A Phase 1/2, Open-Label, Dose-Escalation, Dose-Expansion Study of DSP-5336 in Adult Patients with Acute Leukemia and Other Selected Hematologic Malignancies, with and Without Mixed Lineage Leukemia (MLL) Rearrangement or Nucleophosmin 1 (NPM1) Mutation

A Phase 1/2 dose escalation / dose expansion study of DSP 5336 in patients with relapsed or refractory AML.

开始日期2022-02-28

申办/合作机构

Sumitomo Pharma America, Inc.

100 项与 Enzomenib 相关的临床结果

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100 项与 Enzomenib 相关的转化医学

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100 项与 Enzomenib 相关的专利（医药）

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项与 Enzomenib 相关的文献（医药）

2023-09-01·Journal of cancer research and clinical oncology

Targeting the undruggable: menin inhibitors ante portas.

Review

作者: Desole, Maximilian ; Sica, Simona ; Dempke, Wolfram C M ; Schmidt-Hieber, Martin ; Chiusolo, Patrizia

Acute myeloid leukaemias harbouring a rearrangement of the mixed lineage leukaemia gene (MLL) are aggressive haematopoietic malignancies that relapse early and have a poor prognosis (event-free survival less than 50%). Menin is a tumour suppressor, however, in MLL-rearranged leukaemias it functions as a co-factor which is mandatory for the leukaemic transformation by interaction with the N-terminal part of MLL, which is maintained in all MLL-fusion proteins. Inhibition of menin blocks leukaemogenesis and leads to differentiation and, in turn, to apoptosis of leukaemic blasts. Furthermore, nucleophosmin 1 (NPM1) binds to specific chromatin targets, which are co-occupied by MLL, and menin inhibition has been shown to trigger degradation of mNPM1 resulting in a rapid decrease in gene expression and activating histone modifications. Therefore, disruption of the menin-MLL axis blocks leukaemias driven by NPM1 mutations for which the expression of menin-MLL target genes (e.g., MEIS1, HOX etc.) is essential. To date at least six different menin-MLL inhibitors are undergoing clinical evaluation as first- and second-line monotherapy in acute leukaemias: DS-1594, BMF-219, JNJ-75276617, DSP-5336, revumenib, and ziftomenib, however, only for revumenib and ziftomenib early clinical data have been reported. In the revumenib phase I/II AUGMENT-101 trial (N = 68) with very heavily pretreated AML patients the ORR was 53% with a CR rate of 20%. The ORR in patients harbouring MLL rearrangement of mNPM1 was 59%. Patients who achieved a response had a mOS of 7 months. Similar results have been reported for ziftomenib in the phase I/II COMET-001 trial. ORR was 40% and CRc was 35% in AML patients with mNPM1. However, outcome was worse in AML patients with a MLL rearrangement (ORR 16.7%, CRc 11%). Differentiation syndrome was a notable adverse event. The clinical development of novel menin-MLL inhibitors is well in line with the currently ongoing paradigm shift towards targeted therapies seen in the AML treatment landscape. Moreover, the clinical assessment of combinations of these inhibitors with established therapy options in AML could be the fuel for an improved outcome of MLL/NPM1 patients.

