Studies Show Investigational New Insulin Glargine Product from Lilly and Boehringer Ingelheim Similar in Safety and Efficacy to Lantus®

Companies present comprehensive data for LY2963016*, new insulin glargine product

BURLINGTON and TORONTO, ON, June 16, 2014 /CNW/ - For the first time today, Eli Lilly and Company and Boehringer Ingelheim Pharmaceuticals Inc. presented data showing that LY2963016*, the alliance's investigational new insulin glargine product, has a similar safety and efficacy profile to currently marketed insulin glargine (Lantus^®).^1,2,3,4,5,6 Results from these Phase I and Phase III studies were presented at the 74^th American Diabetes Association Scientific Sessions in San Francisco.

"Results from six completed clinical trials for this new insulin glargine product showed that it works similarly in the body and produces clinical results similar to Lantus," said Tom Blevins, M.D., endocrinologist with Texas Diabetes & Endocrinology, Austin, TX. "These data are important because Lilly/BI's insulin glargine could serve as an important treatment option in the future when physicians are deciding on an insulin glargine product to help patients meet their treatment goals."

LY2963016* insulin glargine is an investigational basal insulin that is intended to provide long-lasting blood sugar control between meals and at night, an integral part of glycemic control.⁷ It has the same amino acid sequence as Lantus^®.

Phase III Study Results

In patients with type 1 and type 2 diabetes, LY2963016* insulin glargine was compared to currently marketed insulin glargine, and both products led to significant decreases in average blood glucose levels (HbA1c). LY2963016* insulin glargine demonstrated non-inferiority compared to marketed insulin glargine, and marketed insulin glargine demonstrated non-inferiority to LY2963016* insulin glargine.^4,5

• Patients with type 1 diabetes had HbA1c reductions of -0.4 per cent (LY2963016* insulin glargine) and -0.5 per cent (marketed insulin glargine) at 24 weeks, with similar results at 52 weeks (-0.3 per cent for both insulin glargine treatments).⁴
• Patients with type 2 diabetes had HbA1c reductions of -1.3 per cent in both insulin glargine treatment groups at 24 weeks.⁵

Approximately one-third of patients with type 1 diabetes reached target HbA1c levels of less than 7 per cent at 24 weeks with LY2963016* insulin glargine (35 per cent) and marketed insulin glargine (32 per cent) treatment.⁴ In patients with type 2 diabetes, about half of patients reached these target levels with LY2963016* insulin glargine (49 per cent) and marketed insulin glargine (53 per cent) treatment.⁵

In patients with type 1 diabetes, the incidence of adverse events at 52 weeks was the same between the two insulin treatments (62 per cent). The total average hypoglycaemia rate (having symptoms attributable to a low blood sugar level and/or blood glucose less than or equal to 3.88 mmol/L) at 24 weeks was also similar between LY2963016* insulin glargine and marketed insulin glargine (87 and 89 events/patient/year, respectively).⁴

The frequency of adverse events was similar between the two treatments in patients with type 2 diabetes (52 per cent and 48 per cent, LY2963016* insulin glargine and marketed insulin glargine, respectively), including the total average hypoglycaemia rate (21 vs. 22 events/patient/year, LY2963016* insulin glargine and marketed insulin glargine, respectively).⁵

The Phase III studies also evaluated whether LY2963016* insulin glargine and marketed insulin glargine led to similar development of insulin antibodies and similar effects of immune responses on clinical outcomes. Results showed a similar immunogenicity profile of LY2963016* insulin glargine to marketed insulin glargine.

• The proportion of patients with type 1 diabetes with detectable anti-insulin antibodies was similar between LY2963016* insulin glargine and marketed insulin glargine at baseline (17 per cent and 21 per cent, respectively) and throughout treatment to 52 weeks (40 per cent and 39 per cent, respectively).
• The proportion of patients with type 2 diabetes with detectable insulin antibodies was similar between LY2963016* insulin glargine and marketed insulin glargine at baseline (6 per cent and 4 per cent, respectively) and throughout treatment to 24 weeks (15 per cent and 11 per cent, respectively).
• Clinical outcomes, including HbA1c levels, basal insulin dose and total hypoglycaemia levels, were not affected by whether or not patients developed antibodies response during the study.⁶

Phase I Study Results

Results from Phase I studies showed that LY2963016* insulin glargine and marketed insulin glargine have similar pharmacokinetic (PK) and pharmacodynamic (PD) profiles, meaning that LY2963016* insulin glargine, when injected under the skin, provided the same amount of insulin in the blood, with similar characteristics and insulin action (how insulin works to control blood glucose levels), compared to marketed insulin glargine.^1,2

