without seizures who suffer from GRIN-related neurodevelopmental disorder with GoF variants. Our plans for a rapid transition to a pivotal Phase 3 study reflect our sense of urgency and commitment to these patients." About GRIN-related neurodevelopmental disorder GRIN-related neurodevelopmental disorder is a family of rare, genetically defined pediatric neurodevelopmental disorders caused by mutations in GRIN genes. While symptoms of GRIN-related neurodevelopmental disorder can present as early as infancy, a diagnosis is often not confirmed until age two or later when a child fails to reach developmental milestones. Individuals may experience developmental delay, intellectual disabilities, epilepsy, muscular hypotonia, movement disorders, spasticity, feeding difficulties and behavioral problems. There are currently no approved therapies for GRIN-related neurodevelopmental disorder. About Radiprodil Radiprodil is an investigational, selective and potent negative allosteric modulator of the N-methyl-D-aspartate (NMDA) receptor subtype 2B (NR2B or GluN2B). In nonclinical studies, radiprodil has been shown to potently and selectively modulate GluN2B. Radiprodil has also demonstrated an antiseizure effect in a number of in vitro and in vivo preclinical seizure and epilepsy models and specifically in models characterized by an enhanced GluN2B NMDA transmission, which can occur with gain-of-function (GoF) mutations in GRIN-related neurodevelopmental disorder. In vitro analysis of brain tissues extracted from both tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) lesions has shown enhanced GluN2B NMDA expression supporting the potential ability of radiprodil to control seizures in these conditions. About GRIN Therapeutics GRIN Therapeutics is dedicated to the research and development of precision therapeutics for pediatric neurodevelopmental disorders with the goal of bringing hope to patients and caregivers. Working to develop novel therapies for patients with neurodevelopmental disorders, the company has two ongoing clinical trials to evaluate radiprodil for the potential treatment of GRIN-related neurodevelopmental disorder and other neurological conditions including tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type II. GRIN Therapeutics is an affiliate of Neurvati Neurosciences, a portfolio company of Blackstone Life Sciences (BXLS). For more information, please visit About Neurvati Neurosciences Neurvati Neurosciences, a portfolio company of Blackstone Life Sciences, identifies and advances the development of high-potential drug candidates across the neuroscience landscape. Neurvati employs a collaborative model that establishes fit-for-purpose affiliate companies, aligning dedicated resources with long-term strategic capital to catalyze innovative treatment options in areas of unmet need. Neurvati's team of experienced operators and drug developers seeks opportunities to challenge current treatment paradigms and make a difference for patients suffering from a wide range of neurological and psychiatric disorders. For more information, please visit About Blackstone Life Sciences Blackstone Life Sciences is an industry-leading private investment platform with capabilities to invest across the life cycle of companies and products within key life science sectors. By combining scale investments and hands-on operational leadership, Blackstone Life Sciences helps bring to market promising new medicines and medical technologies that improve patients' lives and currently has more than $9 billion in assets under management. Corporate Contact Elliott Ruiz +1 201.674.5417 [email protected] ACTIVE/133720412.1 SOURCE GRIN Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床结果临床1期临床3期临床2期

