Azacitidine

▎药明康德内容团队报道 今日（3月25日），中国国家药监局药品审评中心（CDE）官网最新公示，施维雅（Servier）申报的5.1类新药艾伏尼布片的新适应症上市申请已获得受理。公开资料显示，艾伏尼布片（ivosidenib）是一种针对IDH1突变酶的口服靶向抑制剂。该产品此前已作为“临床急需境外新药”获中国NMPA批准，用于治疗携带IDH1易感突变的复发或难治性急性髓系白血病（AML）成人患者。 根据中国临床研究进展推测，本次该产品申报上市的适应症可能为联合阿扎胞甘一线治疗携带易感IDH1突变的AML患者。 截图来源：CDE官网 艾伏尼布片是一种针对IDH1突变酶的口服靶向抑制剂。该产品曾获得美国FDA授予快速通道资格、孤儿药资格，并于2018年7月首次获得FDA批准。在中国，该产品于2020年11月被纳入《第三批临床急需境外新药名单》，于2022年1月通过优先审评审批程序附条件获得中国NMPA批准。2024年8月，该产品还入围了2024年盖伦奖候选名单。 在美国，该药目前已获批适用于经FDA批准的试验检测出的携带易感IDH1突变的患者，包括：与阿扎胞苷联用或单药治疗75岁或以上或有合并症不能使用强化诱导化疗的成人新诊断的AML；单药治疗复发或难治性AML成人患者；治疗复发或难治性骨髓增生异常综合征（MDS）成人患者；既往接受过治疗的局部晚期或转移性胆管癌成年患者。在中国，艾伏尼布已获批准用于治疗携带易感IDH1突变的成年复发性或难治性AML患者。 根据中国药物临床试验登记与信息公示平台官网，研究人员已经在中国开展了一项3期、随机双盲、安慰剂对照的多中心研究，针对受试者人群为IDH1突变急性髓性白血病且未经治疗的患者，评估与联合使用阿扎胞苷和安慰剂相比，联合艾伏尼布片和阿扎胞苷能否显著延长患者总生存期(OS)。该研究在全球20个国家和地区开展，目前已经完成患者招募。 针对一线治疗携带IDH1突变的AML适应症，艾伏尼布片于2022年获得FDA批准。这一批准得到全球性3期临床试验AGILE数据的支持。这是一项全球3期、多中心、双盲、随机、安慰剂对照临床试验，研究结果已在《新英格兰医学杂志》上发表。 试验结果显示，与化疗相比，艾伏尼布与阿扎胞苷联用，显著改善了患者的无事件生存期（EFS）。艾伏尼布与阿扎胞苷联用，显示出总生存期（OS）的统计学显著改善，艾伏尼布组中位OS为24.0个月，是对照组（7.9个月）的3倍。此外，艾伏尼布联合阿扎胞苷的完全缓解（CR）率为47.2%，而安慰剂联合阿扎胞苷为14.9%。艾伏尼布联合阿扎胞苷的完全缓解加完全缓解伴部分血液学恢复的缓解率（CR+CRh）为52.8%，而安慰剂联合阿扎胞苷组为17.6%。艾伏尼布联合阿扎胞苷的客观缓解率（ORR）为62.5%，而安慰剂联合阿扎胞苷组为18.9%。 除了上述适应症，施维雅还在评估艾伏尼布片用于其他IDH1突变癌症的应用潜力。今年1月，施维雅宣布了两项3期临床研究进展更新，两项3期研究分别评估艾伏尼布针对IDH1突变型常规软骨肉瘤、特定的IDH1突变型骨髓增生异常综合征患者的疗效和安全性。 参考资料： [1]中国国家药监局药品审评中心（CDE）官网. Retrieved Mar 27，2025, From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c [2]Servier Announces Expansion of its Tibsovo (ivosidenib) Development Program Investigating its Safety and Efficacy in Patients Living with IDH1-Mutated Cancers in Both Hematological Malignancies and Solid Tumors. Retrieved Jan 9，2025, From https://servier.us/blog/servier-announces-expansion-of-its-tibsovo-ivosidenib-development-program-investigating-its-safety-and-efficacy-in-patients-living-with-idh1-mutated-cancers-in-both-hematological-malignancies-and-so/ [3]喜讯！施维雅拓舒沃®入围2024年盖伦奖候选名单.  Retrieved Aug 16，2024, From https://mp.weixin.qq.com/s/oO26302aqMlrJM1-yYICGQ 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。转载授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。 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。

Across two trials, 9 of 10 frontline AML patients achieved remission when treated with mipletamig in combination with the standard of care Triplet Combination with mipletamig continues to outperform doublet combination benchmark No Cytokine Release Syndrome (CRS) has been observed in the RAINIER trial to date Cohort 2 enrollment nears completion SEATTLE, WA / ACCESS Newswire / March 20, 2025 / Aptevo Therapeutics ("Aptevo") (NASDAQ:APVO), a clinical-stage biotechnology company developing novel bispecific immuno-oncology therapeutics based on its proprietary ADAPTIR® and ADAPTIR-FLEX® platform technologies, today announced two additional frontline AML patients have achieved remission* within 30 days of treatment in the Company's RAINIER dose optimization trial evaluating mipletamig in combination with standard of care for patients unfit for intensive chemotherapy. In total, 9 of 10 frontline patients across two trials achieved remission* when receiving the triplet combination of mipletamig + venetoclax + azacitidine (ven/aza). Notably, no CRS has been reported in the RAINIER trial to date. The data builds on previously reported favorable outcomes from RAINIER's Cohort 1 and the completed dose expansion trial where 100% of frontline patients achieved remission. Together with the addition of these interim Cohort 2 results, mipletamig has achieved a compelling overall remission rate of 90% among frontline patients. This outperforms the doublet remission* rate from a venetoclax + azacitidine only study, of 66%. Additionally, the frontline patient triplet therapy CR rate of 70% outperforms the CR rate from a venetoclax + azacitidine only study of 36% (Viale-A Pivotal trial).Thus far, all RAINIER patients who achieved remission remain in remission. Cohort 2 will include six patients, dosed at the 18mcg level, the same dose used in combination with ven/aza in the completed expansion trial. Three patients evaluable for efficacy achieved the following outcomes: Two patients achieved remission withing 30 days of being dosed One patient progressed after the first cycle and passed away for reasons unrelated to study drugs Cohort 2 enrollment is nearing completion Two patients achieved remission withing 30 days of being dosed One patient progressed after the first cycle and passed away for reasons unrelated to study drugs Cohort 2 enrollment is nearing completion "We're now past the halfway mark in Cohort 2 of the RAINIER trial and are thrilled by the continued, highly favorable remission results," said Dirk Huebner, MD, Chief Medical Officer of Aptevo. " This emerging pattern further supports