Givinostat Hydrochloride

近日，Capricor Therapeutics宣布，将于10月向美国FDA提交其在研细胞疗法Deramiocel（CAP-1002）的生物制品许可申请（BLA），用于治疗杜氏肌营养不良症（DMD）相关的心肌病。 根据报道，DMD心肌病是DMD患者的主要死亡原因，目前还没有批准的DMD心肌病药物。 通过外泌体介导治疗 CAP-1002是一种基于外泌体作用的异体细胞治疗，由心球衍生细胞 （CDC） 组成，CDC是一种源自于健康人类心脏细胞的内源性基质细胞群。 CAP-1002通过分泌外泌体来进行免疫调节、抗炎和抗纤维化，以减缓DMD疾病进展。同时，CAP-1002的外泌体中包含有microRNA等活性物质，通过这类非编码RNA，能够改变巨噬细胞和其他靶细胞的基因表达，从而抑制DMD中的全身炎症，以及刺激组织再生长。 另外，相较于其他种类的细胞与基因治疗，CAP-1002不是一次性治疗药物，而是一种需要周期性给药的细胞药物。根据Capricor公司的研究显示，患者每3个月给药一次CAP-1002，每次剂量为1.5亿个细胞。 目前，CAP-1002已经获得了来自FDA授予的再生医学先进疗法（RMAT）和孤儿药指定，用于治疗杜氏肌营养不良症（DMD）。 3年临床数据 根据报道，CAP-1002的BLA申请将基于2期研究HOPE-2、HOPE-2开放标签扩展（HOPE-2 OLE）的数据；并与范德堡大学医学中心和辛辛那提儿童医院医学中心提供的自然历史数据进行比较。 在6月早些时候，Capricor公司披露了HOPE-2 OLE的3年疗效结果，结果显示：与DMD外部数据集（由辛辛那提儿童医院医学中心(CCHMC)提供）相比，接受CAP-1002的患者在治疗3年后继续显示出积极的益处。此外，在整个研究过程中，HOPE-2-OLE研究期间CAP-1002继续表现始终如一的良好耐受安全性。 来自HOPE-2 OLE研究的数据显示，多种心脏测量都有所改善，包括包括左心室射血分数 （LVEF） 以及左心室收缩末期容积 （LVESV） 和左心室舒张末期容积 （LVEDV）。此外，在HOPE-2随机试验开始时，在射血分数较高（> 45%） 的患者中观察到心脏功能更好的改善。 2022年3月，《柳叶刀》刊登了CAP-1002的HOPE-2研究数据。 2018年3月1日至2020年3月31日期间，26名DMD男性患者被纳入试验。其中，8名患者被随机分配到CAP-1002组，12名患者被分配到安慰剂组，6名患者因筛查失败而未被随机分配。一名随机分配到CAP-1002的患者在第3个月（第二次输注）因严重过敏反应推出。三名随机分配到安慰剂组的患者选择停药。最后安慰剂组有10名参与者，CAP-1002组有8名参与者。 结果显示：与基线相比，PUL 1.2评分的平均12个月变化，CAP-1002优于安慰剂，输注CAP-1002可以减缓71%的功能丧失。中期PUL 1.2的6个月变化的次要终点在各组之间存在显著差异，CAP-1002优于安慰剂。 延伸阅读：《柳叶刀》：细胞治疗能够显著延缓DMD的疾病进展 此外，为了支持CAP-1002在DMD骨骼肌肌病的潜在扩展标签，Capricor公司计划将3期研究HOPE-3中的队列A和B合并作为批准后研究，目前不打算对队列A进行揭盲，预计将于2024年第四季度进行。 小结 值得注意的是，Capricor公司正在为支持BLA和潜在的商业化而建立内部GMP生产，包括正在扩大圣地亚哥的工厂。 目前，全球市场上，用于DMD治疗的药物有多种，包括外显子跳跃疗法（Exondys 51、Vyondys 53、Amondys 45、Viltepso）、小分子药物（Ataluren、Duvyzat）、激素治疗（泼尼松、泼尼松龙、地夫可特等）、以及重磅药物AAV基因治疗Elevidys。 但是，尚无针对DMD心肌病的药物获批上市。 参考资料： 1.https://www.capricor.com/investors/news-events/press-releases/detail/291/capricor-therapeutics-announces-intent-to-file-biologics 2.https://www.capricor.com/investors/news-events/press-releases/detail/284/capricor-therapeutics-announces-long-term-benefit-of 本周好文推荐 如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

PITTSBURGH, Pa., July 25, 2024 /PRNewswire/ -- PANTHERx® Rare, a leader in rare disease product patient access and support services in the United States, is pleased to announce it is partnering with ITF Therapeutics LLC for the U.S. distribution of DUVYZAT™ (givinostat), the first nonsteroidal drug approved to treat patients with all genetic variants of Duchenne muscular dystrophy (DMD) aged six years and older. DUVYZAT, a twice daily oral suspension, is a histone deacetylase (HDAC) inhibitor that reduces inflammation and loss of muscle observed in DMD. DMD is a rare and serious muscle disorder affecting approximately 1 in 5,000 male births worldwide and is caused by a variant in the DMD gene located on the X chromosome. This gene is responsible for regulating the production of dystrophin, which is a protein located in skeletal and cardiac muscle cells. Disease onset in DMD is typically observed between three and five years of age and progression is characterized by muscle wasting and weakness in the voluntary muscles of the body. The disease typically affects muscles closest to the trunk (e.g., upper legs, upper arms, shoulders, and pelvic muscles) first and then progresses outward toward the extremities. By late teenage years, many patients develop additional potentially life-threatening complications including cardiomyopathy and respiratory failure. "We are looking forward to serving the needs of people living with Duchenne muscular dystrophy and their families and caregivers by streamlining the process associated with getting rare medications from the people who create them to the people who need them most. We appreciate ITF Therapeutics' commitment to making a difference in the lives of patients with this disease," said Rob Snyder, CEO of PANTHERx® Rare Pharmacy. About PANTHERx Rare PANTHERx Rare is a dual-accredited specialty pharmacy focused on rare and orphan disease, distributing several orphan products and providing access and support services to those needing them most. PANTHERx transforms lives by delivering medicine breakthroughs, clinical excellence, and access solutions to people living with rare and devastating conditions. While each rare condition affects few people, together all rare diseases impact an estimated 25 to 30 million Americans. Currently over 7,000 rare diseases have been identified and more than 90% of rare diseases are still without an FDA-approved treatment. Changes in federal policy and advances in science have led to a surge in FDA orphan drug approvals, providing tremendous hope to the rare disease community. PANTHERx is a dual-accredited specialty pharmacy, holding distinctions in rare disease including the Accreditation Commission for Health Care (ACHC) Distinction in Orphan Drugs and Utilization Review Accreditation Commission (URAC) Rare Disease Center of Excellence. As a pharmacy focused on patient satisfaction, PANTHERx is now a six-time winner of the prestigious MMIT Patient Choice Award, including the 2023 honor. PANTHERx is headquartered in Pittsburgh, Pennsylvania and is licensed in all 50 states and US territories. About DUVYZAT™ (givinostat) DUVYZAT is a U.S. FDA approved therapy indicated for the treatment of patients six years of age and older with Duchenne muscular dystrophy (DMD) that was discovered through the research and development efforts of Italfarmaco in collaboration with Telethon and Duchenne Parent Project (Italy). DUVYZAT is a histone deacetylase (HDAC) inhibitor that modulates the deregulated activity of HDACs in the dystrophic muscle, which is a major consequence of the lack of dystrophin associated with DMD. Though the exact mechanism of action of DUVYZAT is unknown, it is believed to inhibit HDAC pathological overactivity to address the cascade of events leading to muscle damage, thereby counteracting the disease pathology and slowing down muscle deterioration. References: Duvyzat. Package Insert. ITF Therapeutics, LLC; 2024. FDA Approves Nonsteroidal Treatment for Duchenne Muscular Dystrophy. FDA; March 21, 2024; Duchenne Muscular Dystrophy. NORD; (accessed April 2, 2024) For more information, please contact [email protected] SOURCE PANTHERx Rare Pharmacy