2024-09-15

·药明康德

94%患者肿瘤缩小的靶向疗法；将化疗效果提高40%的抗癌疗法…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. 口服人类表皮生长因子受体2（HER2）酪氨酸激酶抑制剂（TKI）zongertinib治疗非小细胞肺癌（NSCLC）患者在一项早期临床试验中获积极结果，94%患者的肿瘤有缩小。 2. HER2靶向疗法BAY 2927088在一项1/2期临床试验中治疗携带HER2 YVMA插入突变的晚期NSCLC患者，客观缓解率（ORR）达90%。 3. 口服靶向抗癌化合物ibrilatazar联用化疗（紫杉醇/卡铂）在一项1/2期临床试验中使子宫内膜癌患者的无进展生存期（PFS）相比历史对照组延长了40%。药明康德内容团队整理 Zongertinib：公布1b期临床试验的初步数据勃林格殷格翰（Boehringer Ingelheim）公布了旗下口服HER2靶向疗法zongertinib（BI 1810631）在NSCLC患者中的最新积极临床结果。Zongertinib不与野生型表皮生长因子受体（EGFR）结合，进而相关毒性较低。Zongertinib于2023年获得美国FDA授予快速通道资格，并随后于2024年获得美国FDA和中国国家药监局药品审评中心（CDE）授予的突破性疗法认定，用于治疗曾接受过全身性疗法、携带HER2激活突变的晚期NSCLC成人患者。此次公布的结果显示，截至2024年5月，共132例患者每天接受一次120 mg/240 mg zongertinib治疗（n=75/n=57）。经盲法独立中央审评（BICR）评估，试验达到主要终点，患者的确认ORR为66.7%（97.5% CI：53.8–77.5，p<0.0001）。在所有剂量的患者中，94%的患者观察到任何程度的肿瘤缩小。此外，数据还显示，zongertinib具有初步的脑活性。根据BICR评估的RANO-BM（神经肿瘤脑转移瘤的疗效评估），33%（120 mg，n=27）和40%（240 mg，n=25）的无症状脑转移患者达成确认的客观缓解，疾病控制率（DCR）分别为74%和92%。Zongertinib在120 mg和240 mg剂量下的耐受性通常良好，没有因治疗导致的死亡，且导致剂量减少（11%）和停药（3%）的不良事件发生率低。 BAY 2927088：公布1/2期临床试验数据拜耳（Bayer）公布了1/2期SOHO-01研究扩展部分的积极结果。该研究评估了其口服、可逆的HER2靶向疗法BAY 2927088在携带HER2变异的晚期NSCLC患者中的安全性和初步疗效。入组患者在接受≥1种晚期疾病全身治疗后病情出现进展，但未曾接受过HER2靶向治疗。BAY 2927088能够强效抑制突变的HER2，包括HER2外显子20插入突变和HER2点突变，同时也能抑制EGFR，对突变型EGFR具有高选择性，且不和野生型EGFR相结合。美国FDA和中国药品审评中心于2024年授予BAY 2927088突破性疗法认定，用于治疗携带HER2激活突变且曾接受过全身治疗的不可切除或转移性NSCLC成年患者。此次公布的结果显示，43名可评估疗效患者的确认ORR为72.1%，1名（2.3%）患者实现完全缓解（CR）。中位缓解持续时间（DOR）和PFS分别为8.7个月和7.5个月。在携带HER2 YVMA插入突变（最常见的变异）的患者中，ORR为90.0%，DOR为9.7个月，PFS为9.9个月。此外，BAY 2927088的安全性是可控的，并且与之前的报告一致。 Ibrilatazar（ABTL0812）：公布1/2期临床试验数据 AbilityPharma公司公布了ibrilatazar联用化疗（紫杉醇/卡铂）治疗晚期或复发性子宫内膜癌患者的1/2期临床试验ENDOLUNG的最终数据。Ibrilatazar是一种潜在“first-in-class”、差异化的口服靶向抗癌化合物，通过诱导内质网应激和抑制PI3K/Akt/mTOR通路来引发自噬。在临床试验中，ibrilatazar对子宫内膜癌和肺癌患者显示出临床益处。此外，它在包括肺癌、子宫内膜癌、胰腺癌、神经母细胞瘤和胶质母细胞瘤等癌症类型的动物模型中展示了强有力的临床前概念验证。此次公布的结果显示，ibrilatazar联用化疗的总缓解率为65.8%，其中13.2%的患者达到CR，52.6%的患者达到部分缓解（PR），中位DOR为7.4个月。中位PFS为9.8个月，相比历史对照组延长了40%。中位总生存期（OS）为23.6个月。这些结果表明，接受ibrilatazar联用化疗治疗的患者的ORR、PFS和OS相较于历史对照组（分别为51%、7.1个月和20.4个月）均有所提高。安全性方面，ibrilatazar联用化疗治疗显示出良好的安全性，未引入与化疗相关的重大不良事件，其安全性与历史对照组一致。药代动力学参数与临床前试验中观察到的靶点作用相符，血液药效学生物标志物表明治疗开始后至少28天内靶点调节持续存在。 RLY-2608：公布首个人体试验数据 Relay Therapeutics公司公布了其在研疗法RLY-2608的首个人体试验的积极中期数据。RLY-2608是Relay Therapeutics开发针对PI3Kα突变体的选择性抑制剂。该激酶是所有癌症中最常出现突变的激酶之一，约在14%的实体瘤患者检测出PI3Kα的致癌突变。传统上，PI3Kα抑制剂的开发聚焦于蛋白的活性位点。然而，这些抑制剂缺乏对突变型PI3Kα的选择性，导致治疗效果欠佳。为了增强PI3Kα抑制剂的选择性，Relay Therapeutics解析了PI3Kα的全长蛋白冷冻电镜结构，以阐明野生型和突变型PI3Kα的构象差异，并利用这些见解支持RLY-2608的设计。此次公布的数据显示，此前接受过大量治疗，携带PI3Kα突变的HR阳性、HER2阴性局部晚期或转移性乳腺癌患者在接受RLY-2608（600 mg）联合fulvestrant治疗后，表现出具有临床意义的PFS。中位随访时间为7.5个月时，所有携带PI3Kα突变患者的中位PFS为9.2个月。在30名具有可测量疾病的患者中，1/3的患者达到PR，ORR为33%。新闻稿指出，RLY-2608是首个针对PI3Kα，具有突变体和异构体（isoform）选择性的别构抑制剂。 ▲RLY-2608让73%患者的肿瘤缩小（图片来源：Relay Therapeutics公司官网） Mosliciguat：公布1b期临床试验数据 Roivant公司公布了其肺动脉高压（PH）疗法mosliciguat的1b期概念验证试验的结果。Mosliciguat是一种每日给药一次、潜在"first-in-class"和“best-in-class”的吸入性可溶性鸟苷酸环化酶（sGC）激动剂，可靶向递送至肺部。sGC是一种一氧化氮（NO）/环磷酸鸟苷（cGMP）信号通路中的关键酶，可催化cGMP生成，从而增加血管扩张、减少炎症和细胞凋亡、逆转血管重塑和抗纤维化作用。与需要减少血红素和NO才能对sGC产生作用的sGC激动剂不同，mosliciguat是一种独立于血红素和NO的sGC激活剂。这使mosliciguat可能在典型PH患者体内高氧化环境中保持有效性。该疗法目前正在开发用于治疗与间质性肺病（PH-ILD）相关的肺动脉高压。此次公布的结果显示，1.0、2.0和4.0毫克mosliciguat分别使患者的肺血管阻力（PVR）相对于基线的平均最大峰值降低达25.9%、38.1%和36.3%，超过预定主要结果≥20%降幅的阈值。此外，该疗法的耐受性良好，治疗引起的不良事件发生率低。根据新闻稿，这是迄今为止PH相关试验中观察到PVR的最大降低幅度之一。