Olutasidenib induced durable composite complete remission in 43.8% of patients relapsed or refractory to prior venetoclax-based regimens

在43.8%的复发或难治于先前基于venetoclax的方案的患者中，Olutasidenib诱导了持久的复合完全缓解

Safety was consistent with the overall profile of olutasidenib

安全性与olutasidenib的总体概况一致

Olutasidenib may offer a valuable treatment option for patients with mIDH1 previously treated with venetoclax

Olutasidenib可能为先前接受venetoclax治疗的mIDH1患者提供有价值的治疗选择

SOUTH SAN FRANCISCO, Calif., April 4, 2024 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today announced a peer-reviewed publication in Leukemia & Lymphoma on data from an analysis of the Phase 2 study evaluating REZLIDHIA® (olutasidenib), a potent, selective, oral, small-molecule inhibitor of mutant isocitrate dehydrogenase-1 (mIDH1)1, in patients with mIDH1 acute myeloid leukemia (AML) who were relapsed/refractory (R/R) to prior venetoclax-based regimens..

加利福尼亚州南旧金山，2024年4月4日/PRNewswire/--Rigel Pharmaceuticals，Inc.（纳斯达克：RIGL）今天宣布了一份同行评审的《白血病与淋巴瘤》出版物，该出版物的数据来自对2期研究的分析，该研究评估了REZLIDHIA®（olutasidenib），一种有效的，选择性的，口服的突变型异柠檬酸脱氢酶-1（mIDH1）1小分子抑制剂，用于先前基于venetoclax的方案复发/难治性（R/R）的mIDH1急性髓性白血病（AML）患者。。

'Venetoclax in combination with a hypomethylating agent is currently standard treatment for patients with newly diagnosed AML who are unfit for intensive chemotherapy, including those with mIDH1. When this therapy fails, patients historically have had limited treatment options and poor prognoses,' said Jorge E.

“Venetoclax联合低甲基化药物目前是新诊断的AML患者的标准治疗方法，这些患者不适合进行强化化疗，包括mIDH1患者。当这种疗法失败时，患者历史上的治疗选择有限，预后不佳。

Cortes, M.D., Director, Georgia Cancer Center, Cecil F. Whitaker Jr., GRA Eminent Scholar Chair in Cancer, and Phase 2 trial investigator. 'The findings from these analyses suggest that REZLIDHIA may provide an effective treatment for patients with AML following failure of venetoclax combination therapy.

医学博士科尔特斯（Cortes），佐治亚州癌症中心主任，小塞西尔·惠特克（CecilF.Whitaker Jr.），GRA癌症知名学者主席和2期试验研究者。”这些分析的结果表明，雷兹利迪亚可能为venetoclax联合治疗失败后的AML患者提供有效的治疗。

REZLIDHIA induced durable remissions consistent with those observed in the pivotal trial and had a favorable tolerability profile in this challenging to treat patient population, representing a valuable treatment option.'.

REZLIDHIA诱导的持久缓解与关键试验中观察到的一致，并且在这个具有挑战性的治疗患者群体中具有良好的耐受性，代表了一种有价值的治疗选择。”。

'These data support REZLIDHIA's efficacy and well-characterized safety profile in patients with mIDH1 R/R AML who had previously been treated with venetoclax combination regimens,' said Raul Rodriguez, Rigel's president and CEO. 'These analyses are important because they provide valuable insights into the potential benefit of REZLIDHIA in different segments of the mIDH1 R/R AML patient population.'.

Rigel总裁兼首席执行官劳尔·罗德里格斯（RaulRodriguez）说：“这些数据支持REZLIDHIA对先前接受过venetoclax联合方案治疗的mIDH1 R/R AML患者的疗效和良好的安全性。”这些分析很重要，因为它们为REZLIDHIA在mIDH1 R/R AML患者人群的不同部分中的潜在益处提供了有价值的见解。”。

Key points from the paper are summarized below:

本文的要点总结如下：

Olutasidenib alone or in combination with azacitidine demonstrated potential efficacy in patients with AML following failure of venetoclax combination therapy

单独使用或与阿扎胞苷联合使用的Olutasidenib在venetoclax联合治疗失败后对AML患者显示出潜在的疗效

Of the 18 patients with prior venetoclax treatment, 10 were relapsed, 6 were refractory, and 2 had complete remission with incomplete hematologic recovery (CRi) to a venetoclax combination

在18例接受过venetoclax治疗的患者中，10例复发，6例难治，2例完全缓解，血液学恢复不完全

Of the 16 R/R patients, 7 (43.8%) achieved a composite complete remission (CRc), 4 (25%) achieved complete remission (CR), and 1 (6.3%) achieved CR with partial hematologic recovery (CRh). Both patients with CRi at study entry achieved CR

