Riluzole

Results from this analysis were published in Muscle and Nerve JERSEY CITY, N.J., Aug. 19, 2025 /PRNewswire/ -- Mitsubishi Tanabe Pharma America, Inc. (MTPA) today announced the publication of a retrospective analysis of patients living with amyotrophic lateral sclerosis (ALS) in Muscle and Nerve. The analysis evaluated patients taking RADICAVA ORS® (edaravone) compared with Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) historical placebo controls (patients who did not receive active investigational treatment, but may have received riluzole in their respective clinical trials), with evidence suggesting treatment with RADICAVA ORS decreased physical functional decline and offering insights into survival outcomes. "These findings contribute to the ongoing effort to address unmet needs in ALS treatment by providing insight into the benefits observed with RADICAVA ORS," said Gustavo A. Suarez Zambrano, M.D., Vice President of Medical Affairs at MTPA. "By publishing this analysis, we aim to deliver meaningful insights for healthcare providers, patients and caregivers." The primary analysis, based on data from clinical studies MT-1186-A02/A04, evaluated long-term survival and functional outcomes of 78 propensity score-matched patients treated with RADICAVA ORS compared to 78 matched historical placebo controls from the PRO-ACT database. The main statistical comparison was made between the Combined (FDA approved On/Off + investigational Once Daily) RADICAVA ORS versus PRO-ACT placebo group. The post-hoc analysis, based on data from clinical studies MT-1186-A01/A02/A03/A04, expanded the evaluation to a broader ALS population (n=210 RADICAVA ORS patients vs. 210 PRO-ACT placebo patients) to confirm robustness of the initial results. Propensity score matching on 10 baseline variables was used to assess the impact of RADICAVA ORS suspension on function and survival. The analysis showed evidence for a slowing of functional decline and improved survival outcomes with long-term RADICAVA ORS treatment versus PRO-ACT placebo group patients with ALS. The analysis also showed a smaller ALS Functional Rating Scale-Revised (ALSFRS-R) change from baseline, demonstrating a slower rate of functional decline observed over 48 weeks. Key findings from the analysis include: An association was observed between treatment with RADICAVA ORS and improved survival outcomes compared to matched historical placebo patients in the PRO-ACT database. In the primary analysis cohort, the combined RADICAVA ORS group demonstrated a survival benefit vs the PRO-ACT placebo group over approximately 22 months (P=0.005). Three out of the 78 patients (3.8%) died in the RADICAVA ORS group vs 14/78 (17.9%) in the PRO-ACT placebo group. The baseline risk-adjusted hazard ratio showed an 84% decreased risk of death, indicating a longer survival time, in the combined RADICAVA ORS vs PRO-ACT placebo groups (P=0.005). Additionally, positive trends favoring both the Once Daily (n=65) and On/Off RADICAVA ORS (n=65) groups vs PRO-ACT placebo group (n=65) were observed for number of deaths and time to death, but neither one reached statistical significance. In the post hoc broader ALS cohort, patients from studies MT-1186-A01/A02/A03/A04 showed a difference in time to death over approximately 35 months (P<0.001) Additionally, a post hoc covariate-adjusted restricted mean survival time (RMST) analysis to confirm the average survival time over approximately 34 months showed a mean prolongation of 7.3 months in survival (On/Off and Once Daily RADICAVA ORS: 29.6 months; PRO-ACT placebo group: 22.2 months; P<0.001). The proportion of events in the RADICAVA ORS suspension group (29/210 patients, 13.8%) was significantly smaller than the PRO-ACT placebo group (69/210 patients, 32.9%). RMST