Mosliciguat的全球2期PHocus研究即将启动。 CT-996：公布1期临床试验数据罗氏（Roche）公布了其每日一次的口服胰高血糖素样肽-1（GLP-1）受体小分子激动剂CT-996的1期临床试验结果。罗氏在去年12月与Carmot Therapeutics达成合并协议，斥资约31亿美元收购了Carmot公司，囊获包括CT-996在内的多款处于临床开发阶段的皮下和口服肠促胰岛素疗法。此次公布的结果显示，CT-996在未患有2型糖尿病的肥胖人群中，在4周内将受试者体重减轻7.3%（约7公斤），安慰剂同期将体重降低1.2%。与安慰剂相比，CT-996提供了具有临床意义的体重减轻。安全性方面，所有的治疗伴发不良事件（TEAE）均为轻度或中度，没有发现3级以上TEAE。没有出现与在研药物相关的停止用药。最常见的TEAE为胃肠道相关不良事件，与其它肠促胰岛素疗法类似。接受更高剂量治疗的参与者TEAE更多，不过更缓慢的剂量滴定可能改善耐受性。基于这些积极结果，该公司计划在2025年启动2期临床试验。 ▲CT-996的减重效果（图片来源：参考资料[5]） Radiprodil：公布1b期临床试验数据 GRIN Therapeutics公司公布了其正在进行的全球1b期开放标签临床试验的初步结果。该试验的两个部分正在评估radiprodil的安全性、耐受性、药代动力学以及疗效。Radiprodil是一种在研选择性强效N-甲基-D-天冬氨酸受体亚基2B（GluN2B）的负变构调节剂，用于治疗GRIN相关神经发育障碍。GRIN相关神经发育障碍是一组由GRIN基因突变引起的罕见儿科神经发育障碍，目前尚无批准的疗法。此次公布的结果显示，radiprodil在具有GRIN基因功能增加突变的患者中，无论基线时是否存在可数的运动性癫痫发作（CMS），均表现出良好的耐受性。具有CMS患者的中位癫痫发作频率与基线相比降低了86%，超过了背景抗癫痫药物，其中71%的患者癫痫发作频率降低了50%以上。这些结果预计将支持GRIN Therapeutics与监管机构的讨论，以推动radiprodil进入3期关键性试验。 Elraglusib：公布1/2期临床试验的新数据 Actuate Therapeutics公司更新了elraglusib用于治疗复发/难治性尤文氏肉瘤（r/r EWS）的1/2期临床试验进展。该研究旨在评估elraglusib在复发/难治性恶性肿瘤儿科患者中的安全性和疗效，涵盖EWS及EWS相关的小圆细胞肉瘤。所有患者均接受了elraglusib与环磷酰胺/拓扑替康的联合治疗。此次公布的结果显示，在首批8名复发/难治性EWS及相关肉瘤患者中，两名患者正在经历持续的CR，两名患者实现疾病稳定（SD），1名患者取得了PR，肿瘤缩小了52%。Elraglusib展现了抗肿瘤活性，DCR为62.5%。该研究招募正在进行，预计2025年上半年有望公布顶线数据。 ▲Elraglusib联用环磷酰胺/拓扑替康的1/2期临床试验结果（图片来源：参考资料[6]） ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] Relay Therapeutics Announces Positive Interim Data for RLY-2608 Demonstrating Clinically Meaningful Progression Free Survival. Retrieved September 9, 2024, from https://ir.relaytx.com/news-releases/news-release-details/relay-therapeutics-announces-positive-interim-data-rly-2608 [2] Boehringer’s zongertinib shows encouraging efficacy and tolerability profile in previously treated HER2 mutated lung cancer patients. Retrieved September 10, 2024 from https://www.boehringer-ingelheim.com/human-health/cancer/lung-cancer/zongertinib-positive-results-non-small-cell-lung-cancer [3] New results from the Investigational agent BAY 2927088 in HER2-mutant non-small cell lung cancer (NSCLC) presented at WCLC. Retrieved September 10, 2024 from https://www.businesswire.com/news/home/20240909979023/en/New-results-from-the-Investigational-agent-BAY-2927088-in-HER2-mutant-non-small-cell-lung-cancer-NSCLC-presented-at-WCLC [4] Roivant Unveils New Pipeline Program Mosliciguat, A Potential First-In-Class and Best-In-Category Inhaled Once-Daily Soluble Guanylate Cyclase (sGC) Activator. Retrieved September 10, 2024 from https://www.globenewswire.com/news-release/2024/09/10/2943472/0/en/Roivant-Unveils-New-Pipeline-Program-Mosliciguat-A-Potential-First-In-Class-and-Best-In-Category-Inhaled-Once-Daily-Soluble-Guanylate-Cyclase-sGC-Activator.html [5] Safety, Pharmacokinetics, and Pharmacodynamics of CT-996, an Oral Small-Molecule, Signal-Biased GLP-1 Receptor Agonist Over 4 Weeks in Adults With Obesity. Retrieved September 11, 2024, from https://medically.roche.com/global/en/metabolism/easd-2024/medical-material/EASD-2024-presentation-chakravarthy-ct-996-an-oral-small-molecule-signal-biased-pdf.html [6] Actuate Therapeutics Obtains Complete Responses and Provides Update on Clinical Trial of Elraglusib for the Treatment of Relapsed/Refractory Ewing Sarcoma. Retrieved September 14, 2024, from https://actuatetherapeutics.com/press_releases/actuate-therapeutics-obtains-complete-responses-and-provides-update-on-clinical-trial-of-elraglusib-for-the-treatment-of-relapsed-refractory-ewing-sarcoma/ [7] IBRILATAZAR (ABTL0812) from AbilityPharma increases chemotherapy