在16例R/R患者中，7例（43.8%）达到复合完全缓解（CRc），4例（25%）达到完全缓解（CR），1例（6.3%）达到部分血液学恢复（CRh）的CR。两名CRi患者在研究开始时均达到CR

Median time to CRc was 1.9 months (range 1-2.8). As of the data cut-off (June 18, 2021), median duration of CRc was not reached (range, 1.2-NR, ongoing at 30.4+ months)

CRc的中位时间为1.9个月（范围1-2.8）。截至数据截止日期（2021年6月18日），尚未达到CRc的中位持续时间（范围为1.2-NR，持续时间为30.4个月以上）

Red blood cell and platelet transfusion independence was achieved in 2/12 (17%) and 2/7 (29%) transfusion-dependent R/R patients at baseline, respectively

基线时，分别有2/12（17%）和2/7（29%）输血依赖的R/R患者实现了红细胞和血小板输注的独立性

Safety was consistent with the overall profile of olutasidenib

安全性与olutasidenib的总体概况一致

The paper, titled 'Olutasidenib in post-venetoclax patients with mutant isocitrate dehydrogenase 1 (mIDH1) acute myeloid leukemia (AML),' was published online in Leukemia & Lymphoma and can be accessed here.

这篇题为“突变型异柠檬酸脱氢酶1（mIDH1）急性髓性白血病（AML）的venetoclax后患者中的Olutasidenib”的论文在线发表在《白血病与淋巴瘤》杂志上，可在此处访问。

About AML

关于反洗钱

Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that there will be about 20,800 new cases in the United States, most in adults, in 2024.2.

急性骨髓性白血病（AML）是一种快速发展的血液和骨髓癌症，会影响骨髓细胞，骨髓细胞通常会发育成各种类型的成熟血细胞。AML主要发生在成人中，约占所有成人癌症的1%。美国癌症协会估计，到2024年，美国将有约20800例新病例，其中大多数是成年人。

Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.3 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.4 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need..

复发性AML影响大约一半的患者，这些患者在治疗和缓解后，骨髓中的白血病细胞会恢复。难治性AML影响10%至40%的新诊断患者，当患者即使在强化治疗后也无法达到缓解时，就会发生难治性AML。4连续接受AML治疗的患者的生活质量下降，复发或难治性疾病的耐受性良好的治疗仍然是一个未得到满足的需求。。

About REZLIDHIA®

关于REZLIDHIA®

INDICATION

指示

REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

REZLIDHIA适用于治疗成人复发或难治性急性髓细胞白血病（AML）患者，该患者通过FDA批准的测试检测到易感异柠檬酸脱氢酶-1（IDH1）突变。

IMPORTANT SAFETY INFORMATION

重要安全信息

WARNING: DIFFERENTIATION SYNDROME

警告：辨证

Differentiation syndrome, which can be fatal, can occur with REZLIDHIA treatment. Symptoms may include dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain. If differentiation syndrome is suspected, withhold REZLIDHIA and initiate treatment with corticosteroids and hemodynamic monitoring until symptom resolution..

REZLIDHIA治疗可能会发生致命的分化综合征。症状可能包括呼吸困难，肺部浸润/胸膜心包积液，肾损伤，低血压，发烧和体重增加。如果怀疑有分化综合征，则停止使用REZLIDHIA，并开始使用皮质类固醇和血流动力学监测进行治疗，直到症状消失。。

WARNINGS AND PRECAUTIONS

警告和注意事项

Differentiation Syndrome

辨证论治

REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal.

REZLIDHIA可引起分化综合征。在复发或难治性AML患者的REZLIDHIA临床试验中，分化综合征发生率为16%，3或4级分化综合征发生率为8%，死亡率为1%。分化综合征与骨髓细胞的快速增殖和分化有关，可能危及生命或致命。

Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption of REZLIDHIA.

REZLIDHIA治疗患者的辨证症状包括白细胞增多，呼吸困难，肺浸润/胸膜心包积液，肾损伤，发热，水肿，发热和体重增加。在经历分化综合征的25例患者中，19例（76%）在治疗后或雷兹利迪亚剂量中断后恢复。

Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis..

分化综合征最早发生在REZLIDHIA发作后1天至18个月，并且已经观察到伴有或不伴有白细胞增多症。。

If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated.

如果怀疑有分化综合征，则暂时停止服用REZLIDHIA并开始使用全身皮质类固醇（例如，每12小时静脉注射地塞米松10 mg），持续至少3天，直到体征和症状消失。如果观察到伴随的白细胞增多，请按照临床指示开始用羟基脲治疗。

Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence..