is a metric that estimates the average time a group survives relative to a comparator. Over 48 weeks, treatment with RADICAVA ORS was associated with a slower rate of decline in ALSFRS-R scores, suggesting potential benefit in maintaining physical function compared to matched PRO-ACT placebo group. In the primary analysis cohort, patients in both groups had a mean baseline ALSFRS-R score of 41.0 points. The least squares (LS) mean change from baseline to week 48 was −8.4 ± 1.0 points for RADICAVA ORS compared to −14.1 ± 1.0 points for PRO-ACT placebo patients, a difference of 5.6 points (95% CI, 2.8–8.4; P<0.001). In the broader post-hoc cohort, the LS mean change was −10.5 ± 0.7 points for RADICAVA ORS compared to −12.9 ± 0.6 points for PRO-ACT placebo patients, a difference of 2.4 points (95% CI, 0.6–4.2; P=0.008). Lastly, it is important to note that results from this analysis are not generalizable and cannot be used to determine definitive conclusions about the effects of treatment. The p-values are nominal as no multiplicity adjustments were made for these analyzed data. Additionally, this was a non-randomized analysis, and results should be interpreted with caution. Please see publication for additional limitations. "There remains no cure for ALS, underscoring the importance of treatments that can slow functional loss for those living with this fatal neurodegenerative condition," said Fumihiro Takahashi, Senior Biostatistician, Mitsubishi Tanabe Pharma Corporation and lead author of the publication. "This analysis provides additional data to help characterize functional outcomes and potential impact of RADICAVA ORS on disease progression in ALS." This analysis was funded and conducted by MTPA. The full publication is titled, "Analysis of Long-term Function and Survival of Edaravone Oral Suspension-Treated Patients With Amyotrophic Lateral Sclerosis Using PRO-ACT Data as Historical Placebo Controls." About the PRO-ACT Database PRO-ACT Dataset is the world's largest ALS clinical trial data repository, compiling placebo and treatment-arm data from 36 phase II/III clinical trials and over 12,500 fully anonymized longitudinal Subject records funded by The ALS Therapy Alliance, Prize4Life, Inc., Northeast ALS Consortium (NEALS), Neurological Clinical Research Institute of Mass. General Hospital, ALS Finding A Cure, and The ALS Association. Neurological Clinical Research Institute of Mass. General Hospital created and maintained the PRO-ACT Dataset and serves as the coordinating center and data distributor of the PRO-ACT Dataset. Find out more at . About Studies MT-1186-A01/A02/A03/A04 Study MT-1186-A01 (NCT04165824) was a phase 3, global, multicenter, open-label study that evaluated the long-term safety and tolerability of the approved edaravone oral suspension 105 mg On/Off dosing regimen over 48 weeks, and Study MT-1186-A03 (NCT04577404) was its extension study, which provided up to 96 weeks of additional treatment. Study MT-1186-A02 (NCT04569084), a post-marketing commitment following the FDA approval of RADICAVA® (edaravone), was a phase 3b, multicenter, double-blind, parallel-group, randomized study that evaluated whether investigational Once Daily edaravone oral suspension dosing was superior to the approved On/Off dosing based on Combined Assessment of Function and Survival, and assessed safety and tolerability over 48 weeks in patients with ALS; and Study MT-1186-A04 (NCT05151471) was its extension study, which provided up to 48 weeks of additional treatment. In Study MT-1186-A02, a pre-planned futility analysis was conducted after 50% of the planned study population (N=190) reached 48 weeks, which assessed the study's primary endpoint and the probability of the study results changing if all participants completed the 48-week study