effectiveness by 40% in patients with endometrial cancer. Retrieved September 14, 2024, from https://abilitypharma.com/en/main-menu/media-center-2/press-release/ibrilatazar-(abtl0812)-from-abilitypharma-increases-chemotherapy-effectiveness-by-40-in-patients-with-endometrial-cancer [8] GRIN Therapeutics Announces Positive Topline Data from Honeycomb Trial of Radiprodil in GRIN-Related Neurodevelopmental Disorder. Retrieved September 14, 2024, from https://www.prnewswire.com/news-releases/grin-therapeutics-announces-positive-topline-data-from-honeycomb-trial-of-radiprodil-in-grin-related-neurodevelopmental-disorder-302240847.html [9] Seres Therapeutics Reports SER-155 Phase 1b Placebo-Controlled Cohort 2 Study Safety and Clinical Results in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (allo-HSCT). Retrieved September 13, 2024, from https://www.globenewswire.com/news-release/2024/09/12/2945049/0/en/Seres-Therapeutics-Reports-SER-155-Phase-1b-Placebo-Controlled-Cohort-2-Study-Safety-and-Clinical-Results-in-Patients-Undergoing-Allogeneic-Hematopoietic-Stem-Cell-Transplant-allo-.html [10] Vironexis Biotherapeutics Launches with FDA Clearance of IND Application for First-Ever Clinical Trial of an AAV-delivered Cancer Immunotherapy. Retrieved September 13, 2024, from https://www.globenewswire.com/news-release/2024/09/12/2945063/0/en/Vironexis-Biotherapeutics-Launches-with-FDA-Clearance-of-IND-Application-for-First-Ever-Clinical-Trial-of-an-AAV-delivered-Cancer-Immunotherapy.html [11] Cytonics Announces Completion Of Enrollment For Phase 1 Clinical Study Evaluating CYT-108, A Novel Recombinant Protease Inhibitor, In Patients Suffering From Osteoarthritis Of The Knee. Retrieved September 13, 2024, from https://www.prnewswire.com/news-releases/cytonics-announces-completion-of-enrollment-for-phase-1-clinical-study-evaluating-cyt-108-a-novel-recombinant-protease-inhibitor-in-patients-suffering-from-osteoarthritis-of-the-knee-302239925.html [12] Phanes Therapeutics Announces First Patient Dosed in Clinical Study of PT886 in Combination with Chemotherapy. Retrieved September 13, 2024, from https://www.prnewswire.com/news-releases/phanes-therapeutics-announces-first-patient-dosed-in-clinical-study-of-pt886-in-combination-with-chemotherapy-302242421.html [13] Upstream Bio Announces Oral Presentation of New Data from a Phase 1b Multiple Ascending Dose Trial of Verekitug (UPB-101) in Adults with Asthma at the European Respiratory Society Congress. Retrieved September 13, 2024, from https://www.globenewswire.com/news-release/2024/09/09/2942765/0/en/Upstream-Bio-Announces-Oral-Presentation-of-New-Data-from-a-Phase-1b-Multiple-Ascending-Dose-Trial-of-Verekitug-UPB-101-in-Adults-with-Asthma-at-the-European-Respiratory-Society-Co.html [14] CytomX Therapeutics Announces First Patient Dosed with CX-801, a Dually-Masked Interferon-Alpha 2b PROBODY®, in a Phase 1 Study in Patients with Solid Tumors. Retrieved September 13, 2024, from https://www.globenewswire.com/news-release/2024/09/09/2942754/37704/en/CytomX-Therapeutics-Announces-First-Patient-Dosed-with-CX-801-a-Dually-Masked-Interferon-Alpha-2b-PROBODY-in-a-Phase-1-Study-in-Patients-with-Solid-Tumors.html#:~:text=SOUTH%20SAN%20FRANCISCO%2C%20Calif.%2C%20Sept.