Clinical Trials

EDITION I: As the first study of the EDITION Phase 3 program, EDITION I evaluated the efficacy and safety of new insulin U300, vs. Lantus® in people with type 2 diabetes using basal plus mealtime insulin. In a multicenter, open-label study 807 people were randomized (1:1) to once daily evening new insulin U300 (n=404) or Lantus® (n=403) while continuing mealtime insulin. The basal insulin was titrated to achieve fasting plasma glucose of 80-100 mg/dL. Primary endpoint was change in HbA1c from baseline to month 6, and main secondary endpoint was % of people with at least 1 severe or confirmed nocturnal hypoglycemic event from month 3 to month 6. (NCT01499082)
EDITION II is a 6-month, multicenter, randomized, open-label, parallel-group study comparing the efficacy and safety of a new formulation of insulin glargine and Lantus® both in combination with oral antihyperglycemic drug(s) in patients with type 2 diabetes mellitus with a 6 month safety extension period (NCT01499095). 
EDITION JP I is a 6-month, multicenter, randomized, open-label, parallel-group study comparing the efficacy and safety of a new formulation of insulin glargine and Lantus® in Japanese patients with type 1 diabetes mellitus with a 6 month safety extension period. (NCT01689129)
EDITION JP II is a 6-month, multicenter, randomized, open-label, parallel-group study comparing the efficacy and safety of a new formulation of insulin glargine and Lantus®both in combination with oral antihyperglycemic drug(s) in Japanese patients with type 2 diabetes mellitus with a 6 month safety extension period. (NCT01689142)

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. 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.

* On June 6, 2015, Sanofi announced results from the EDITION JP 1 and EDITION JP 2 extension studies where Japanese participants (with type 1 and type 2 diabetes, respectively) received Toujeo®(insulin glargine [rDNA origin] injection, 300 U/mL) or Lantus® (insulin glargine [rDNA origin] injection, 100 U/mL) treatment for a total of 12 months. Over this entire study period, Toujeo maintained similar blood sugar control, with fewer people experiencing night-time low blood sugar events (blood sugar levels <= 54 mg/dL in the study with people with type 1 diabetes, and <= 70 mg/dL in the study with people with type 2 people), compared with Lantus. These new results from EDITION JP 1 and 2 were presented at the 75th Scientific Sessions of the American Diabetes Association.

"The results of the EDITION JP 1 and 2 extension studies reaffirm the clinical benefit that Toujeo can bring to people who are living with uncontrolled diabetes", said Pierre Chancel, Senior Vice President, Head of Global Diabetes, Sanofi. "As a new addition to our portfolio, Toujeo gives patients a further option to help them reach their glycemic goals, and demonstrates our commitment to providing innovative therapies to enhance diabetes care."

In Japanese people with uncontrolled type 1 diabetes (EDITION JP 1), confirmed night-time low blood sugar (<=70 mg/dL) event rates and percentage of participants experiencing >=1 event over the 12-month study period were comparable in both groups. However, hypoglycemic event rate at the lower threshold (<54 mg/dL) was 38% lower with Toujeo. Risk reduction of night-time low blood sugar events at this threshold showed that 21% fewer patients experienced night-time low blood sugar events with Toujeo vs. Lantus.

In Japanese people with type 2 diabetes uncontrolled on basal insulin and oral anti-diabetics (EDITION JP 2), incidence of low blood sugar events at night-time (blood sugar levels <= 70 mg/dL) was also reduced (27% fewer patients experiencing >=1 event over 12-month study period). Event rates (per patient-year) of low blood sugar at night-time and any time of the day (over 24 hours) were consistently lower with Toujeo compared with Lantus. Over the 12-month period, people with type 2 diabetes treated with Toujeo and oral medications also saw a slight reduction in body weight, in comparison to those treated with Lantus who saw a slight increase.

"The additional data from the EDITION JP 2 study demonstrate Toujeo's ability to achieve sustainable glycemic control in the Japanese type 2 population," commented Yasuo Terauchi, Principal Investigator of the EDITION JP 2 study and Professor at Yokohama City University School of Medicine, Kanagawa. "The reduction in episodes of hypoglycemia observed and the additional weight findings demonstrated in EDITION JP 2 mean that Toujeo has the potential to help the people with type 2 diabetes in Japan to start and remain on insulin therapy in order to reach their long-term targets."

The abstracts are titled:

Sustained Glycemic Control and Less Nocturnal Hypoglycemia with New Insulin Glargine 300 U/mL compared with Glargine 100 U/mL over 12 Month in Japanese People with T1DM l (EDITION JP 1). (Matsuhisa M et al. Presentation 987-P, June 6, 2015).

New Insulin Glargine 300 U/mL Provides Sustained Glycemic Control and Reduced Hypoglycemia over 12 Months Compared with Glargine 100 U/mL in Japanese People with T2DM Managed with Basal Insulin plus OAD(s) (EDITION JP 2). (Terauchi Y et al. Presentation 98-OR, June 6, 2015).