项与 Enzomenib 相关的新闻（医药）

2024-07-27

·药渡Daily

【药渡药闻报告-创新药篇】-2024年第28期/总第149期

全球药物批准/研发动态 01 全球新药批准情况根据药渡数据统计分析，本次统计周期（2024.07.13-07.19）全球（不含中国）共有2个新药获批上市。其中，BLA批准1个，新适应症批准1个。本次批准新药数量与上个统计周期相同。 7月15日，Daewoong Pharmaceutical宣布其肉毒杆菌毒素产品Nabota获得了阿根廷ANMAT的批准，剂量为100个单位和200个单位，商品名为Clodew。Daewoong计划于今年第四季度通过其合作伙伴Oxapharma S.A.在阿根廷推出Crodew。这是第一个也是唯一一个在阿根廷获得批准的韩国肉毒杆菌毒素，利用Clodew的批准，未来可扩大Daewoong在拉丁美洲BTX市场的影响力。 7月18日，Phathom Pharmaceuticals宣布，FDA已批准VOQUEZNA（Vonoprazan）10毫克片剂，用于缓解与成人非糜烂性胃食管反流病相关的胃灼热。该药物也被批准用于治疗所有严重程度的糜烂性食管炎（EE），并与抗生素联合用于根除幽门螺杆菌（H. pylori）感染。研究结果显示，服用VOQUEZNA的患者无胃灼热天数的平均百分比为45%，安慰剂组为28%（p<0.001），24小时无胃灼热天数的中位数百分比分别为48%和17%。全球（不含中国）新药批准情况（部分） 02 全球新药申报进展根据药渡数据统计分析，本次统计周期（2024.07.13-07.19）全球（不含中国）共有6个新药申报上市。其中，NDA申报1个，BLA申报5个。与上次统计周期相比，本次增加4个NDA/BLA申报。 7月19日，百奥泰宣布BAT2206乌司奴单抗注射液的生物制品上市申请获FDA和EMA受理。BAT2206是IL-12和IL-23共有的p40亚基的全人源单克隆抗体，IL-12和IL-23可与p40亚基结合，破坏IL-12和IL-23介导的信号传导和细胞因子的效应。 NDA/BLA申报（部分）根据药渡数据统计分析，本次统计周期（2024.07.13-07.19）全球（不含中国）共有5个药物获监管机构特殊资格认定。其中，化学药2个，生物药1个，细胞疗法2个。与上次统计周期相比，本次增加1个获监管机构特殊资格认定的药物。 7月15日，SMPA宣布FDA授予DSP-5336快速通道资格，用于治疗患有KMT2A重排[也称为混合谱系白血病重排（MLLr）或核磷蛋白突变（NPM1m）]的复发或难治性急性髓系白血病（AML）患者。DSP-5336是一种研究性小分子menin和混合谱系白血病（MLL）蛋白相互作用抑制剂，I/II期研究临床结果显示57%的患者观察到客观反应，其中包括具有核磷蛋白1（NPM1）突变和KMT2A（MLL）重排的患者的反应，完全缓解或完全缓解伴部分血液学恢复（CR/CRh）的比例为24%。 7月16日，迈威生物宣布FDA授予7MW3711（B7-H3 ADC）孤儿药资格认定，用于治疗小细胞肺癌。7MW3711注射人体后，可与肿瘤细胞表面的抗原B7-H3结合内吞进入肿瘤细胞，通过特定酶解作用，定向释放小分子，从而实现对肿瘤的精准杀伤。7MW3711具有结构稳定，组分均一，纯度高，易于产业化放大等特点，同时具有良好的药物安全性及药代特性。特殊资格认定情况 03 全球新药研发进展根据药渡数据统计分析，本次统计周期（2024.07.13-07.19）全球（不含中国）新药临床研发状态更新共计34条，涉及肿瘤、血液和淋巴疾病、遗传代谢病、神经疾病以及皮肤病等共计13个领域。其中，眼部疾病领域临床进展更新居各领域之首，为5条：涉及化学药1条，生物药4条。 7月16日，邦耀生物宣布，其与华东师范大学、上海长征医院合作的CAR-T疗法（TyU19）治疗自身免疫疾病研究成果于7月15日正式在Cell上发表，也是顶级期刊Cell首次发表CAR-T治疗自免疾病的研究成果。研究团队使用TyU19治疗了3例难治性自身免疫性疾病患者：1例为免疫介导的坏死性肌炎（IMNM）、2例为系统性硬化症（SSc）。IMNM受试者接受治疗后，未出现任何发热以及细胞因子风暴的症状，且总改善评分迅速从基线的72.5上升至100。2名患有严重SSc的受试者在接受治疗后，CRISS评分显著提高，修改后的Rodnan皮肤评分（mRSS）显著下降。此外，在经TyU19治疗后所有患者的B细胞均被完全清除，IMNM患者的自身抗体被彻底消除；2名SSc患者的重要器官纤维化损伤均得到了逆转，并在6个月的监测期内持续改善。全球新药研发进展详情（部分） 04 全球医药交易事件本次统计周期（2024.07.13-07.19）全球（含中国）医药交易时间共计43起，涉及药物权益转让、公司并购等多起交易事件。全球医药交易时间汇总表（部分）国内药物批准/研发动态 01 国内新药批准情况根据药渡数据统计分析，本次统计周期（2024.07.13-07.19）国内共有5个新药获NMPA批准上市。其中，NDA批准3个，BLA批准2个。与上次统计周期相比，本次增加3个NMPA批准新药。 7月16日，元羿生物宣布，泽元安®加那索龙（Ganaxolone）口服混悬剂已获得NMPA批准，用于治疗2岁及以上细胞周期蛋白依赖性激酶5（CDKL5）缺乏症患者癫痫发作。其全球III期关键试验主要有效性分析的结果显示，17周的随机双盲安慰剂对照研究中加那索龙组28天主要运动性癫痫发作频率相对于基线的下降百分比为30.7%。一项2年长期开放性研究结果显示，使用加那索龙的患者中，30~50%患者癫痫发作频次下降≥50%，近10%的患者实现了3个月内无发作。 