%2009%2C%202024%20%28GLOBE,1%20study%20%28NCT06462794%29%20in%20patients%20with%20solid%20tumors. [15] ORYZON announces first patient dosed in an Investigator-initiated Phase Ib study of iadademstat in first-line acute myeloid leukemia. Retrieved September 13, 2024, from https://www.oryzon.com/en/news-events/news/oryzon-announces-first-patient-dosed-investigator-initiated-phase-ib-study [16] PolTREG Treg cell therapy for patients with type-1 diabetes shows long-term clinical remission and insulin independence. Retrieved September 13, 2024, from https://poltreg.com/poltreg-treg-cell-therapy-for-patients-with-type-1-diabetes-shows-long-term-clinical-remission-and-insulin-independence/ [17] Centessa Announces Positive Interim Phase 1 Clinical Data with its Novel Orexin Receptor 2 (OX2R) Agonist, ORX750, in Acutely Sleep-Deprived Healthy Volunteers. Retrieved September 13, 2024, from https://investors.centessa.com/news-releases/news-release-details/centessa-announces-positive-interim-phase-1-clinical-data-its [18] Cytokinetics Announces Data From Phase 1 Study of CK-4021586. Retrieved September 13, 2024, from https://www.globenewswire.com/news-release/2024/09/09/2942724/35409/en/Cytokinetics-Announces-Data-From-Phase-1-Study-of-CK-4021586.html [19] Antennova to Present Latest Data of ATN-037 in a Mini Oral Presentation at ESMO Congress. Retrieved September 13, 2024, from https://www.prnewswire.com/news-releases/antennova-to-present-latest-data-of-atn-037-in-a-mini-oral-presentation-at-esmo-congress-2024-302240448.html [20] TILT Biotherapeutics Presents Clinical Data on TILT-123 After Fully Intravenous Delivery Regimen at ESMO 2024. Retrieved September 13, 2024, from https://www.globenewswire.com/news-release/2024/09/09/2942525/0/en/TILT-Biotherapeutics-Presents-Clinical-Data-on-TILT-123-After-Fully-Intravenous-Delivery-Regimen-at-ESMO-2024.html [21] Terns Pharmaceuticals Announces Positive Phase 1 Clinical Trial Results with TERN-601 Once-Daily Oral GLP-1R Agonist for the Treatment of Obesity. Retrieved September 9, 2024 from https://ir.ternspharma.com/news-releases/news-release-details/terns-pharmaceuticals-announces-positive-phase-1-clinical-trial [22] Zealand Pharma announces positive topline results from 13-week Phase 1b multiple ascending dose clinical trial with GLP-1/GLP-2 receptor dual agonist dapiglutide. Retrieved September 9, 2024 from https://www.globenewswire.com/news-release/2024/09/09/2943004/0/en/Zealand-Pharma-announces-positive-topline-results-from-13-week-Phase-1b-multiple-ascending-dose-clinical-trial-with-GLP-1-GLP-2-receptor-dual-agonist-dapiglutide.html [23] BridgeBio Receives FDA’s Regenerative Medicine Advanced Therapy (RMAT) Designation for BBP-812 Canavan Disease Gene Therapy Program. Retrieved September 11, 2024 from https://www.globenewswire.com/news-release/2024/09/10/2944157/0/en/BridgeBio-Receives-FDA-s-Regenerative-Medicine-Advanced-Therapy-RMAT-Designation-for-BBP-812-Canavan-Disease-Gene-Therapy-Program.html [24] NKGen Biotech’s Positive Phase 1 Clinical Data in Moderate Alzheimer’s Disease Advances Troculeucel into Phase 2 with First Patient Dosed in Phase 1/2a Trial. Retrieved September 12, 2024, from https://www.globenewswire.com/news-release/2024/09/12/2945163/0/en/NKGen-Biotech-s-Positive-Phase-1-Clinical-Data-in-Moderate-Alzheimer-s-Disease-Advances-Troculeucel-into-Phase-2-with-First-Patient-Dosed-in-Phase-1-2a-Trial.html [25] HotSpot Therapeutics Presents First-in-Human Phase 1 Clinical Data on its Novel CBL-B Inhibitor, HST-1011, at ESMO Congress 2024. Retrieved September 13, 2024, from https://www.prnewswire.com/news-releases/hotspot-therapeutics-presents-first-in-human-phase-1-clinical-data-on-its-novel-cbl-b-inhibitor-hst-1011-at-esmo-congress-2024-302246957.html [26] Sernova