EDITION JP 1 Full Results with 6 Month Extension1

In EDITION JP 1 (n=228), Japanese people with type 1 diabetes that continued to receive treatment for an additional 6 months showed comparable blood sugar level control (reduction in HbA1C and FPG) from baseline between Toujeo and Lantus at 12 months (mean [SD] change -0.20 [0.80] % and -14.0 [86.5] mg/dL and (mean [SD] change -0.25 [0.72] % and -7.0 [93.2] mg/dL respectively).

The percentages of participants with >=1 severe or confirmed (defined as plasma glucose <=70 mg/dL) night-time low blood sugar event over the 12-month study period were comparable between groups. At the lower <54 mg/dL threshold, a reduction in event rate was observed with Toujeo compared with Lantus during the night (rate ratio 0.62; 95% CI: 0.39 to 0.97). The percentage of participants experiencing >=1 nocturnal event at this threshold was also reduced with Toujeo compared with Lantus (relative risk 0.79; 95% CI: 0.64 to 0.98). Severe hypoglycemia occurred in 12 and 11 participants receiving Toujeo and Lantus respectively. There were similar findings between groups for adverse events.

EDITION JP 2 Full Results with 6 Month Extension2

In EDITION JP 2 (n=222), Japanese people with type 2 diabetes who failed to control their blood sugar levels on previous basal insulin and oral medication, and continued to receive treatment for an additional 6 months, showed similar blood sugar level control (reduction in HbA1C and FPG) from baseline between Toujeo and Lantus at 12 months (mean [SD] change -0.28 [0.84] % and -12.1 [56.6] mg/dL, and mean [SD] change -0.33 [0.79] % and -18.6 [43.3] mg/dL respectively).

The percentage of participants with >=1 severe or confirmed (defined as plasma glucose <=70 mg/dL) low blood sugar event at night-time over the 12-month treatment period was lower with Toujeo vs. Lantus (relative risk 0.73; 95% CI: 0.55 to 0.97). There were also consistently fewer nocturnal and at any-time (24 hours) confirmed (<=70 mg/dL) or severe hypoglycemic events per patient-year seen with Toujeo compared with Lantus (rate ratio 0.41; 95% CI: 0.18 to 0.92; rate ratio 0.64; 95% CI: 0.44 to 0.94, respectively). Severe hypoglycemia was rare with only 3 and 2 events reported for Toujeo and Lantus respectively.

In addition, the patients treated with Toujeo lost some weight, compared with a slight increase in the Lantus group (-0.7 kg vs. 0.5 kg respectively; NS). There were similar findings between groups for adverse events.

* On December 3, 2013, Sanofi announced the full results from the EDITION II study showing that  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 at the International Diabetes Federation 2013 World Diabetes Congress in Melbourne, Australia. The full EDITION II results are consistent with those from EDITION I. Both studies were conducted in people with type 2 diabetes

already using basal insulin (with mealtime insulin or oral medication).

Sanofi also announced additional top-line 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.

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 ?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 ?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.

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-Järvinen et al. Oral presentation, 3rd December 2013 10:45 ? 12:45 [ABS OP-0075]).

EDITION III top-line results (study in insulin-naïve 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 top-line 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.

reduction while fewer patients experienced night-time low blood sugar events compared with Lantus®.
These results are from EDITION I and EDITION II respectively and are part of the EDITION Phase 3 clinical program evaluating the efficacy and safety of the investigational new insulin U300 in people with diabetes. The EDITION I data was presented at the 73rd Scientific Sessions of the American Diabetes Association. EDITION I demonstrated similar reductions in HbA1c (glycated hemoglobin) from baseline (primary endpoint) between new insulin U300 and Lantus® at 6 months [least squares mean change -0.83% (0.06) in both groups; difference -0.00% (95% CI -0.11 to 0.11)] in people with type 2 diabetes who had challenging treatment needs (mean age of study participants: 60 years; duration of type 2 diabetes: 15.8 years; BMI: 36.6 kg/m2; HbA1c: 8.15 %; total insulin dose: 1.2 U/kg; basal insulin dose: 0.67 U/kg at baseline). In addition, approximately 40% of study participants with uncontrolled glycemic (blood sugar) levels despite receiving a combined therapy (oral antidiabetic agents plus 2/4 basal and prandial insulins) reached glycemic control (HbA1c <7%) at month 6 both in the new insulin U300 (39.6%) and in the Lantus®arm (40.9%).

The investigational new insulin U300 was associated with a 21% reduction in severe or confirmed nocturnal hypoglycemia (low blood sugar) from month 3 to month 6. Significantly fewer patients had nocturnal (severe and/or confirmed; i.e. ?70 mg/mL) hypoglycemia (low blood sugar) during months 3 to 6 (pre-specified main secondary endpoint: 36.1% vs. 46.0%; RR 0.79; p=0.0045) and the occurrence of any nocturnal hypoglycemic event (% of people with at least one event) during the 6-month study period was lower on new insulin U300 during the study period compared to the Lantus® group (45.3% vs. 59.7%; RR 0.76; 95% CI 0.66 to 0.87). New insulin U300 was welltolerated in this study, with no differences in other adverse events observed from Lantus®.