1. Abasaglar® (insulin glargine): research revealed
Adverse events should be reported. Reporting forms and information can be found at Adverse events and product complaints should also be reported to Lilly: please call Lilly UK on
Prescribing information is available at the end of this presentation.
August UK/GLA/00102

2. Introduction to biosimilars and Abasaglar® PK/PD data
Part 1: Biosimilars
Introduction to biosimilars and Abasaglar® PK/PD data

3. 1922 1923 1963 Insulin molecule isolated1
Lilly: first commercially available insulin for human use1
Synthetic insulin produced2
Rosenfeld L. Clin Chem 2002; 48(12): 2270–2288.
Lasker S et al. J Diabet 2010; 1: 1-8.

4. 1979
1982
1996
Genentech: first commercial production of recombinant human insulin2,3
Lilly: first recombinant human insulin (Humulin) approved for use4,5
Lilly: first human insulin analogue,
Insulin lispro
(Humalog)6
Lasker S et al. J Diabet 2010; 1: 1-8.
Greene J et al. N Engl J Med 2015; 372(12): 1171–1175
DeVries J et al. Diabetes, Obesity and Metabolism 2015; 17: 445–451.
Humulin Prescribing Information. February
Humalog Prescribing Information. March 2015.

5. 1922 2000 1923 2004 1963 Insulin molecule isolated
Sanofi-Aventis: insulin glargine (Lantus®) analogue7
Lilly: first insulin for human use
Synthetic insulin produced
Novo Nordisk: insulin detemir (Levemir®) analogue8
Hilgenfeld R et al. Drugs 2014; 74(8): 911–927.
EMA Assessment Report: Levemir (insulin detemir) Available at: Accessed: April 2015.

6. Novo Nordisk: insulin degludec
2013
2014
2015
Novo Nordisk: insulin degludec
(Tresiba®)9
Insulin degludec for diabetes mellitus. Drug Ther Bull 2013; 51(7):78–81.

7. 2013 2014 2015 Lilly: first approved biosimilar Insulin (Abasaglar®)10
and first rapid acting insulin (Humalog)
200 units/ml 6,11
Humalog Prescribing Information. March 2015.
Abasaglar Prescribing Information. May 2015.
EMA Humalog 200 authorisation Available at: /human/000088/WC pdf. Accessed April 2015.

8. insulin glargine U-300 (Toujeo®)12
2013
2014
2015
Sanofi:
insulin glargine U-300 (Toujeo®)12
EMA assessment report: Toujeo (insulin glargine) Available at: Accessed: June 2015.

9. Biosimilar medicines versus traditional medicines
• Large molecules derived from microorganisms, human or animal cells
• Made up of proteins, sugars and nucleic acids
• Biosimilars are similar copies of a reference
biologic
Traditional medicines
• Simpler, smaller structures
• Chemically synthesised
• Copies are called generics
European Commission Information Document. Accessible from Last accessed February 2015.

10. A biosimilar medicine must demonstrate1 Biosimilars
Biosimilar medicines
A biosimilar medicine must demonstrate1
Biosimilars
• Similar active ingredient2
• Similar in vitro and in vivo non-clinical characteristics2
• Similar PK and PD1
• Similar efficacy2
• Similar safety2
• Not generics3
• Potential for cost saving4
• Around since 2006; 19 now approved5
• Set to change the EU diabetes marketplace6
EMEA Guideline Accessible from: Last accessed April 2015.
EMEA Guideline 2014 CHMP/437/04. Accessible from:
Declerck P GaBI J 2012; 1: 13–6.
EuropaBio Guide to Biological Medicines, Focus on Biosimilar Medicines Accessible from: Last accessed April 2015.
GaBi Accessible from Last accessed April 2015.
DeVries J et al. Diab Obes Metab 2015; 17: 445 – 451.