7月19日，微芯生物收到NMPA正式批准PPAR全激动剂西格列他钠联合二甲双胍用于治疗2型糖尿病的上市申请。西格列他钠通过提高糖尿病患者对胰岛素的敏感性、调节血糖，改善其所并发的脂质代谢紊乱，潜在降低心血管并发症的发生及其危害程度，带来更好的疗效和安全性，实现对糖尿病及其并发症的综合治疗，联合二甲双胍可更好地实现持续降糖、调节血脂和降低心血管风险等多方面临床获益。中国新药批准情况（部分） 02 国内新药临床默示许可进展根据药渡数据统计分析，本次统计周期（2024.07.13-07.16）国内共有18个新药获临床默示许可，涉及28个受理号。其中，化学药8个，治疗用生物制品9个，预防用生物制品1个。与上个统计周期相比，本次减少2个临床默示许可获批受理号。本周国内新药临床默示许可进展（部分） 03 国内新药申报进展根据药渡数据统计分析，本次统计周期（2024.07.13-07.19）国内共有17个新药申报上市，涉及29个受理号。其中，化药7个，治疗用生物制品10个。与上个统计周期相比，本次增加24个新药申报上市受理号。国内新药申报上市情况（部分）根据药渡数据统计分析，本次统计周期（2024.07.13-07.19）国内共有35个新药申报临床，涉及47个受理号。其中，化学药14个，治疗用生物制品18个，预防用生物制品3个。与上个统计周期相比，本次减少48个临床申报受理号。国内新药临床申报情况（部分）根据药渡数据统计分析，本次统计周期（2024.07.13-07.19）国内无药物获NMPA特殊资格认定。 04 国内新药研发进展根据药渡数据统计分析，本次统计周期（2024.07.13-07.19）国内新药临床研发状态无更新。 05 国内新药研发领域政策法规动态关于公开征求《疫苗佐剂非临床研究技术指导原则（征求意见稿）》意见的通知为更好地指导疫苗佐剂非临床研究和评价，促进新型佐剂以及创新佐剂疫苗的研发，经广泛调研和讨论，我中心组织起草了《疫苗佐剂非临床研究技术指导原则（征求意见稿）》。我们诚挚地欢迎社会各界对征求意见稿提出宝贵意见和建议，并及时反馈给我们，以便后续完善。征求意见时限为自发布之日起1个月。 06 国内新药研发领域热点新闻逆势上涨的医药“黑马” 行情再差，也有“逆行者”。今年上半年，医药板块下跌了21.09%，严重跑输大盘（沪深300上涨了0.89%）。但也不乏逆势上涨的药企，比如占据涨幅榜前三的诺泰生物、川宁生物、艾力斯。值得一提的是，这些“逆行者”都有一个共同点，就是基本面靓丽。这说明，在行情不好时，资本市场更看重企业的基本面，也就是公司的内在价值、财务状况、业务模式、市场竞争力等核心要素。这也是投资者在市场波动中寻求稳定回报和长期价值的必然选择。更多资讯，请阅读原文下半年，国产创新药将有哪些“爆点”？上半年的中国制药业，不客气地讲，十分令人失望，CXO全线溃败、创新药半死不活、中药苦苦支撑。反应在资本市场方面，便是股价没有最低只有更低，一路向下头也不回。造成这一局面有多方面的因素，行业周期、新冠后遗症、地缘政治的影响等等。但归根结底，还是中国制药业的内生动力不足。下半年，能否有惊喜？更多资讯，请阅读原文自免领域：口服小分子创新药崭露头角目前，治疗自身免疫疾病的核心药物包括三大类：改善病情抗风湿药、非甾体抗炎药、甾体抗炎药等传统小分子药物；大分子生物制剂和小分子靶向药。生物制剂正在取代传统抗炎药物，成为自免疾病领域的主流治疗方案。然而，自免生物制剂仍存在诸多不足：生物制剂多采用静脉或皮下注射方式递送，降低了患者对治疗的顺应性和依从性；长期用药经济负担较大。在此背景下，口服小分子靶向药应用而生。目前，已有一批自免小分子候选药在临床后期阶段取得了积极的疗效数据，未来，口服小分子自免创新药有望凭借用药便利性和差异化疗效获得可观的市场份额。更多资讯，请阅读原文先声药业第四代抗失眠药国内申报上市今日（7月16日），国家药品监督管理局药品审评中心（CDE）官网公示，先声药业与Idorsia公司联合申报的抗失眠药物盐酸达利雷生（Daridorexant）片的上市申请获CDE受理。从药渡数据检索可知，达利雷生是一款双食欲素受体（OX1和OX2）拮抗剂，2022年1月获FDA批准上市。食欲素受体拮抗剂是第四代抗失眠药物，与传统催眠药相比，食欲素拮抗剂具有较少的副作用，记忆障碍和依赖潜力较小。研究表明白天给予食欲素激动剂能够促进清醒，而夜间给予食欲素受体拮抗剂可以促进睡眠。 2022年11月先声药业与Idorsia公司就达利雷生在中国的开发签订独家许可协议，根据协议……更多资讯，请阅读原文国内首款IL-17A/IL-17F抗体药物获批上市 7月19日，NMPA官网公示优时比公司申报的白细胞介素17A（IL-17A）和白细胞介素17F（IL-17F）生物制剂比奇珠单抗（Bimekizumab）获批上市，这也是国内首款获批上市的IL-17A/IL-17F单抗。白细胞介素-17（IL-17）家族包括六个成员（IL-17A-17F），其中IL-17A和IL-17F在氨基酸序列上相似度高达50%，可以形成异二聚体。IL-17A/IL-17F由Th17、CD8+ T、γδT、NKT、NK、ILC3等细胞产生，IL-17A/IL-17F与疾病的研究目前集中在自身免疫病与炎症性疾病，如银屑病、多发性硬化、炎症性肠病、肿瘤等领域。比奇珠单抗是一款人源化单克隆IgG1抗体，可选择性抑制IL-17A、IL-17F和IL-17A/F异二聚体……更多资讯，请阅读原文咨询、合作请联系作者小D有话说为方便读者阅读及保存，我们将周报原文整理成了PDF版本，如需获取全文，可点击最上方蓝字，在药渡Daily公众号后台回复“0726创新药周报”，即可下载。