Announces New Positive Data from Phase I/II Trial Regarding Islet Survival and Function. Retrieved September 13, 2024, from https://www.globenewswire.com/news-release/2024/09/12/2945121/0/en/Sernova-Announces-New-Positive-Data-from-Phase-I-II-Trial-Regarding-Islet-Survival-and-Function.html [27] VYNE Therapeutics Announces Positive Phase 1a SAD Data for VYN202, a Novel BD2-Selective BET Inhibitor. Retrieved September 13, 2024, from https://www.globenewswire.com/news-release/2024/09/12/2945109/0/en/VYNE-Therapeutics-Announces-Positive-Phase-1a-SAD-Data-for-VYN202-a-Novel-BD2-Selective-BET-Inhibitor.html 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，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。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

突破性疗法临床结果快速通道临床2期

2024-09-09

·PRNewswire

GRIN Therapeutics Announces Positive Topline Data from Honeycomb Trial of Radiprodil in GRIN-Related Neurodevelopmental Disorder

- Radiprodil appeared to be generally well-tolerated in patients with gain-of-function (GoF) variants in GRIN genes, both with and without countable motor seizures (CMS) at baseline - Patients with CMS saw a median reduction of 86% in seizure frequency from baseline, over and above background anti-seizure medications, with 71% experiencing a greater than 50% reduction - Results are expected to support planned discussions with regulators to potentially advance radiprodil to a Phase 3 pivotal trial - GRIN Therapeutics is backed by a $200 million capital commitment from Blackstone Life Sciences NEW YORK, Sept. 9, 2024 /PRNewswire/ -- GRIN Therapeutics, Inc., a leader in the development of therapies to treat serious neurodevelopmental disorders, reported topline results from the Company's ongoing two-part global Phase 1b open-label trial evaluating the safety, tolerability, pharmacokinetics, and efficacy of radiprodil, an investigational, selective and potent negative allosteric modulator of the N-methyl-D-aspartate receptor subtype 2B (NR2B or GluN2B), in the treatment of GRIN-related neurodevelopmental disorder. The results were presented in a podium presentation yesterday at the International League Against Epilepsy (ILAE) 15th European Epilepsy Conference in Rome, Italy. "The results of this trial are very encouraging as they suggest that radiprodil has the potential to substantially reduce the occurrence of seizures and possibly improve behaviors in children with gain-of-function mutations who are not responding well to current treatments," said Prof. Renzo Guerrini, MD, FRCP, FAES, Director, Neuroscience and Human Genetics Department, Phase 1 Clinical Trial Centre, Children's Hospital A. Meyer IRCCS, University of Florence, Italy. "Given these initial efficacy data and promising safety profile, we look forward to continuing to advance this important research program into the next phase of development." The Honeycomb study enrolled 15 pediatric patients with confirmed GoF mutations in the GRIN1, GRIN2A, or GRIN2B genes. The primary objectives of the study were to assess the safety and pharmacokinetics of radiprodil, while key secondary objectives focused on evaluating efficacy on both seizures and non-seizure outcomes. At study enrollment, patients were divided into two cohorts based on the frequency of countable motor seizures (CMS) they experienced during a 28-day screening period (Cohort 1) and baseline severity of non-seizure behavioral symptoms (Cohort 2). Following screening and observation periods, patients were escalated