今天，美国食品和药物管理局批准Turalio（pexidartinib）胶囊用于治疗患有症状性腱鞘巨细胞瘤（TGCT）的成年患者，这些患者与严重的发病率或功能限制相关并且对手术的改善没有反应。

“TGCT可引起患者的衰弱症状，如疼痛，僵硬和运动受限。肿瘤可显着影响患者的生活质量并导致严重残疾，“FDA药物评估与研究中心FDA肿瘤学中心主任，血液学和肿瘤学产品代理主任Richard Pazdur医学博士说。 。 “手术是主要的治疗选择，但有些患者不符合手术条件，即使手术后肿瘤也会复发。今天的批准是FDA批准的第一种治疗这种罕见疾病的疗法。“

TGCT是一种罕见的肿瘤，影响滑膜（覆盖关节间隙表面的薄层组织）和腱鞘（覆盖肌腱的膜层，肌腱是连接肌肉与骨骼的纤维组织）。肿瘤很少是恶性的，但导致滑膜和腱鞘变厚和过度生长，对周围组织造成损害。

Turalio的批准是基于120名患者的多中心国际临床试验结果，其中59名患者接受了安慰剂治疗。主要疗效终点是治疗25周后分析的总反应率（ORR）。临床试验显示接受Turalio患者的ORR有统计学意义上的显着改善，ORR为38％，而接受安慰剂的患者无ORR。完全反应率为15％，部分反应率为23％。在最初的反应之后，至少有6个月被跟踪的23名反应者中，有22名维持了6个月或更长时间的反应，并且13名反应者中有13名被追踪至少12个月在初始响应之后，他们的响应持续了12个月或更长时间。

Turalio的处方信息包括盒装警告，为医疗保健专业人员和患者提供有关严重和可能致命的肝损伤风险的建议。医疗保健专业人员应在开始治疗前和治疗期间的特定时间间隔监测肝脏检查。如果肝脏检查异常，根据肝脏损伤的严重程度，可能需要停用Turalio，减少剂量或永久停药。 Turalio仅通过Turalio风险评估和缓解策略（REMS）计划提供。

服用Turalio的患者常见的副作用是乳酸脱氢酶增加（有助于在体内产生能量的蛋白质），天冬氨酸氨基转移酶增加（主要在肝脏中但在肌肉中的酶），头发颜色丧失，丙氨酸氨基转移酶增加（酶主要在肝脏和肾脏）和胆固醇增加。其他副作用包括中性粒细胞减少症（白细胞水平低，有助于免疫系统抵御疾病和感染），碱性磷酸酶增加（主要存在于骨骼和肝脏细胞中的酶），淋巴细胞减少（白细胞有帮助）免疫系统防御疾病和感染），眼睛水肿（眼睛周围肿胀），血红蛋白减少（携带氧气的红细胞中的蛋白质），皮疹，味觉障碍（味觉改变）和磷酸盐减少（电解质有助于能量） ）。

美国食品和药物管理局建议医疗保健专业人员告知生育年龄的女性和男性与生殖潜力的女性伴侣在Turalio治疗期间使用有效的避孕措施。孕妇或哺乳期妇女不应服用Turalio，因为它可能对正在发育的胎儿或新生儿造成伤害。 Turalio必须免除患者用药指南，该指南描述了有关药物用途和风险的重要信息。

FDA批准了此应用程序突破性治疗指定和优先审查指定。 Turalio还获得了Orphan药物的称号，该药物提供奖励以协助和鼓励开发用于罕见疾病的药物。 FDA批准Turalio批准Daiichi Sankyo。

资料来源：FDA

发布时间：2019年8月

Company: Daiichi Sankyo
Date of Approval: August 2, 2019
Treatment for: Tenosynovial Giant Cell Tumor

Turalio (pexidartinib) is a kinase inhibitor indicated for the treatment of symptomatic tenosynovial giant cell tumor (TGCT) in adults.

Today, the U.S. Food and Drug Administration granted approval to Turalio (pexidartinib) capsules for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not responsive to improvement with surgery.

“TGCT can cause debilitating symptoms for patients such as pain, stiffness and limitation of movement. The tumor can significantly affect a patient’s quality of life and cause severe disability,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Surgery is the primary treatment option, but some patients are not eligible for surgery, and tumors can recur, even after the procedure. Today’s approval is the first FDA-approved therapy to treat this rare disease.”

TGCT is a rare tumor that affects the synovium (thin layer of tissue that covers the surfaces of the joint spaces) and tendon sheaths (layer of membrane that covers tendons, which are fibrous tissue that connect muscle to bone). The tumor is rarely malignant but causes the synovium and tendon sheaths to thicken and overgrow, causing damage to surrounding tissue.

The approval of Turalio was based on the results of a multi-center international clinical trial of 120 patients, 59 of whom received placebo. The primary efficacy endpoint was the overall response rate (ORR) analyzed after 25 weeks of treatment. The clinical trial demonstrated a statistically significant improvement in ORR in patients who received Turalio, with an ORR of 38%, compared to no responses in patients who received placebo. The complete response rate was 15% and the partial response rate was 23%. A total of 22 out of 23 responders who had been followed for a minimum of six months following the initial response maintained their response for six or more months, and a total of 13 out of 13 responders who had been followed for a minimum of 12 months following the initial response maintained their response for 12 or more months.

The prescribing information for Turalio includes a Boxed Warning to advise health care professionals and patients about the risk of serious and potentially fatal liver injury. Health care professionals should monitor liver tests prior to beginning treatment and at specified intervals during treatment. If liver tests become abnormal, Turalio may need to be withheld, the dose reduced, or permanently discontinued, depending on the severity of the liver injury. Turalio is available only through the Turalio Risk Evaluation and Mitigation Strategy (REMS) Program.

Common side effects for patients taking Turalio were increased lactate dehydrogenase (proteins that helps produce energy in the body), increased aspartate aminotransferase (enzymes that are mostly in the liver but also in muscles), loss of hair color, increased alanine aminotransferase (enzymes that are primarily in the liver and kidney) and increased cholesterol. Additional side effects included neutropenia (low level of white blood cells that help the immune system defend against disease and infection), increased alkaline phosphatase (enzymes that are mostly in the cells of bone and the liver), decreased lymphocytes (white blood cells that help the immune system defend against disease and infection), eye edema (swelling around the eyes), decreased hemoglobin (protein in red blood cells that carry oxygen), rash, dysgeusia (altered sense of taste) and decreased phosphate (electrolytes that help with energy).

The FDA advises health care professionals to tell females of reproductive age and males with a female partner of reproductive potential to use effective contraception during treatment with Turalio. Women who are pregnant or breastfeeding should not take Turalio because it may cause harm to a developing fetus or newborn baby. Turalio must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks.

The FDA granted this application Breakthrough Therapy designation and Priority Reviewdesignation. Turalio also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted the approval of Turalio to Daiichi Sankyo.

Source: FDA

Posted: August 2019