赛诺菲新胰岛素U300 4个III期研究达主要终点

赛诺菲（Sanofi）12月3日公布了实验性新胰岛素U300的III期研究（EDITION II）的全部数据。研究结果表明，与来得时（Lantus，insulin glargine，甘精胰岛素）相比，U300表现出了相似的血糖控制，同时经历夜间低血糖的患者比例下降23%，达到了研究的主要终点。

EDITION II的全部数据已于12月3日提交至在澳大利亚墨尔本举行的国际糖尿病联盟2013年世界糖尿病大会。EDITION II研究的结果与EDITION I研究一致，这2项研究均在已经在使用基础胰岛素（联合餐食胰岛素或口服药物）的2型糖尿病患者中开展。

赛诺菲也公布了EDITION III期临床项目的额外顶级结果，EDITION III、EDITION IV、EDITION JP I研究均达到了主要终点。全部的结果将提交至2014年的科学会议。

赛诺菲计划于2014年上半年向FDA和EMA提交U300的监管申请文件。

关于U300：

U300是一种实验性新胰岛素，是基于来得时（Lantus）生物实体甘精（glargine ）分子的一种新配方，同时具有甘精完善的疗效和安全性。U300具有独特的药代动力学和药效学属性，相关研究已经证明，与Lantus相比，U300具有更平坦和更长效的属性。此外，与Lantus相比，U300也提供了更小体积皮下注射剂型的益处。

英文原文：Sanofi Announces New Phase 3 Results for Investigational New Insulin U300
- EDITION II trial demonstrates similar blood sugar control with fewer night-time low blood sugar events for U300 compared with Lantus® -

- EDITION III, IV and JP I studies meet primary endpoint -

PARIS, Dec. 3, 2013 /PRNewswire/ -- Sanofi announced the full results from the EDITION II study showing that investigational new insulin U300 demonstrated similar blood sugar control with 23% fewer patients experiencing night-time low blood sugar compared with Lantus? (insulin glargine [rDNA origin] injection). These results were presented today at the International Diabetes Federation 2013 World Diabetes Congress in Melbourne, Australia. The full EDITION II results are consistent with those from EDITION I.1 Both studies were conducted in people with type 2 diabetes already using basal insulin (with mealtime insulin or oral medication).

Sanofi also announced today additional topline results from the EDITION Phase 3 clinical program. The primary endpoint was met in the 6-month EDITION III, EDITION IV and EDITION JP I studies. Full results will be presented at scientific meetings in 2014.

"We are encouraged by these results which suggest that U300 could be a viable treatment option for a wide range of people with type 1 and type 2 diabetes," commented Pierre Chancel, Senior Vice President, Global Diabetes, Sanofi.

EDITION II Full Results

EDITION II included type 2 diabetes patients, who failed to control their blood sugar levels on previous basal insulin and oral medication, together with a long duration of disease and high body mass index (BMI).  The study randomized 811 participants (1:1) to U300 (n=404) or Lantus? (n=407) once daily in the evening, while continuing oral anti-diabetics.

EDITION II met its primary endpoint by showing similar reductions in HbA1c from baseline between U300 and Lantus? at 6 months [least squares mean change -0.57% (0.09) and -0.56% (0.09), respectively; difference -0.01% (95% CI: -0.14 to +0.12)] in people with type 2 diabetes who had challenging baseline characteristics (mean age of study participants: 58.2 years; duration of type 2 diabetes: 12.6 years; BMI: 34.8 kg/m2; HbA1c: 8.24 %; basal insulin dose: 0.67 U/kg at baseline).

The percentage of participants with severe or confirmed (defined by plasma glucose less than or equal to 70 mg/dL) night-time low blood sugar levels (nocturnal hypoglycemia) from month 3 to 6 was significantly lower with U300 vs. Lantus? [21.6% vs. 27.9%; relative risk (RR) 0.77 (95% CI: 0.61 to 0.99); p=0.038]. Over the 6-month treatment period, the incidence of any nocturnal hypoglycemia (% of participants with greater than or equal to 1 event) was lower with U300 vs. Lantus? [30.5% vs. 41.6%; RR 0.73 (95% CI: 0.60 to 0.89)] as was the incidence of any hypoglycemic event at any time of the day (over a 24 hour period) [U300: 71.5%; Lantus?: 79.3%; RR 0.90 (95% CI: 0.84 to 0.97)]. This result was also obtained across the entire 6-month study period, including the first 8 weeks of the trial.

