2014年4月15日美国食品药品监督管理局(FDA)批准Tanzeum(albiglutide)皮下注射，与饮食和锻炼一起，有2型糖尿病成年中改善血糖控制。
Tanzeum是一种胰高血糖素样肽-1(GLP-1)受体激动剂，一种激素有助于血糖水平正常化。在8项临床试验涉及2,000以上有2型糖尿病患者中评价药物的安全性和有效性。参加该试验患者显示其HbA1c水平改善(血红蛋白A1c或糖基化血红蛋白，血糖控制的一种测量)。
Tanzeum曾被作为单药治疗和与2型糖尿病其他治疗联合，包括二甲双胍[metformin]，格列美脲[glimepiride]，吡格列酮[pioglitazone]，和胰岛素。Tanzeum不应被用于治疗1型糖尿病人们；在其血或尿有酮体增高的患者(糖尿病酮症酸中毒)；或对不能用饮食和运动处理的患者作为一线治疗。
Tanzeum有一个黑框警告警告在啮齿类研究中有些GLP-1受体激动剂曾观察到甲状腺肿瘤(甲状腺C-细胞肿瘤)，但不知道 Tanzeum是否引起甲状腺C-细胞肿瘤，包括在人中一种类型甲状腺癌被称为甲状腺髓样癌(MTC)，Tanzeum不应在有个人或家族MTC史或有2型多发性内分泌腺瘤综合征(一种疾病患者机体中有一种以上腺体肿瘤和他们容易患MTC)患者中使用。
FDA 正在要求对Tanzeum进行以下上市后研究：
⑴一项临床试验评价在儿童患者中给药，疗效，和安全性；
⑵一项甲状腺髓样癌(MTC)病例注册至少15年时间以确定与Tanzeum相关MTC发生率的任何增加；
⑶一项心血管结局试验(CVOT)在有高基线心血管疾病风险患者中评价Tanzeum的心血管风险。
在临床试验中，用Tanzeum治疗患者最常见观察到的副作用是腹泻，恶心，和注射部位反应。
FDA批准Tanzeum有一个风险评估和减灾战略(REMS)，由交流计划告知卫生保健提供者伴Tanzeum严重风险组成。
Tanzeum，特拉华州威尔明顿GlaxoSmithKline L.L.C.制造。
Tanzeum (albiglutide)
Company: GlaxoSmithKline
Approval Status: Approved April 2014
Treatment Area: type II diabetes mellitus
Tanzeum General Information
Tanzeum (albiglutide) is an agonist of the albumin-based glucagon-like peptide (GLP)-1 fusion protein. It augments glucose-dependent insulin secretion and slows gastric emptying.
Tanzeum is specifically indicated as an adjunct to diet and exercise to improve glycemic control in adults with type II diabetes mellitus.
Tanzeum is supplied as a solution for subcutaneous injection. The recommended dose is 30 mg once weekly given as a subcutaneous injection in the abdomen, thigh, or upper arm region. The dosage may be increased to 50 mg once weekly if the glycemic response is inadequate. Tanzeum may be administered at any time of day without regard to meals. It should be administered once a week on the same day each week. The day of weekly administration may be changed if necessary as long as the last dose was administered 4 or more days before. If a dose is missed, Tanzeum should be administered as soon as possible within 3 days after the missed dose. Thereafter, dosing can resume on the usual day of administration. If it is more than 3 days after the missed dose, dosing should wait until the next regularly scheduled weekly dose.
Tanzeum Clinical Results
FDA Approval
The FDA approval of Tanzeum was based on a 52-week, randomized, double-blind, placebo-controlled, multicenter trial. A total of 296 subjects with type 2II diabetes inadequately controlled on diet and exercise were randomized Tanzeum 30 mg SC once weekly, Tanzeum 30 mg SC once weekly uptitrated to 50 mg once weekly at Week 12, or placebo. Compared with placebo, treatment with Tanzeum 30 mg or 50 mg resulted in statistically significant reductions in HbA1c from baseline at Week 52. The adjusted mean change in weight from baseline did not differ significantly between Tanzeum (-0.4 to -0.9 kg) and placebo (-0.7 kg) at Week 52.
