XERMELO(telotristat ethyl)250毫克是第一个也是唯一获FDA批准的口服治疗类癌综合征腹泻癌症患者转移性神经内分泌肿瘤
2017年2月28日,美国食品和药品监管局批准Xermelo(telotristat_ethyl)片与生长激素抑制素[somatostatin]类似物(SSA)治疗联用对单独SSA治疗没有充分控制成年有类癌综合征腹泻的治疗。
类癌综合证是一种症状的群集有时见于有类癌肿瘤人们。这些肿瘤是罕见，和往往缓慢生长。大多数类癌肿瘤是发现在胃肠道。类癌综合证发生在低于10 %有类癌肿瘤患者，通常地在肿瘤已播散至肝脏后。这些患者中肿瘤释放过量的激素 5-羟色胺，导致腹泻，不能控制腹泻的合并症包括体重减轻，营养不良，脱水，和电解质不平衡。
FDA的药品评价和研究中心内药物评价III办公室主任Julie Beitz，M.D.说：“今天的批准将提供用另外治疗选择不能适当类癌综合征腹泻患者，”。
Xermelo，在一个有SSA治疗方案，是被批准以片剂每天与食物口服三次。Xermelo抑制5-羟色胺生成通过类癌肿瘤和减低类癌综合征腹泻频数。
在一项12-周，双盲，安慰剂-对照试验在90有分化良好转移神经内分泌肿瘤和类癌综合征腹泻成年参加者确定Xermelo的安全性和疗效。这些患者是有四至12间每天肠运动尽管在一个稳定剂量使用SSA共至少三个月。参加者保留用他们的SSA治疗，和被随机化至加安慰剂或用Xermelo治疗每天三次。接受Xermelo加至他们的SSA治疗患者经受一个在平均肠运动频数比用SSA和安慰剂患者更大的减低。特别是，33 %参加者随机化至Xermelo加至至SSA经受一个平均减低两次肠运动每天，与之比较，随机化至添加安慰剂至SSA患者的4 %。
Xermelo的最常见副作用包括恶心，头痛，肝酶γ-谷酰基转移酶的增加水平，抑郁，液体的积蓄致肿胀(周围水肿)，胀气，食欲减退和发热。Xermelo可能致便秘，而在患者他的肠运动频数是低于四次肠运动每天发展便秘的风险可能被增加。在临床试验中用一个比推荐剂量Xermelo较高治疗的患者发生严重便秘。一例患者需要住院和两例其他患者发生合并症或小肠穿孔或小肠梗阻。对严重便秘患者应被监视。如一位患者经受严重便秘或严重，持续或恶化的腹痛，他们应终止Xermelo和联系他们的卫生保健提供者。
FDA授权这个申请快速通道指定和优先审评。这个药物还接受孤儿药物指定，它提供奖励帮助和鼓励对罕见疾病药物的开发。
Xermelo被制造Woodlands，总部在德克萨斯州Lexicon Pharmaceuticals，Inc.
FDA Approves Lexicon Drug XERMELO™ (telotristat ethyl) 250 mg As First And Only Oral Treatment For Carcinoid Syndrome Diarrhea In Cancer Patients With Metastatic Neuroendocrine Tumors
U.S. Food and Drug Administration (FDA) has approved XERMELO™ (telotristat ethyl) 250 mg as a first and only orally administered therapy for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy[i]. Carcinoid syndrome is a rare and debilitating condition that affects people with metastatic neuroendocrine tumors (mNETs)[ii]. XERMELO targets the overproduction of serotonin inside mNET cells[iii], providing a new treatment option for patients suffering from carcinoid syndrome diarrhea. This new treatment is now available by prescription and will be in select specialty pharmacies beginning March 6, 2017.
"Today's approval of XERMELO represents a shift in the treatment paradigm of carcinoid syndrome diarrhea for cancer patients who are inadequately controlled by SSA therapy, and until now, have had limited options to manage this debilitating condition," said Lonnel Coats, Lexicon's president and chief executive officer. "We are proud to have discovered and developed this ground-breaking orphan drug, and it is an honor to make it available for the thousands of patients currently suffering from this condition who wish to lead a more routine life with fewer incidences of severe diarrhea."
Carcinoid syndrome is a rare condition that occurs in patients living with mNETs[iv] and is characterized by frequent and debilitating diarrhea that often prevents patients from leading active, predictable lives, as well as by facial flushing, abdominal pain, fatigue and, over time, heart valve damage.
"The approval of XERMELO establishes a new treatment option for patients with carcinoid syndrome diarrhea that is inadequately controlled by SSA therapy," said Matthew H. Kulke, M.D., TELESTAR primary investigator, director of the Program in Neuroendocrine and Carcinoid Tumors at Dana Farber Cancer Institute and Professor of Medicine, Harvard Medical School. "Inhibition of tumoral serotonin production represents a novel approach for patients with this condition. Studies have shown that XERMELO can reduce the debilitating effects of carcinoid syndrome diarrhea and has a favorable efficacy and safety profile in patients who currently have limited treatment options."
About XERMELO™
Discovered using Lexicon's unique approach to gene science, XERMELO is the first and only approved oral therapy for carcinoid syndrome diarrhea. XERMELO targets tryptophan hydroxylase, an enzyme that mediates the excess serotonin production within mNET cells.
Lexicon has built the in-house capability and infrastructure to launch and market XERMELO in the U.S., where it retains all commercialization rights. Lexicon also retains rights to market telotristat ethyl in Japan. Lexicon has established a license and collaboration agreement with Ipsen to commercialize telotristat ethyl in Europe and other countries outside of U.S. and Japan. For more information about XERMELO, please visit www.xermelo.com.
XERMELO™ Important Safety Information
•Warnings and Precautions: XERMELO may cause constipation which can be serious. Monitor for signs and symptoms of constipation and/or severe, persistent, or worsening abdominal pain in patients taking XERMELO. Discontinue XERMELO if severe constipation or severe persistent or worsening abdominal pain develops.
•Adverse Reactions: The most common adverse reactions (≥5%) include nausea, headache, increased GGT, depression, peripheral edema, flatulence, decreased appetite, and pyrexia.
•Drug Interactions: If necessary, consider increasing the dose of concomitant CYP3A4 substrates, as XERMELO may decrease their systemic exposure.
http://www.xermelo.com/Media/Default/pdfs/Product_Info_telotristat_etiprate.pdf |