mipletamig's impact on treatment outcomes in frontline AML patients who are not fit for intensive chemotherapy and who would otherwise receive ven/aza as the standard of care. One of our primary goals with the RAINIER trial is to demonstrate the contribution of mipletamig's unique mechanism of action when used in combination with venetoclax and azacitidine. By targeting AML this way, our approach has the potential to improve outcomes, particularly for elderly patients who have limited treatment options." Mipletamig, a differentiated by design CD3 x CD123 bispecific antibody built on Aptevo's ADAPTIR platform and driven by a unique CRIS-7 derived binding domain, is being investigated as frontline therapy in combination with venetoclax and azacitidine, the current standard of care for AML patients who are unfit for intensive chemotherapy. These latest results further reinforce mipletamig's potential as a transformative treatment, supported by impressive efficacy, safety, and tolerability data from two prior clinical trials involving almost 100 patients. *Remission = complete remission (CR) and, complete remission with blood markers that have not yet recovered (CRi). About RAINIER RAINIER, a frontline AML study, is a Phase 1b/2 dose optimization, multi-center, multi-cohort, open label study of up to 39 patients who are being treated across five dose levels ranging from 9 mcg - 140 mcg in combination with venetoclax and azacitidine (ven/aza). Subjects will be adults aged 18 or older, newly diagnosed with AML who are not eligible for intensive induction chemotherapy. Phase 1b consists of 28-day cycles of treatment in five sequential cohorts. Aptevo has partnered with Prometrika (https://www.prometrika.com/), a premier contract research organization for the trial. RAINIER will be conducted in two parts. First, a Phase 1b dose optimization study in frontline AML patients followed by a Phase 2 study. Cohort 1 included 3 patients, dosed at the 9mcg level. All patients achieved remission* within 30 days Thus far, all patients who achieved remission remain in remission. One CR patient had no minimal residual disease (MRD-negative status) and was positive for the TP53 genetic mutation, which is generally associated with poor prognosis due to chemotherapy resistance, genetic instability, and overall treatment challenges All patients achieved remission* within 30 days Thus far, all patients who achieved remission remain in remission. One CR patient had no minimal residual disease (MRD-negative status) and was positive for the TP53 genetic mutation, which is generally associated with poor prognosis due to chemotherapy resistance, genetic instability, and overall treatment challenges About Mipletamig Aptevo's wholly owned lead proprietary drug candidate, mipletamig, targeting AML, MDS and other leukemias, is differentiated by design to redirect the immune system of the patient to destroy leukemic cells and leukemic stem cells expressing the target antigen CD123, which is a compelling target for AML due to its overexpression on leukemic stem cells and AML blasts. This antibody-like recombinant protein therapeutic is designed to engage both leukemic cells and T cells of the immune system and bring them closely together to trigger the destruction of leukemic cells. Mipletamig is purposefully designed to reduce the likelihood and severity of CRS by use of a unique CD3 derived from CRIS-7 vs. the CD3 used by other competitors. Mipletamig has received orphan drug designation ("orphan status") for AML according to the Orphan Drug Act. Mipletamig has been evaluated in almost 100 patients over three trials to date. RAINIER, Aptevo's Phase 1b/2 frontline AML program, was initiated in 3Q24. About Aptevo Therapeutics Aptevo Therapeutics Inc. (NASDAQ:APVO) is a clinical-stage biotechnology company focused on developing novel bispecific immunotherapies for the treatment of cancer. The company has two clinical candidates. Mipletamig is currently being evaluated in RAINIER, a Phase 1b/2 trial for the treatment of frontline acute myeloid leukemia in combination with standard of care venetoclax + azacitidine. Mipletamig has orphan status for AML according to the Orphan Drug Act. ALG.APV-527, a bispecific conditional 4-1BB agonist that is only active upon simultaneous binding to 4-1BB and 5T4, is being co-developed with Alligator Bioscience and is being evaluated in a Phase 1 clinical trial for the treatment of multiple solid tumor types likely to express 5T4. Aptevo has three pre-clinical candidates with different mechanisms of action designed to target a range of solid tumors. All pipeline candidates were created from two proprietary platforms, ADAPTIR® and ADAPTIR-FLEX®. The Aptevo mission is to improve treatment outcomes and transform