period. Through that interim analysis, the Independent Data Monitoring Committee (IDMC) concluded that there was a low statistical probability for the investigational once-daily dosing regimen to show superiority to the current on/off dosing regimen as measured by the ALS Functional Rating Scale Revised (ALSFRS-R) score at study completion; therefore, study discontinuation was recommended by the IDMC. About RADICAVA ORS® (edaravone) The U.S. Food and Drug Administration (FDA) approved RADICAVA ORS® (edaravone) on May 12, 2022, for the treatment of amyotrophic lateral sclerosis (ALS). In 2024, the FDA granted RADICAVA ORS Orphan Drug Exclusivity based on its major contribution to patient care by providing an oral suspension route of administration that avoids the burdens of IV administration. RADICAVA ORS is taken daily for 14 consecutive days followed by a 14-day drug-free period for the initial treatment cycle. For subsequent treatment cycles, RADICAVA ORS is taken for 10 days within a 14-day period followed by a 14-day drug-free period. Each 105 mg (5mL) dose of RADICAVA ORS should be taken in the morning after overnight fasting. Patients should not eat or drink (except water) within one hour after taking RADICAVA ORS.1 Edaravone was discovered and developed for ALS by Mitsubishi Tanabe Pharma Corporation (MTPC) and commercialized in the U.S. by Mitsubishi Tanabe Pharma America, Inc. (MTPA). The MTPC group companies began researching ALS in 2001 through an iterative clinical platform over a 13-year period. In 2015, edaravone was approved as RADICUT® for the treatment of ALS in Japan and South Korea. Marketing authorizations were subsequently granted in Canada (October 2018), Switzerland (January 2019), Indonesia (July 2020), Thailand (April 2021), Malaysia (December 2021), Australia (February 2023) and Brazil (February 2024). Marketing authorization for RADICAVA® Oral Suspension was granted in Canada (November 2022) and Switzerland (May 2023), and RADICUT® Oral Suspension 2.1% was granted regulatory approval in Japan in December 2022. To date, in the U.S., RADICAVA ORS, along with the previously available IV RADICAVA® (edaravone), have been used to treat over 19,000 people with ALS, with over 2.5-million days of therapy, and have been prescribed by over 2,600 HCPs.2-4 INDICATION RADICAVA ORS® (edaravone) is indicated for the treatment of amyotrophic lateral sclerosis (ALS). IMPORTANT SAFETY INFORMATION Hypersensitivity Reactions RADICAVA ORS® (edaravone) is contraindicated in patients with a history of hypersensitivity to edaravone or any of the inactive ingredients of this product. Hypersensitivity reactions (redness, wheals, and erythema multiforme) and cases of anaphylaxis (urticaria, decreased blood pressure, and dyspnea) have occurred. Patients should be monitored carefully for hypersensitivity reactions. If hypersensitivity reactions occur, discontinue RADICAVA ORS, treat per standard of care, and monitor until the condition resolves. Sulfite Allergic Reactions RADICAVA ORS contain sodium bisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown but occurs more frequently in asthmatic people. Adverse Reactions The most common adverse reactions (≥10%) reported in RADICAVA® (edaravone)-treated patients and at least 2% more frequently than placebo were contusion (15% vs 9%), gait disturbance (13% vs 9%), and headache (10% vs 6%), respectively. In an open label study, fatigue was also observed in 7.6% of patients receiving RADICAVA ORS. Pregnancy Based on animal data, RADICAVA ORS may cause fetal harm. To report suspected adverse reactions or product complaints, contact Mitsubishi Tanabe Pharma America, Inc., at 1-888-292-0058. You may also report suspected adverse reactions to the FDA at 1-800-FDA-1088 or . Please see the full Prescribing