• The PK and PD of LY2963016* insulin glargine and the EU- and US-approved versions of insulin glargine were compared in three studies of healthy participants who received 0.5U/kg doses of two different insulin glargine products on two separate occasions. Results showed similar PK and PD properties of LY2963016* insulin glargine and marketed insulin glargine.¹  
• The PK and PD properties were similar between LY2963016* insulin glargine and marketed insulin glargine and were consistent across both administered doses in a study comparing the two insulin treatments at two different doses (0.3 and 0.6 U/kg) in healthy participants.²

In these Phase I studies, LY2963016* insulin glargine was well-tolerated, with no safety concerns noted in adverse events, clinical laboratory tests, vital signs or ECG data. The frequency of adverse events reported was similar between the two treatments.^1,2

A further Phase 1 study assessed LY2963016* insulin glargine's duration of action (how long the insulin works to control blood glucose levels) in patients with type 1 diabetes. Results showed that the average duration of action was 24 and 26 hours for LY2963016* insulin glargine and marketed insulin glargine, respectively. LY2963016* insulin glargine was well-tolerated, with no safety concerns noted in adverse events, clinical laboratory tests, vital signs or ECG data. The frequency of adverse events reported was similar between the two treatments.³

About the Phase III Studies

ELEMENT-1 was a 52-week Phase III, randomized, open-label study of 535 patients with type 1 diabetes. The primary objective was to evaluate whether LY2963016* insulin glargine was non-inferior to currently marketed insulin glargine in reducing average blood sugar levels (HbA1c) from baseline at 24 weeks. Patients in the study were also treated with mealtime insulin. Anti-insulin glargine antibodies were also measured to determine the immunogenicity profile of LY2963016* insulin glargine.^4,6

ELEMENT-2 was a 24-week Phase III, randomized, double-blind study of 756 patients with type 2 diabetes. The primary objective was to evaluate whether LY2963016* insulin glargine was non-inferior to currently marketed insulin glargine in reducing average blood sugar levels (HbA1c) from baseline at 24 weeks in patients inadequately controlled on two or more oral diabetes medicines. Anti-insulin glargine antibodies were also measured to determine the immunogenicity profile of LY2963016* insulin glargine.^5,6

About the Phase I Studies

The pharmacokinetics (PK) and pharmacodynamics (PD) of LY2963016* insulin glargine and the EU- and US-approved versions of insulin glargine were evaluated in three Phase I, randomized, double-blind, cross-over replicate euglycemic clamp studies in healthy participants. There was a minimum washout period of one week to separate the doses. Blood samples were collected pre-dose and up to 24 hours post-dose to assess PK, and a euglycemic clamp lasting up to 24 hours was used to assess PD after administration of study insulin at 0.5 U/kg.¹

The PK and PD of two other doses of LY2963016* insulin glargine and currently marketed insulin glargine (0.3 and 0.6 U/kg) were also assessed in a Phase I, randomized, subject- and investigator-blinded study. Twenty-four healthy participants randomly received one of four dosing sequences, receiving a total of two doses each of LY2963016* insulin glargine and currently marketed insulin glargine. There was a minimum washout period of six days to separate the doses. Blood samples were collected pre-dose and up to 24 hours post-dose to assess PK, and a euglycemic clamp lasting up to 24 hours was used to assess PD.²

A Phase I randomized, double-blind, crossover glucose clamp study assessed the duration of action of LY2963016* insulin glargine and currently marketed insulin glargine in 20 fasted males with type 1 diabetes. Patients received single administered doses of 0.3 U/kg of both insulin treatments, with a minimum washout period of one week to separate the doses. Duration of action was assessed with a euglycemic clamp lasting up to 42 hours post-dose.³

About Diabetes

An estimated 382 million people worldwide have type 1 or type 2 diabetes.⁸ Type 2 diabetes is the most common type, accounting for an estimated 90 per cent of all diabetes cases.⁹ Diabetes is a chronic condition that occurs when the body either does not properly produce, or use, the hormone insulin.¹⁰ Today, more than 9 million Canadians live with diabetes or prediabetes - a condition that, if left unchecked increases the risk of developing type 2 diabetes.¹¹

Boehringer Ingelheim and Eli Lilly and Company

In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in diabetes that centers on compounds representing several of the largest diabetes treatment classes. The alliance leverages the strengths of two of the world's leading pharmaceutical companies. By joining forces, the companies demonstrate commitment in the care of patients with diabetes and stand together to focus on patient needs. Find out more about the alliance at www.boehringer-ingelheim.com or www.lilly.com.

About Boehringer Ingelheim (Canada) Ltd.

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally with 142 affiliates and a total of more than 47,400 employees. The focus of the family-owned company, founded in 1885, is researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.

Taking social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects, such as the initiative "Making more Health" and caring for the employees. Respect, equal opportunities and reconciling career and family form the foundation of the mutual cooperation. In everything it does, the company focuses on environmental protection and sustainability.