Tanzeum Side Effects
Adverse effects associated with the use of Tanzeum may include, but are not limited to, the following:
•upper respiratory tract infection
•diarrhea
•nausea
•injection site reaction
Tanzeum Mechanism of Action
Tanzeum (albiglutide) is a GLP-1 receptor agonist, a recombinant fusion protein comprised of 2 tandem copies of modified human GLP-1 genetically fused in tandem to human albumin. The human GLP-1 fragment sequence 7 36 has been modified with a glycine substituted for the naturally-occurring alanine at position 8 in order to confer resistance to dipeptidylpeptidase IV (DPP-IV) mediated proteolysis. The human albumin moiety of the recombinant fusion protein, together with the DPP-IV resistance, extends the half-life allowing once-weekly dosing.
Tanzeum Additional Information
For additional information regarding Tanzeum or type II diabetes, please visit the Tanzeum web page.
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TANZEUM Rx
Generic Name and Formulations:
Albiglutide [recombinant fusion protein] 30mg, 50mg; per Pen; lyophilized pwd for SC inj after reconstitution; preservative-free.
Company:
GlaxoSmithKline Pharmaceuticals
Indications for TANZEUM:
Adjunct to diet and exercise, to improve glycemic control in adults with type 2 diabetes. Limitations of use: not recommended as first-line treatment for patients inadequately controlled on diet and exercise. Not studied in combination with prandial insulin or with history of pancreatitis. Not for treating type 1 diabetes or diabetic ketoacidosis. Not a substitute for insulin. Not recommended in patients with pre-existing severe GI disease.
Adult Dose for TANZEUM:
Give by SC inj in the abdomen, thigh, or upper arm on the same day each week without regard to meals. Initiate at 30mg once weekly; may increase to 50mg once weekly if inadequate response. Renal impairment: caution with initiating or escalating doses.
Children's Dose for TANZEUM:
<18yrs: not established.
Pharmacological Class:
Glucagon-like peptide-1 (GLP-1) receptor agonist.
Contraindications:
History (personal or family) of medullary thyroid carcinoma. Multiple endocrine neoplasia syndrome type 2.
Warnings/Precautions:
Inform patients of thyroid cancer risk and symptoms. Monitor for pancreatitis; discontinue if suspected; do not restart if confirmed. History of pancreatitis; consider other antidiabetic therapies. Monitor renal function in renally-impaired patients reporting severe GI reactions. Pregnancy (Cat.C). Nursing mothers: not recommended.
Interactions:
Increased risk of hypoglycemia with concomitant sulfonylureas or insulin; consider reducing their doses. May affect absorption of other oral drugs (delayed gastric emptying).
Adverse Reactions:
Upper respiratory tract infection, diarrhea, nausea, inj site reaction; acute pancreatitis, hypersensitivity reactions (discontinue if occurs).
How Supplied:
Single-dose Pen—4
近日，美国FDA批准阿必鲁泰(Albiglutide；商品名Tanzeum)皮下注射剂结合饮食与运动用于改善2型糖尿病成人患者的血糖控制。在美国，大约有2400万人受2型糖尿病影响，占美国确诊糖尿病病例的90%以上。随着时间的推移，高血糖水平会增加严重并发症风险，包括心脏病、失明及神经和肾脏损害。
“对美国成千上万的2型糖尿病患者来说，阿必鲁泰是一种新的治疗选择，”FDA药品评价与研究中心药物评价II办公室主任、医学博士、公共卫生学硕士Curtis Rosebraugh称。“这款药物可以单独使用，或在糖尿病整个管理中添加到现有治疗方案中控制血糖水平。”
阿必鲁泰是一种胰高血糖素样肽-1(GLP-1)受体激动剂，一种帮助血糖水平正常化的激素。这款药物的安全性及有效性通过8项由2000多名2型糖尿病患者参与的临床试验得到评价。参与试验患者的HbA1c水平显示有改善（糖化血红蛋白A1c或称糖基化血红蛋白，是一种血糖控制指标）。
阿必鲁泰已作为一款单独药物和与其它2型糖尿病药物合并用药进行了研究，包括二甲双胍、格列美脲、吡格列酮及胰岛素。阿必鲁泰不应用于治疗1型糖尿病患者，以及血液及尿中酮体升高（糖尿病酮症酸中毒）的患者，也不能作为一线治疗药物用于不能通过饮食及锻炼来管理的糖尿病患者。
阿必鲁泰带有一项黑框警告，警告在某些使用GLP-1受体激动剂的啮齿类动物研究中观察有甲状腺肿瘤，但不清楚阿必鲁泰是否会引起甲状腺C细胞瘤，包括出现在人身上的甲状腺髓样瘤(MTC)。阿必鲁泰不应用于个人或家庭有MTC病史的患者，不能用于2型多发性内分泌腺瘤综合征（一种患者体内一种以上腺体出现肿瘤的疾病，使患者倾向于发展成MTC）患者。
FDA要求对阿必鲁泰进行以下上市后研究：