from a starting dose level of 0.05 mg/kg based on tolerability, pharmacokinetics, and predicted GluN2B receptor occupancy to a dose level to be maintained through an eight-week maintenance period. Part B of the Honeycomb study, an open-label extended treatment period for patients who completed Part A and were eligible for continued study treatment, remains ongoing. As of the July 15 data cut, 15 patients were available for analysis. Demographics and baseline disease characteristics were representative of the targeted GRIN population and generally balanced between the seizure (Cohort 1) and non-seizure behavior (Cohort 2) cohorts. There was a high level of seizure activity at baseline in Cohort 1 with a mean of 37.0 and a median of 25.5 CMS per patient (range of 4.8 to 85.9). There were zero CMS at baseline in Cohort 2. Radiprodil appeared generally well tolerated throughout Part A and B of the study to date. The treatment-emergent adverse events (TEAEs) most commonly observed (i.e., in three or more patients) were those associated with infections or underlying disease symptoms including pyrexia, diarrhea, respiratory tract infection, abnormal behavior, agitation, cough, dystonia, fatigue, and gastroenteritis. There were no deaths in the study. Three patients experienced a serious adverse event (one patient each with obstructive bronchitis, viral pneumonia, or adenovirus infection). None were considered related to treatment with radiprodil and none met study stopping rule criteria. During Part A of the study, patients treated with radiprodil showed a median reduction of 86% in seizure frequency versus baseline, which was a key secondary endpoint in the trial. During this same period, 71% of patients had a greater than 50% reduction in CMS, with 43% seeing a greater than 90% reduction and one patient being seizure free. Clinicians and caregivers also generally assessed patients as improved clinically over the course of the study. "We believe the findings from the Honeycomb study in gain-of-function patients with treatment resistant symptoms provide strong rationale to progress this promising program into Phase 3 development as quickly as possible," said Bruce Leuchter, MD, President and Chief Executive Officer at Neurvati Neurosciences and GRIN Therapeutics. "I am proud of the progress we have made to address the profound unmet need in GRIN-related neurodevelopmental disorder since we launched the company three years ago with an investment from Blackstone Life Sciences. These compelling data represent the first major milestone in our development plans for radiprodil and will help us build new levels of momentum toward achieving our goal of bringing the first approved treatment to patients living with GRIN-related neurodevelopmental disorder." About GRIN-related neurodevelopmental disorder: GRIN-related neurodevelopmental disorder is a family of rare, genetically defined pediatric neurodevelopmental disorders caused by mutations in GRIN genes. While symptoms of GRIN-related neurodevelopmental disorder can present as early as infancy, a diagnosis is often not confirmed until age two or later when a child fails to reach developmental milestones. Individuals may experience developmental delay, intellectual disabilities, epilepsy, muscular hypotonia, movement disorders, spasticity, feeding difficulties and behavioral problems. There are currently no approved therapies for GRIN-related neurodevelopmental disorder. About Radiprodil: Radiprodil is an