Memorandum

Sanofi releases topline phase 3 EDITION III, IV, JPI results for U300 insulin glargine – December 4, 2013

Executive Highlights

  • EDITION III, IV, and JPI all meet their primary A1c endpoints of similar glycemic control vs. Lantus.
  • Severe and confirmed nocturnal hypoglycemia benefit seen in EDITION I and II was not preserved in EDITION III; hypoglycemia analyses for EDITION IV and JPI are ongoing.
  • Sanofi reaffirms 1H14 FDA submission.

Sanofi released topline results for its U300 insulin glargine's phase 3 EDITION III, IV, and JPI trials concurrently with the presentation of full EDITION II results at IDF Day #2. EDITION III (n=878) enrolled people with type 2 diabetes and inadequate glycemic control on oral antidiabetic medications and no previous insulin treatment. It met its primary endpoint of comparable A1c reductions from baseline to six months for U300 vs. Lantus (1.42% vs. 1.46% reductions, respectively; baseline not specified). However, in contrast to EDITION I and II, there were no significant reductions in the rate of severe or confirmed nocturnal hypoglycemia in months three to six of EDITION III (15.5% vs. 17.4% on U300 and Lantus, respectively). Differences in patient population for EDITION I and II compared to III may explain the differences in hypoglycemia results - I and II enrolled difficult-to-treat type 2 patients (mean 12-15 years diabetes duration, >42u insulin requirement/day), while EDITION III enrolled patients who presumably had less severe diabetes (though disease duration was not specified) and had never been on insulin before. It may be that the hypoglycemia benefit of U300 does not become evident until it is used in patients already more prone to hypoglycemia. EDITION IV (n=549) and JPI (n=243) were both conducted in people with type 1 diabetes on background basal-bolus therapy. EDITION IV was conducted globally while JPI was only in Japan. Both studies met the primary endpoint of similar A1c reductions compared to Lantus at six months (EDITION IV: ~0.4% reduction in both arms; EDITION JPI: 0.3% for U300 and 0.4% for Lantus; baselines not specified). Oddly, severe and nocturnal hypoglycemia from month three to six was not a pre-specified endpoint in these studies. Full results for EDITION III, IV, and JPI are expected to be presented at conferences in 2014, and Sanofi reaffirmed its guidance to submit the U300 glargine to the US FDA in 1H14. As a reminder, EDITION I was the first of the program to report full results (at ADA 2013), showing a 21% reduction in nocturnal hypoglycemia compared to Lantus. EDITION II reported topline results at that time and full results here at IDF. The final trial that has yet to report is EDITION JPII. Merck, BI/Lilly, and Biocon are also working on biosimilar insulin glargine formulations, though data on these candidates have been limited to date.

 

-- by Jessica Dong and Kelly Close