一项在儿科患者身上评价给药剂量、有效性及安全性的临床试验；至少15年期的甲状腺髓样瘤登记，以确定甲状腺髓样瘤的发生率是否与阿必鲁泰有关联；一项心血管结局试验(CVOT)，评价阿必鲁泰在心血管疾病高基线风险患者身上的心血管风险。
在临床试验中，阿必鲁泰用药患者出现的最常见副作用有腹泻、恶心和注射部位反应。FDA批准阿必鲁泰附带一项风险评估和减轻战略（REMS），REMS含有一个沟通计划，以通知卫生保健提供商有关阿必鲁泰的严重风险。阿必鲁泰由位于特拉华州威尔明顿的葛兰素史克生产。
FDA NEWS RELEASE
For Immediate Release: April 15, 2014
Media Inquiries: Andrea Fischer, 301-796-0393, andrea.fischer@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA
FDA approves Tanzeum to treat type 2 diabetes
The U.S. Food and Drug Administration today approved Tanzeum (albiglutide) subcutaneous injection to improve glycemic control, along with diet and exercise, in adults with type 2 diabetes.
Type 2 diabetes affects approximately 24 million people and accounts for more than 90 percent of diabetes cases diagnosed in the United States. Over time, high blood sugar levels can increase the risk for serious complications, including heart disease, blindness, and nerve and kidney damage.
"Tanzeum is a new treatment option for the millions of Americans living with type 2 diabetes," said Curtis Rosebraugh, M.D., M.P.H., director of the Office of Drug eva luation II in the FDA’s Center for Drug eva luation and Research. “It can be used alone or added to existing treatment regimens to control blood sugar levels in the overall management of diabetes.”
Tanzeum is a glucagon-like peptide-1 (GLP-1) receptor agonist, a hormone that helps normalize blood sugar levels. The drug’s safety and effectiveness were eva luated in eight clinical trials involving more than 2,000 patients with type 2 diabetes. Patients participating in the trials showed an improvement in their HbA1c level (hemoglobin A1c or glycosylated hemoglobin, a measure of blood sugar control).
Tanzeum has been studied as a stand-alone therapy and in combination with other type 2 diabetes therapies, including metformin, glimepiride, pioglitazone, and insulin. Tanzeum should not be used to treat people with type 1 diabetes; those who have increased ketones in their blood or urine (diabetic ketoacidosis); or as first-line therapy for patients who can’t be managed with diet and exercise.
Tanzeum has a Boxed Warning to warn that tumors of the thyroid gland (thyroid C-cell tumors) have been observed in rodent studies with some GLP-1 receptor agonists, but that it is unknown whether Tanzeum causes thyroid C-cell tumors, including a type of thyroid cancer called medullary thyroid carcinoma (MTC), in humans. Tanzeum should not be used in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (a disease where patients have tumors in more than one gland in their body and that predisposes them to MTC).
The FDA is requiring the following post-marketing studies for Tanzeum:
•a clinical trial to eva luate dosing, efficacy, and safety in pediatric patients;
•a medullary thyroid carcinoma (MTC) case registry of at least 15 years duration to identify any increase in MTC incidence related to Tanzeum;
•a cardiovascular outcomes trial (CVOT) to eva luate the cardiovascular risk of Tanzeum in patients with high baseline risk of cardiovascular disease.
In clinical trials, the most common side effects observed in patients treated with Tanzeum were diarrhea, nausea, and injection site reactions.
The FDA approved Tanzeum with a Risk eva luation and Mitigation Strategy (REMS), which consists of a communication plan to inform health care providers about the serious risks associated with Tanzeum.
Tanzeum is manufactured by GlaxoSmithKline, L.L.C., Wilmington, Del.
Tanzeum (Albiglutide) Injection
Company: GlaxoSmithKline LLC
Application No.: 125431
Approval Date: 4/15/2014
Persons with disabilities having problems accessing the PDF files below may call (301) 796-3634 for assistance.