Information, also available at . About Mitsubishi Tanabe Pharma America, Inc. Based in Jersey City, N.J., Mitsubishi Tanabe Pharma America, Inc. (MTPA) is a wholly-owned subsidiary of Mitsubishi Tanabe Pharma Corporation (MTPC). It was established by MTPC to develop and advance our pipeline as well as commercialize approved pharmaceutical products in North America. For more information, please visit or follow us on X (formerly Twitter), Facebook and LinkedIn. About Mitsubishi Tanabe Pharma Corporation Mitsubishi Tanabe Pharma Corporation (MTPC) is one of the oldest pharmaceutical companies in the world, founded in 1678. MTPC is headquartered in Doshomachi, Osaka, the birthplace of Japan's pharmaceutical industry. MTPC sets the MISSION of "Creating hope for all facing illness." To that end, MTPC is working on the disease areas of central nervous system, immuno-inflammation, diabetes and kidney, and cancer. MTPC is focusing on "precision medicine" to provide drugs with high treatment satisfaction and additionally working to develop "around the pill solutions" to address specific patient concerns based on therapeutic medicine, including prevention of diseases, pre-symptomatic disease care, prevention of aggravation and prognosis. For more information, go to . Media inquiries: [email protected] 1 RADICAVA and RADICAVA ORS Prescribing Information. Jersey City, NJ: Mitsubishi Tanabe Pharma America, Inc.; 2022 2 Data on file. Mitsubishi Tanabe Pharma America, Inc. 3 Data on file. Mitsubishi Tanabe Pharma America, Inc. 4 Data on file. Mitsubishi Tanabe Pharma America, Inc. 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机会难得，千万别错过！ 融资的机会来了！~ 多家知名VC公司寻找优质投资标的， 感兴趣的管线包括： （1）针对实体瘤的创新性TCE、（2）新靶点/新核素的创新性核药、（3）Abeta双靶点等CNS创新药、（4）新靶点/新MOA的自免创新药。 请有相关产品的biotech公司立即联系药时代BD团队（BD@drugtimes.cn）！ 近日的Biohaven，喜忧参半。 2025年4月，Biohaven宣布获得6亿美元投资，用于加速开发和商业化troriluzole，这是喜事。 2025年5月，FDA宣布推迟troriluzole用于治疗脊髓小脑共济失调（SCA）的审批决定，原因为要对Biohaven近日提交的补充信息进行全面审查。受此消息影响，Biohaven股价当日暴跌19.53%，这是忧事。 2025年8月，Biohaven公布了2025年第二季度财报，决定终止troriluzole在强迫症领域的开发，这是雪上加霜。 命途多舛的troriluzole troriluzole是一款谷氨酸盐调节剂，属于riluzole（利鲁唑）第三代三肽前药。该药可以通过血浆中的氨肽酶转化为利鲁唑，从而降低突触中的谷氨酸水平，达到神经保护的作用。 利鲁唑则是一款神经保护剂，1995年被FDA批准用于ALS（渐冻症）的治疗。由于此药口服吸收差（生物利用度仅60%）、需要空腹服用、大剂量会导致肝损等不良特性，限制它在临床的广泛运用。 troriluzole作为利鲁唑的加强版，有着更好的生物利用度与更低的肝脏负担，且不受食物影响，依从性更高。 troriluzole的研发历程颇为坎坷。早在2016年，Biohaven就开始了troriluzole在脊髓小脑共济失调（SCA）领域的研发，但是结果不及安慰剂。 后经Biohaven回溯发现，本次研究的主要终点（一个8分的SARA量表）评分存在不一致性和偏差，影响了最终结果。 于是乎，Biohaven与FDA重新设计了一个新的主要终点，一个16分的评分量表（f-SARA）。换上f-SARA之后，troriluzole的命运并未因此改变，再一次败给了安慰剂。 因此，Biohaven退而求其次，将目光投向了细分的疾病基因型SCA3，并自己开发了一个新的复合量表，称为SCACOMS，结果在提交NDA后仍被FDA拒绝，理由很简单：关键3期临床试验未达到主要终点，所以不予开展实质性审查。 时间来到今年3月，Biohaven宣布troriluzole的欧洲上市之旅失败，撤回该药在EMA（欧洲药品管理局）的上市申请，该决定是在EMA对提交的数据进行评估并提出问题后做出的。 那么，EMA的判断是否会影响到更为严格的FDA？Biohaven在2024年全年报中宣布，troriluzole治疗全基因型SCA的NDA获得了FDA的受理与优先审批，预计PDUFA日期为2025年第三季度。 可惜的是，今年5月份，Biohaven宣布PDUFA日期推迟三个月至今年年底，并将计划召开咨询委员会会议 (AdCom)。 直至今日，troriluzole终止强迫症适应症开发后，该药便仅剩SCA这一个适应症，艰难地等待上市批准。 troriluzole屡战屡败的背后 从二级市场的反应来看，troriluzole终止强迫症适应症一事，并未掀起波澜，人们更为关注其SCA适应症的获批。 SCA是一大类罕见的常染色体显性遗传的神经退行性疾病，患病率约为8/10万~12/10万。目前全球尚无有效治疗SCA的药物，存在巨大的未满足临床需求。 这意味，troriluzole一旦获批，将成为全球首个FDA批准的SCA治疗药物。  于是乎，troriluzole在“罕见病”、“FIC”、“快速通道”、“优先审评”各类光环加持下，总给人一种“上市只是临门一脚”的错觉。 而troriluzole的屡战屡败，也成为了当下罕见病药物的上市缩影，特别是CNS领域新药研发与审评的复杂图景。 实打实的临床数据才是金标准，“巨大未被满足的临床需求”不能成为免死金牌，明知不可为而为之没有意义，不如多花些心思，在临床试验设计和结果分析阶段，积极与监管部门沟通和合作；在临床试验失败后去寻找适当的亚群体……只差一步到罗马，终究是未到罗马。 图片来源：即梦AI 一款具有良好稳定性、用于天疱疮的小分子环状多肽| 药时代BD项目 2025-08-13 1.5亿美元！Insmed拿下全球首款DPP1抑制剂 2025-08-13 一款具有减重增肌潜力的选择性小分子环状多肽MC4R激动剂 | 药时代BD项目 2025-08-12 版权声明/免责声明 本文为原创文章。 本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。 文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。 如有任何问题，请与我们联系。 衷心感谢! 药时代官方网站:www.drugtimes.cn 联系方式: 电话:13651980212 微信:27674131 邮箱:contact@drugtimes.cn 点击这里，查看更多精彩！