症状缓解后减少皮质类固醇和羟基脲。分化综合征可能会因过早停用皮质类固醇和/或羟基脲治疗而复发。制定支持措施和血流动力学监测直至改善；保留REZLIDHIA的剂量，并考虑根据复发减少剂量。。

Hepatotoxicity

肝毒性

REZLIDHIA can cause hepatotoxicity, presenting as increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13% experienced grade 3 or 4 hepatotoxicity.

REZLIDHIA可引起肝毒性，表现为丙氨酸氨基转移酶（ALT）升高，天冬氨酸氨基转移酶（AST）升高，血液碱性磷酸酶升高和/或胆红素升高。153例接受REZLIDHIA治疗的复发或难治性AML患者中，23%的患者发生肝毒性；13%经历了3级或4级肝毒性。

One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury. The median time to onset of hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months).

在临床试验中，一名接受雷兹利迪亚联合阿扎胞苷治疗的患者因药物性肝损伤并发症死亡，该联合治疗未显示雷兹利迪亚。REZLIDHIA治疗复发或难治性AML患者肝毒性发作的中位时间为REZLIDHIA开始后1.2个月（范围：1天至17.5个月），中位缓解时间为12天（范围：1天至17个月）。

The most common hepatotoxicities were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin. Monitor patients frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Obtain baseline liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once in the fourth month, and once every other month for the duration of therapy.

最常见的肝毒性是ALT，AST，血液碱性磷酸酶和血液胆红素升高。经常监测患者肝功能障碍的临床症状，如疲劳，厌食，右上腹部不适，尿黑或黄疸。在开始REZLIDHIA之前，至少在前两个月每周进行一次基线肝功能检查，在第三个月每隔一周进行一次，在第四个月进行一次，在治疗期间每隔一个月进行一次。

If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue REZLIDHIA based on recurrence/severity..

如果发生肝功能障碍，则根据复发/严重程度停止，减少或永久停止REZLIDHIA。。

ADVERSE REACTIONS

不良反应

The most common (≥20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis..

包括实验室异常在内的最常见（≥20%）不良反应是天冬氨酸转氨酶升高，丙氨酸转氨酶升高，钾降低，钠降低，碱性磷酸酶升高，恶心，肌酐升高，疲劳/不适，关节痛，便秘，淋巴细胞增加，胆红素升高，白细胞增多，尿酸升高，呼吸困难，发热，皮疹，脂肪酶升高，粘膜炎，腹泻和转氨酶。。

DRUG INTERACTIONS

药物相互作用

Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers.

避免将REZLIDHIA与强或中度CYP3A诱导剂同时使用。

Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless otherwise instructed in the substrates prescribing information. If concomitant use is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

除非底物处方信息中另有说明，否则避免将REZLIDHIA与敏感的CYP3A底物同时使用。如果不可避免地同时使用，请监测患者这些药物治疗效果的丧失。

LACTATION

哺乳期

Advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose.

建议女性在服用REZLIDHIA期间和最后一次服用后2周内不要母乳喂养。

GERIATRIC USE

老年使用

No overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase in incidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age.

在65岁以上和年轻患者之间，没有观察到总体有效性差异。与65岁以下的患者相比，≥65岁的患者肝毒性和高血压的发生率增加。

HEPATIC IMPAIRMENT

肝功能损害

In patients with mild or moderate hepatic impairment, closely monitor for increased probability of differentiation syndrome.

对于轻度或中度肝功能损害的患者，密切监测分化综合征的可能性增加。

Click here for Full Prescribing Information, including Boxed WARNING.

单击此处查看完整的处方信息，包括盒装警告。

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

要向FDA报告处方药的副作用，请访问www.FDA.gov/medwatch或致电1-800-FDA-1088（800-332-1088）。

REZLIDHIA is a registered trademark of Rigel Pharmaceuticals, Inc.

REZLIDHIA是Rigel Pharmaceuticals，Inc.的注册商标。

About Rigel

关于线路

Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in South San Francisco, California. For more information on Rigel, the Company's marketed products and pipeline of potential products, visit www.rigel.com..

