罗氏终止试验性降糖药阿格列扎相关研究

罗氏公司7月10日宣布，由于安全性和有效性不佳，已终止阿格列扎(aleglitazar)的临床试验。该药物属于过氧化酶体增殖物激活受体(PPAR)双重激动剂，罗氏一直致力于将其开发为既能控制血糖、又能降低心血管风险的2型糖尿病新药。

声明指出，一个独立的数据和安全监测委员会(DSMB)提出了终止AleCardio研究(2型糖尿病伴新发急性冠脉综合症患者阿格列扎Ⅲ期临床研究)的建议，罗氏基于这一建议终止了该研究。该公司还同时决定终止该药物的其他所有研究。

该公司发言人称：“虽然Ⅱ期数据支持阿格列扎在减少2型糖尿病患者心血管事件方面的潜在益处，但AleCardio 试验结果显示其有效性不足且增加骨折、肾脏损害及心衰等不良事件的发生率，导致收益/风险评估结果不佳。”

罗氏首席医学官、全球产品开发总监Hal Barron博士在声明中指出，“我们原本希望阿格列扎能够为伴有心血管疾病风险的2型糖尿病患者带来明显益处，但试验结果令人失望。”该公司正与研究者一道，继续为参与研究的患者提供治疗，并将阿格列扎转换为其他降糖药物。

罗氏在2009年6月宣布阿格列扎III期试验启动时，曾声称该药是一种 “专为降低高风险2型糖尿病患者心血管疾病发病率和死亡率而设计的独特产品”。该公司声明指出，SYNCHRONY研究(安慰剂对照剂量范围Ⅱ期研究)结果显示，阿格列扎对于2型糖尿病患者“具有稳定的降脂和降糖协同作用，且具有良好的安全性和耐受性”。

根据罗氏在AleCardio研究结束时发布的有关声明，该公司将对研究数据进行分析并在医学会议上公布分析结果。

阿格列扎作为PPAR双重激动剂，同时活化PPAR-α和PPAR-γ。截至7月10日，clinicaltrials.gov网站显示，有关阿格列扎的9项研究或正在招募受试者或已启动但尚未招募受试者。

SYNCHRONY研究结果已于2009年正式发表在《柳叶刀》杂志上(Lancet 2009;374:126-35)。

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By: ELIZABETH MECHCATIE, Cardiology News Digital Network

Citing "safety signals and lack of efficacy," Roche has announced that it is terminating clinical trials of aleglitazar, a dual PPAR agonist that the company had been pursuing as a treatment for type 2 diabetes that lowered cardiovascular risk in addition to controlling glucose.

In a statement on July 10, the company said that the decision was based on a recommendation of the independent Data and Safety Monitoring Board (DSMB) to halt the AleCardio study, a phase III study of aleglitazar in patients with type 2 diabetes and a recent acute coronary syndrome event. The company also has decided to terminate all other studies of the drug.

"While phase II data supported the investigation of the potential benefit of aleglitazar in reducing cardiovascular events in type II diabetes, a lack of efficacy and an increased rate of adverse events including fractures, renal impairment and heart failure were seen in the AleCardio trial, resulting in an unfavorable benefit/risk profile," a company spokesperson said.

"We are disappointed by this outcome as we hoped that aleglitazar would provide significant benefit for patients with type 2 diabetes who are at risk of cardiovascular disease," Dr. Hal Barron, Roche’s chief medical officer and head of global product development, said in the statement. The company "is working with investigators to support the management of patients and their transition from aleglitazar treatment to other blood sugar control therapies," he added.

When the company announced the launch of phase III trials of aleglitazar in June 2009, the drug was described in a Roche statement as "uniquely designed to reduce cardiovascular morbidity and mortality" in high-risk patients with type 2 diabetes. The statement said that the results of SYNCHRONY, a phase II, placebo-controlled dose-ranging study, showed that aleglitazar "had a balanced synergistic effect on both lipid and glucose control with a good safety and tolerability profile" in type 2 diabetes patients.

Roche plans to analyze the data from the AleCardio study and will present the results at a medical meeting, according to the statement announcing the end of the study.

Aleglitazar is a peroxisome proliferator–activated receptor (PPAR) co-agonist, activating both PPAR-alpha and PPAR-gamma. As of July 10, nine studies of aleglitazar were listed as either recruiting or as active and not recruiting on clinicaltrials.gov.

The results of the SYNCHRONY study were published in 2009 (Lancet 2009;374:126-35).