上市批准申请上市

2024-07-17

·Pharmaceutical Technology

FDA issues CRL to Orexo’s NDA for opioid overdose medication

In September last year, the company submitted the NDA to the FDA seeking approval for the product. Credit: luchschenF / Shutterstock. The US Food and Drug Administration (FDA) has issued a complete response letter (CRL) to Orexo regarding a new drug application (NDA) for its high-dose naloxone rescue medication, OX124, designed to counteract opioid overdoses. The company submitted the NDA to the FDA in September 2023. The US regulator is seeking an additional human factors (HF) study, consistent with prior communications. Further technical data on the final commercial product was also sought by the FDA, with no additional clinical or non-clinical studies needed. The company has already conducted a new HF study to comply with the FDA’s requirements. However, the request for additional technical data on commercial-scale manufacturing was not anticipated. See Also: Sumitomo Pharma’s DSP-5336 gains FDA fast track for AML AstraZeneca completes Amolyt Pharma acquisition Orexo will now work with the FDA to provide the necessary information and aims to resubmit the NDA promptly. The FDA’s review following resubmission could take up to six months. Orexo states that the technical data required by the FDA was generated during pilot-scale production and included in the initial NDA. However, the FDA has sought data from established commercial-scale manufacturing. Once approved, OX124 is expected to address the need for medications and higher naloxone dosages, especially due to the prevalence of synthetic opioids such as fentanyl, which are implicated in 92% of all fatal opioid overdoses. OX124’s formulation is designed for quick absorption and increased bioavailability, to reverse the effects of synthetic opioid overdose. Orexo president and CEO Nikolaj Sørensen stated: “I am impressed by the vigour and agility of the teams in Sweden and the US in addressing the FDA’s concerns from April regarding the instructions for use and our ability to complete a new human factors study shortly. However, I am surprised by the agency´s other requests with regard to additional technical data from the final commercial product, but confident we can address this efficiently. “We remain confident that our powerful life-saving medication, OX124, can contribute to reducing the steep number of Americans who die from overdoses caused by the increasingly prevalent synthetic opioids.”