In 2013, Boehringer Ingelheim achieved net sales of about 14.1 billion euros. R&D expenditure corresponds to 19.5% of its net sales.

The Canadian headquarters of Boehringer Ingelheim was established in 1972 in Montreal, Quebec and is now located in Burlington, Ontario. Boehringer Ingelheim employs more than 550 people across Canada.

For more information please visit www.boehringer-ingelheim.ca

About Lilly Diabetes

Lilly has been a global leader in diabetes care since 1923, when we introduced the world's first commercial insulin. Today we are building upon this heritage by working to meet the diverse needs of people with diabetes and those who care for them. Through research and collaboration, a broad and growing product portfolio and a continued determination to provide real solutions—from medicines to support programs and more—we strive to make life better for all those affected by diabetes around the world. For more information, visit www.lillydiabetes.com.

About Eli Lilly Canada Inc.

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Indiana, Lilly provides answers – through medicines and information – for some of the world's most urgent medical needs. Eli Lilly Canada, headquartered in Toronto, Ontario, employs close to 500 people across the country. Additional information about Eli Lilly Canada can be found at www.lilly.ca.

REFERENCES

1. Linnebjerg, H, Lam E, et al. Comparative Pharmacokinetics (PK) and Pharmacodynamics (PD) of LY2963016 Insulin Glargine and EU- and US-approved Versions of Lantus® Insulin Glargine in Healthy Subjects. Abstract 889-P. Presented at 74th American Diabetes Association (ADA) Scientific Sessions; June 13-17, 2014; San Francisco, CA.
2. Zhang, X, Lam, E, et al. Comparative Pharmacokinetics and Pharmacodynamics of Two Insulin Glargine Products, LY2963016 and Lantus®, in Healthy Subjects at Two Dose Levels. Abstract 890-P. Presented at 74th American Diabetes Association (ADA) Scientific Sessions; June 13-17, 2014; San Francisco, CA.
3. Heise, T, Zhang, X, et al. Duration of Action of 2 Insulin Glargine Products, LY2963016 and Lantus®, in Subjects with Type 1 Diabetes Mellitus (T1DM). Abstract 891-P. Presented at 74th American Diabetes Association (ADA) Scientific Sessions; June 13-17, 2014; San Francisco, CA.
4. Blevins, T, Dahl, D, et al. Similar Efficacy and Safety with LY2963016 Insulin Glargine Compared with Lantus® Insulin Glargine in Patients with T1D: the ELEMENT 1 Study. Abstract 69-OR. Presented at 74th American Diabetes Association (ADA) Scientific Sessions; June 13-17, 2014; San Francisco, CA.
5. Rosenstock, J, Hollander, P, et al. Similar Efficacy and Safety with LY2963016 Insulin Glargine Compared with Lantus® Insulin Glargine in Patients with T2D: the ELEMENT 2 Study. Abstract 64-OR. Presented at 74th American Diabetes Association (ADA) Scientific Sessions; June 13-17, 2014; San Francisco, CA.
6. Deeg, M, Ilag, L, et al. Evaluation of Immunogenicity of LY2963016 Insulin Glargine Compared with Lantus® Insulin Glargine in Patients with T1D or T2D. Abstract 70-OR. Presented at 74th American Diabetes Association (ADA) Scientific Sessions; June 13-17, 2014; San Francisco, CA.
7. Inzucchi SE, Bergenstal RM, et al. Management of Hyperglycemia inType2 Diabetes: A Patient-Centered Approach. Diabetes Care June 2012 vol. 35 no. 6 1364-1379.
8. International Diabetes Federation. IDF Diabetes Atlas, 6th edn. Brussels, Belgium: International Diabetes Federation, 2013. http://www.idf.org/diabetesatlas.
9. Canadian Diabetes Association. What is Diabetes? Available at http://www.diabetes.ca/about-diabetes/what-is-diabetes Accessed on June 6, 2014.
10. International Diabetes Federation. IDF Diabetes Atlas, 6th edn. Brussels, Belgium: International Diabetes Federation, 2013. http://www.idf.org/diabetesatlas.
11. Canadian Diabetes Association. About Diabetes. Available at http://www.diabetes.ca/about-diabetes Accessed on: June 6, 2014

Lantus® is a registered trademark of Sanofi

* LY2963016 insulin glargine is an investigational compound. It's safety and efficacy has not yet been established and is currently not authorized for sale in Canada

SOURCE: Boehringer Ingelheim (Canada) Ltd.

For further information: Jennifer Mota, Brand Communication Associate, Boehringer Ingelheim (Canada) Ltd., Email: [e-mail], Phone: [phone]; Helen Stone, Manager, Communications, Eli Lilly Canada Inc., Email: [e-mail], Phone: [phone]