There were similar findings between groups for adverse events, including injection site reactions and hypersensitivity reactions.

"Reducing the risk of hypoglycemic events is imperative for effective management of diabetes, and EDITION II suggests that U300 reduces the risk of these events, even in a challenging patient population who have been on high basal insulin doses and oral medications without being able to achieve their treatment targets," said Hannele Yki-Jarvinen, Professor of Medicine, University of Helsinki, Finland.

The EDITION II abstract is titled: An investigational new insulin U300: glucose control and hypoglycemia in people with type 2 diabetes on basal insulin and OADs (EDITION II) (Yki-Jarvinen et al. Oral presentation, 3rd December 2013 10:45 ? 12:45 [ABS OP-0075]).

EDITION III topline results (study in insulin-naive people with type 2 diabetes)

EDITION III compared U300 with Lantus? in 878 people with type 2 diabetes not previously treated with insulin and uncontrolled on oral medication. The primary endpoint of similar blood sugar level control (measured by HbA1c) from baseline to month 6 was met (-1.42% [95% CI: -1.511 to -1.326] in the U300 group, and -1.46% [95% CI: -1.555 to -1.367] in the Lantus? group).

Consistent with the results of the EDITION I and II studies, the rates of severe or nocturnal confirmed hypoglycemia in EDITION III from month 3 to 6 (main secondary endpoint) were lower with U300 (15.5% for U300 vs. 17.4% for Lantus?), but unlike EDITION I and II, the reduction was not statistically significant. Overall incidence of any documented hypoglycemia during the entire 6-month treatment period was numerically lower in the U300 group than in the Lantus? group (49.9% vs. 55.3%; no statistical analysis was performed.)

EDITION IV and EDITION JP I topline results (studies in people with type 1 diabetes)

EDITION IV and JP1 studies compared U300 with Lantus? in people with type 1 diabetes treated with basal and mealtime insulin. EDITION IV enrolled 549 patients internationally, while EDITION JP I was conducted in 243 Japanese patients. The primary endpoint was met in both studies which showed similar reductions in HbA1c from baseline between U300 and Lantus? at 6 months. (EDITION IV: -0.40% [95% CI: -0.501 to -0.299] in the U300 group, and -0.44% [95% CI: -0.543 to -0.344] in the Lantus? group); EDITION JP I: -0.30% [95% CI: -0.411 to -0.183] in the U300 group, and -0.43% [95% CI: -0.542 to -0.313] in the Lantus? group).

In EDITION IV and EDITION JP I, confirmed and severe nocturnal hypoglycemia from month 3 to 6 was not pre-specified as a main secondary endpoint per study protocol. Analyses of several hypoglycemia categories are underway and will be presented, together with the EDITION III full results, at medical congresses in the first half of 2014.

In all of the studies, no differences in other adverse events were observed between U300 and Lantus?.

Sanofi anticipates the regulatory submissions to U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in the first half of 2014.

About the EDITION Phase 3 program

The EDITION program is a worldwide and comprehensive series of Phase 3 studies evaluating the efficacy and safety of new insulin U300 in broader and diverse populations of people with diabetes. The full EDITION I (basal insulin + mealtime insulin) results have already been released.1 The full EDITION II (basal insulin + oral therapy) results were presented at WDC 2013. Full results from EDITION III, EDITION IV, EDITION JP I, and EDITION JP II (Japanese type 2 diabetes patients treated with basal insulin + oral therapy) will be presented at scientific meetings in 2014.

About investigational new insulin U300

Investigational new insulin U300 is a new formulation based on the glargine molecule, the biological entity of Lantus?, with its well established efficacy and safety profile. U300 has unique pharmacokinetic and pharmacodynamic profiles with studies demonstrating it has even flatter and more prolonged profiles than Lantus?.2-5 U300 also offers the benefit of a smaller volume of subcutaneous injection compared with Lantus?.

About Lantus (insulin glargine [rDNA origin] injection)

Prescription Lantus is a long-acting insulin used to treat adults with type 2 diabetes and adults and patients (6 years and older) with type 1 diabetes for the control of high blood sugar.  It should be taken once a day at the same time each day to lower blood glucose.

Do not use Lantus to treat diabetic ketoacidosis.