申请上市快速通道

2024-07-17

·Pharmaceutical Technology

CatalYm secures $150m to advance GDF-15-targeting immune modulator

This $150m funding round builds on a $51m Series C round in November 2022. Credit: ma_Design via Shutterstock. German cancer biotech CatalYm has secured $150m in a Series D funding round following the recently announced data for its lead monoclonal antibody visugromab. The company has centred its pipeline on drugs targeting GDF-15 or growth differentiation factor-15, which acts as a key regulator of immune resistance to cancer therapies. The company was in the news earlier this year, when it shared follow-up data of its drug visugromab showing efficacy in heavily pretreated patients. The new funding, led by Canaan Partners and Bioqube Ventures, is set to fund the company’s planned Phase IIb trial of visugromab in select checkpoint-naïve front-line and second-line treatment settings. The drug has so far been studied in combination with Bristol Myers Squibb’s (BMS) anti-PD-1 drug Opdivo (nivolumab) in patients with non-squamous non-small cell lung cancer (NSCLC), hepatocellular cancer, and urothelial cancer. CatalYm presented data from the ongoing GDFATHER Phase I/IIa trial (NCT04725474) that is testing this combination at the American Society of Clinical Oncology (ASCO) meeting held in Chicago, on 2 June. Across all tumour types, patients who received visugromab showed an objective response rate of 16.7%. The average duration of response surpassed 15 months for NSCLC, and 14 months for urothelial cancer, with 77% of the patients’ responses still ongoing. These 90 patients were heavily pretreated and had experienced failed anti-PD-1 therapies in the past. See Also: Sumitomo Pharma’s DSP-5336 gains FDA fast track for AML AstraZeneca completes Amolyt Pharma acquisition Anti PD-1 checkpoint inhibitor drugs, such as BMS’ Opdivo, enhance the immune system’s ability to fight cancer by blocking the PD-1 receptor on T cells, a checkpoint that normally helps keep immune responses in check. Cancer cells often exploit this pathway to avoid being attacked by the immune system. Elevated GDF-15 levels in cancers can cause anti-PD-1 drugs to fail by creating an immunosuppressive tumour environment that hinders T cell activation and recruitment, which visugromab is designed to target. Checkpoint inhibitors have pulled in billions over the last few years. MSD’s PD-1 checkpoint inhibitor Keytruda (pembrolizumab) was the world’s top-selling drug last year, making $25bn. BMS’ Opdivo generated $9bn in the same year, as per the company financials. One of the reasons for the high sales is the drugs’ ability to be paired with other anti-cancer medicines. In the announcement accompanying the funding, CatalYm’s CEO Phil L’Huillier said: “We continue to demonstrate visugromab’s potential to induce cancer remission depth and durability across multiple solid tumour indications, emphasising the substantial role that visugromab could play in a novel anti-cancer therapy regimen.”

免疫疗法ASCO会议临床2期临床结果并购

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适应症	最高研发状态	国家/地区	公司	日期
急性淋巴细胞白血病	临床2期	美国	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	日本	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	比利时	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	加拿大	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	法国	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	意大利	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	新加坡	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	韩国	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	西班牙	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	中国台湾	Sumitomo Pharma America, Inc.	2022-02-28

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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


NCT04988555 (EHA2024) 人工标引	临床1/2期	急性白血病 NPM1 Mutation \| KMT2A Rearrangement	58	DSP-5336	廠製淵觸鏇醖鬱憲鑰淵(鑰鏇齋壓積壓艱鹹齋壓) = 夢齋鬱範繭積醖醖範獵願窪醖選鏇鬱鏇鑰製窪 (壓餘憲觸願艱獵鹽簾繭 ) 更多	积极	2024-05-14
NCT04988555 (ASH2023) 人工标引	临床1/2期	复发性急性白血病 \| 难治性急性白血病	24	DSP-5336±concomitant azole therapy	鏇壓鹽製鹹醖襯壓壓鏇(鑰憲襯鹹衊鹽夢糧構憲) = 鏇鏇積鑰選憲淵窪製鑰膚艱衊簾製蓋壓獵衊鑰 (襯鬱鏇積積獵觸窪顧製 ) 更多	积极	2023-12-10
NCT04988555 (ASH2023) 人工标引	临床1/2期	复发性急性白血病 \| 难治性急性白血病	24	DSP-5336±concomitant azole therapy (NPM1c)	網艱鬱範衊鑰積範鹽簾(鹹衊積鑰遞遞獵遞鹹選) = 網夢餘齋製廠製網淵鏇艱蓋醖網廠觸願膚廠鏇 (顧醖觸遞選鑰鹹蓋鑰願 )	积极	2023-12-10