Pharmacological Class:
Glucagon-like peptide-1 (GLP-1) receptor agonist.
Active Ingredient(s):
Albiglutide [recombinant fusion protein] 30mg, 50mg; per Pen; lyophilized pwd for SC inj after reconstitution; preservative-free.
Company
GlaxoSmithKline Pharmaceuticals
Indication(s):
Adjunct to diet and exercise, to improve glycemic control in adults with type 2 diabetes. Limitations of use: not recommended as first-line treatment for patients inadequately controlled on diet and exercise. Not studied in combination with prandial insulin or with history of pancreatitis. Not for treating type 1 diabetes or diabetic ketoacidosis. Not a substitute for insulin. Not recommended in patients with pre-existing severe GI disease.
Pharmacology:
Tanzeum is an agonist of the GLP-1 receptor and augments glucose-dependent insulin secretion. GLP-1 also suppresses glucagon secretion during periods of hyperglycemia and slows gastric emptying.
Clinical Trials:
Tanzeum was studied as monotherapy and in combination with metformin, metformin + sulfonylurea, thiazolidinedione ± metformin, and insulin glargine ± oral antidiabetics. The efficacy of Tanzeum was compared with placebo, glimepiride, pioglitazone, liraglutide, sitagliptin, insulin lispro, and insulin glargine.
Tanzeum as monotherapy was eva luated in a 52-week, randomized, double-blind, placebo-controlled, multicenter trial in patients with type 2 diabetes (n=296). Patients were randomized to Tanzeum 30mg SC once weekly, Tanzeum 30mg SC once weekly uptitrated to 50mg once weekly at Week 12, or placebo.
The primary endpoint was the mean change in HbA1c from baseline to Week 52. Results showed that Tanzeum 30mg had a mean change in HbA1c of −0.7% (difference from placebo −0.8; [95% CI: −1.1, −0.6]) and Tanzeum 50mg had a mean change in HbA1c of −0.9% (difference from placebo −1.0; [95% CI: −1.3, −0.8]). Compared with placebo, treatment with Tanzeum 30mg and 50mg resulted in statistically significant reductions in HbA1c from baseline at Week 52 (P<0.0001).
The efficacy of Tanzeum was also eva luated as combination therapy in a 104-week randomized, double-blind, multicenter trial in patients with type 2 diabetes (n=999) inadequately controlled on background metformin therapy (≥1,500mg daily). Patients were randomized to Tanzeum 30mg once weekly with optional uptitration to 50mg after minimum of 4 weeks (n=297), placebo (n=100), sitagliptin 100mg daily (n=300), or glimepiride 2mg daily (n=302).
Results in this trial showed the change in HbA1c for Tanzeum was −0.6% (difference from placebo −0.9; [95% CI: −1.16, −0.65], sitagliptin −0.4; [95% CI: −0.53, −0.17], and glimepiride −0.3; [95% CI: −0.45, −0.09]). Compared with placebo, sitagliptin, and glimepiride, treatment with Tanzeum resulted in significantly greater reduction in HbA1c from baseline at Week 104 (P<0.0137).
For more clinical trial data, see full labeling.
Legal Classification:
Rx
Adults:
Give by SC inj in the abdomen, thigh, or upper arm on the same day each week without regard to meals. Initiate at 30mg once weekly; may increase to 50mg once weekly if inadequate response. Renal impairment: caution with initiating or escalating doses.
Children:
<18years: not established.
Contraindication(s):
History (personal or family) of medullary thyroid carcinoma. Multiple endocrine neoplasia syndrome type 2.
Warnings/Precautions:
Inform patients of thyroid cancer risk and symptoms. Monitor for pancreatitis; discontinue if suspected; do not restart if confirmed. History of pancreatitis; consider other antidiabetic therapies. Discontinue if hypersensitivity occurs. Monitor renal function in renally-impaired patients reporting severe GI reactions. Pregnancy (Category C). Nursing mothers: not recommended.
Interaction(s)
Increased risk of hypoglycemia with concomitant sulfonylureas or insulin; consider reducing their doses. May affect absorption of other oral drugs (delayed gastric emptying).
Adverse Reaction(s)
Upper respiratory tract infection, diarrhea, nausea, injection site reaction; acute pancreatitis.
How Supplied:
Single-dose Pen—4
LAST UPDATED:
8/29/2014