Rigel Pharmaceuticals，Inc.（纳斯达克股票代码：RIGL）是一家致力于发现、开发和提供新疗法的生物技术公司，可显着改善血液病和癌症患者的生活。里格尔成立于1996年，总部位于加利福尼亚州南旧金山。有关Rigel、该公司已上市产品和潜在产品渠道的更多信息，请访问www.Rigel.com。。

de Botton S, et al. Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML. Blood Advances. February 1, 2023.

de Botton S等人，Olutasidenib（FT-2102）可诱导复发或难治性IDH1突变AML患者持续完全缓解。血液前进。2023年2月1日。

doi: https://doi.org/10.1182/bloodadvances.2022009411

嘿https://doi.org/10.1182/bloodadvances.2022009411

The American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML). Revised January 17, 2024. Accessed Feb. 19, 2024: https://www.cancer.org/cancer/acute-myeloid-leukemia/about/key-statistics.html

美国癌症协会。急性髓细胞白血病（AML）的关键统计数据。2024年1月17日修订。2024年2月19日访问：https://www.cancer.org/cancer/acute-myeloid-leukemia/about/key-statistics.html

Leukaemia Care. Relapse in Acute Myeloid Leukaemia (AML). Version 3. Reviewed October 2021. Accessed Feb 19, 2024: https://media.leukaemiacare.org.uk/wp-content/uploads/Relapse-in-Acute-Myeloid-Leukaemia-AML-Web-Version.pdf

白血病护理。急性髓细胞白血病（AML）的复发。版本3。2021年10月审查。2024年2月19日访问：https://media.leukaemiacare.org.uk/wp-content/uploads/Relapse-in-Acute-Myeloid-Leukaemia-AML-Web-Version.pdf

Thol F, Schlenk RF, Heuser M, Ganser A. How I treat refractory and early relapsed acute myeloid leukemia. Blood (2015) 126 (3): 319-27. doi: https://doi.org/10.1182/blood-2014-10-551911

Thol F，Schlenk RF，Heuser M，Ganser A.我如何治疗难治性和早期复发的急性髓细胞白血病。Blood（2015）126（3）：319-27。内政部：https://doi.org/10.1182/blood-2014-10-551911

Forward-Looking Statements

前瞻性声明

This press release contains forward-looking statements relating to, among other things, that olutasidenib may provide a meaningful approach to the treatment of Post-Venetoclax Patients with Mutant IDH1 AML. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements.

本新闻稿包含前瞻性声明，其中涉及到olutasidenib可能为治疗患有突变IDH1 AML的Venetoclax后患者提供有意义的方法。本新闻稿中包含的任何不属于历史事实声明的声明都可能被视为前瞻性声明。

Forward-looking statements can be identified by words such as 'may', 'potential', 'look forward', 'believe', 'will' and similar expressions in reference to future periods. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Rigel's current beliefs, expectations, and assumptions and hence they inherently involve significant risks, uncertainties and changes in circumstances that are difficult to predict and many of which are outside of our control.

前瞻性陈述可以用“可能”、“潜在”、“展望”、“相信”、“将会”等词语以及与未来时期相关的类似表达来识别。前瞻性陈述既不是历史事实，也不是未来表现的保证。相反，它们是基于里格尔目前的信念、期望和假设，因此它们固有地涉及难以预测的重大风险、不确定性和环境变化，其中许多超出了我们的控制范围。

Therefore, you should not rely on any of these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the FDA, European Medicines Agency, PMDA or other regulatory authorities may make adverse decisions regarding olutasidenib; risks that clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that olutasidenib may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop Rigel's product candidates; market competition; as well as other risks detailed from time to time in Rigel's reports filed with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended Decembe.

因此，您不应该依赖这些前瞻性陈述。由于这些风险和不确定性，实际结果和事件发生的时间可能与此类前瞻性声明中的预期有很大不同，这些风险和不确定性包括但不限于与FDA、欧洲药品管理局、PMDA或其他监管机构相关的风险和不确定性，可能会对奥拉西德尼做出不利决定；临床试验可能无法预测实际结果或后续临床试验结果的风险；olutasidenib可能产生意外副作用，不良反应或误用事件的风险；开发Rigel候选产品的资源可用性；市场竞争；以及Rigel向美国证券交易委员会提交的报告中不时详述的其他风险，包括截至12月底的10-K表年度报告。

Contact for Investors & Media:

投资者和媒体联系人：

Investors:

投资者：

Rigel Pharmaceuticals, Inc.

Rigel Pharmaceuticals，股份有限公司。

650.624.1232

650.624.1232

ir@rigel.com

ir@rigel.com

Media:

媒体：

David Rosen

戴维·罗森

Argot Partners

Argot合作伙伴

212.600.1902

212.600.1902

david.rosen@argotpartners.com

david.rosen@argotpartners.com

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SOURCE Rigel Pharmaceuticals, Inc.

来源Rigel Pharmaceuticals，Inc。

Company Codes: NASDAQ-NMS:RIGL

公司代码：NASDAQ-NMS：RIGL