the lives of cancer patients. For more information, please visit www.aptevotherapeutics.com. Safe Harbor Statement This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical fact, including, without limitation, Aptevo's expectations about the activity, efficacy, safety, tolerability and durability of its therapeutic candidates and potential use of any such candidates, including in combination with other drugs, as therapeutics for treatment of disease, its expectations regarding the effectiveness of its ADAPTIR and ADAPTIR-FLEX platforms, statements related to the progress of Aptevo's clinical programs, including statements related to anticipated clinical and regulatory milestones, whether further study of mipletamig in a Phase 1b dose optimization trial focusing on multiple doses of mipletamig in combination with venetoclax + azacitidine on a targeted patient population will continue to show remissions, whether Aptevo's final remission data or trial results will vary from its earlier assessment, whether Aptevo's strategy will translate into an improved overall survival in AML, especially among patient subgroups with poor prognosis, whether further study of ALG.APV-527 across multiple tumor types will continue to show clinical benefit, the possibility and timing of future preliminary or interim data readouts for ALG.APV-527, statements related to the progress of and enthusiasm for Aptevo's clinical programs, statements related to Aptevo's ability to generate stockholder value, whether Aptevo will continue to have momentum in its business in the future, and any other statements containing the words "may," "continue to," "believes," "knows," "expects," "optimism," "potential," "designed," "promising," "plans," "will" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based on Aptevo's current intentions, beliefs, and expectations regarding future events. Aptevo cannot guarantee that any forward-looking statement will be accurate. Investors should realize that if underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could differ materially from Aptevo's expectations. Investors are, therefore, cautioned not to place undue reliance on any forward-looking statement. There are several important factors that could cause Aptevo's actual results to differ materially from those indicated by such forward-looking statements, including a deterioration in Aptevo's business or prospects; further assessment of preliminary or interim data or different results from later clinical trials; adverse events and unanticipated problems, adverse developments in clinical development, including unexpected safety issues observed during a clinical trial; and changes in regulatory, social, macroeconomic and political conditions. For instance, actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the uncertainties inherent in the results of preliminary or interim data and preclinical studies being predictive of the results of later-stage clinical trials, initiation, enrollment and maintenance of patients, and the completion of clinical trials, the availability and timing of data from ongoing clinical trials, the trial design includes combination therapies that may make it difficult to accurately ascertain the benefits of mipletamig, expectations for the timing and steps required in the regulatory review process, expectations for regulatory approvals, the impact of competitive products, our ability to enter into agreements with strategic partners or raise funds on acceptable terms or at all and other matters that could affect the availability or commercial potential of Aptevo's product candidates, business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises such as the coronavirus (referred to as COVID-19), geopolitical risks, including the current war between Russia and Ukraine, war between Israel and Hamas, and macroeconomic conditions such as economic uncertainty, rising inflation and interest rates, continued market volatility and decreased consumer confidence. These risks are not exhaustive, Aptevo faces known and unknown risks. Additional risks and factors that may affect results are set forth in Aptevo's filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2024, and its subsequent reports on Form 10-Q and current reports on Form 8-K. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from Aptevo's expectations in any forward-looking statement. Any forward-looking statement speaks only as of the date of this press release, and, except as required by law, Aptevo does not assume any obligation to update any forward-looking statement to reflect new information, events, or circumstances. Aptevo Therapeutics Miriam Weber Miller Aptevo Therapeutics IR@apvo.com or millerm@apvo.com +1 (206) 859 6629 SOURCE: Aptevo Therapeutics