investigational, selective and potent negative allosteric modulator of the N-methyl-D-aspartate receptor subtype 2B (NR2B or GluN2B). In nonclinical studies, radiprodil has been shown to potently and selectively modulate the N-methyl-D-aspartate (NMDA) receptor subtype 2B (NR2B or GluN2B). Radiprodil has also demonstrated an antiseizure effect in a number of in vitro and in vivo preclinical seizure and epilepsy models and specifically in models characterized by an enhanced GluN2B-NMDA transmission, which can occur with gain-of-function (GoF) mutations in GRIN-related disorder. About GRIN Therapeutics: GRIN Therapeutics is dedicated to the research and development of precision therapeutics for pediatric neurodevelopmental disorders with the goal of bringing hope to patients and caregivers. Working to develop the investigational product radiprodil as a novel therapy for patients with neurodevelopmental disorders, the company has two ongoing clinical trials to evaluate radiprodil for the potential treatment of GRIN-related neurodevelopmental disorder and other neurological conditions including tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type II. GRIN Therapeutics is an affiliate of Neurvati Neurosciences, a portfolio company of Blackstone Life Sciences (BXLS). For more information, please visit About Neurvati Neurosciences Neurvati Neurosciences, a portfolio company of Blackstone Life Sciences, identifies and advances the development of high-potential drug candidates across the neuroscience landscape. Neurvati employs a collaborative model that establishes fit-for-purpose affiliate companies, aligning dedicated resources with long-term strategic capital to catalyze innovative treatment options in areas of unmet need. Neurvati's team of experienced operators and drug developers seeks opportunities to challenge current treatment paradigms and make a difference for patients suffering from a wide range of neurological and psychiatric disorders. For more information, please visit . About Blackstone Life Sciences Blackstone Life Sciences is an industry-leading private investment platform with capabilities to invest across the life cycle of companies and products within key life science sectors. By combining scale investments and hands-on operational leadership, Blackstone Life Sciences helps bring to market promising new medicines and medical technologies that improve patients' lives and currently has more than $9 billion in assets under management. Corporate Contact: Elliott Ruiz +1 201.674.5417 [email protected] SOURCE GRIN Therapeutics Inc.

临床结果临床1期临床3期

100 项与 Radiprodil 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12260

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
婴儿痉挛	临床2期	法国	UCB Biopharma SRL	2017-12-04
糖尿病周围神经性疼痛	临床2期	美国	Gedeon Richter (UK) Ltd.	2009-02-01
糖尿病周围神经性疼痛	临床2期	美国	Forest Laboratories, Inc.	2009-02-01
糖尿病性神经病变	临床2期	-	UCB SA	-
肌肉痉挛	临床2期	-	UCB SA	-
肌肉痉挛	临床2期	-	Chemical Works of Gedeon Richter Plc	-
肌肉痉挛	临床2期	-	Forest Laboratories, Inc.	-
特发性肺纤维化	临床前	加拿大	Algernon Pharmaceuticals, Inc.	2019-06-09
帕金森病	临床前	美国	UCB SA	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02647697 (Pubmed \| Pharmacol Res Perspect)	临床1期	-	10	Radiprodil oral suspension	鹽鏇淵糧選齋憲夢簾廠(繭醖膚窪衊獵襯糧壓蓋) = 膚鑰顧網醖繭選膚膚廠積窪鏇觸範醖淵蓋壓鏇 (觸襯餘製鹹網遞廠鹽廠 ) 更多	-	2019-02-01
SFN2013	N/A	-	-	radiprodil (Aß1-42)	夢築蓋遞淵遞鬱夢願膚(獵蓋衊構醖製築觸鑰製) = 範膚襯鹽壓顧廠廠糧窪蓋醖淵糧衊繭願顧壓觸 (獵顧簾壓積餘簾願構鹹 )	-	2013-11-12
SFN2013	N/A	-	-	radiprodil (Aß1-40)	夢築蓋遞淵遞鬱夢願膚(獵蓋衊構醖製築觸鑰製) = 醖廠憲醖廠壓簾鑰膚窪蓋醖淵糧衊繭願顧壓觸 (獵顧簾壓積餘簾願構鹹 )	-	2013-11-12