11. Abasaglar® development programme
“The totality of evidence”
Phase 3
studies1-3
• Identical amino acid sequence to Lantus® insulin glargine
• Highly similar to Lantus® based on principles of biosimilarity including bioequivalence criteria
• Comprehensive development program to demonstrate similarity at high standards
Element 1
T1DM
Element 2
T2DM
Phase 1 studies4-6
PK / PD of Abasaglar® versus Lantus®
Preclinical studies
Biochemical and physicochemical characterisation
Blevins TC, Dahl D, Rosenstock J et al. 2015
Rosenstock J et al. Diabetes Obes Metab 2015; doi: /dom [Epub ahead of print].
Deeg Met al. ADA 2014: 70-OR.
Linnebjerg Het al. ADA 2014: 889-P.
Zhang et al. X ADA 2014: 890-P.
Heise T et al. ADA 2014: 891-P.
PD=pharmacodynamic;
PK=pharmacokinetic; T1DM=type 1 diabetes mellitus;
T2DM=type 2 diabetes mellitus Data from BI & Lilly alliance

12. Abasaglar®: phase 1 data
Pharmacokinetics
Pharmacodynamics
Duration of action
Dosing
Abasaglar®: phase 1 data

13. PK: serum insulin concentration profiles similar for Abasaglar® and Lantus®*1
Data from Linnebjerg H et al. ADA 2014: 889-P.
*Healthy subjects
Linnebjerg H et al. ADA 2014: 889-P.

14. PK: serum insulin concentration profiles similar for Abasaglar® and Lantus® at two dose levels1
Data from Zhang X et al. ADA 2014: 890-P.
Zhang X et al. ADA 2014: 890-P.

15. PD: mean glucose infusion rates similar between Abasaglar® and Lantus®
Data from Linnebjerg H et al. ADA 2014: 889-P.
*Healthy subjects
Linnebjerg H et al. ADA 2014: 889-P.

16. Duration of action: survival curves for Abasaglar® and Lantus® were similar1 (log rank test of equality, p=0.859)
Data from Heise T et al. ADA 2014: 891-P.
• Cox proportional hazard estimate (Abasaglar®/Lantus®) duration of action was 1.063; p=
• Results demonstrate similar duration of action Abasaglar®/Lantus®1
Heise T et al. ADA 2014: 891-P.

17. Phase 1: conclusions
Abasaglar® insulin glargine demonstrates highly similar pharmacokinetic and pharmacodynamic properties to Lantus® insulin glargine
Linnebjerg H et al. American Diabetes Association 74th Scientific Sessions, San Francisco, CA, June 13-17, 2014: 889-P.
Heise T et al. American Diabetes Association 74th Scientific Session, San Francisco, CA, June 13-17, 2014: 891-P.
Zhang X et al. American Diabetes Association 74th Scientific Sessions, San Francisco, CA, June 13-17, 2014: 890-P.

18. Any questions?

19. Part 2: ELEMENT 2 study
Phase 3 clinical study comparing efficacy and safety of Abasaglar® insulin glargine to Lantus® insulin glargine in type 2 diabetes

20. ELEMENT 21:
EFFICACY AND SAFETY WITH ABASAGLAR® INSULIN GLARGINE COMPARED WITH LANTUS® INSULIN GLARGINE IN PATIENTS WITH T2DM
HbA1c
Immunogenicity
Hypoglycaemia
Primary endpoint
To demonstrate the non-inferiority of Abasaglar® insulin glargine to Lantus® insulin glargine as measured by change in HbA1c from baseline to 24 weeks, when used in combination with OADs
Rosenstock J et al. Diabetes Obes Metab 2015; doi: /dom [Epub ahead of print].

21. ELEMENT 2: Study design Data from Rosenstock J et al. 2015.
a3 patients (Abasaglar®) discontinued before receiving study drug.
IGlar=insulin glargine; BMI=body mass index; FBG=fasting blood glucose; HbA1c=glycosylated hemoglobin; OAD=oral antidiabetic drug; QD=once daily;  SC=subcutaneous; T2DM; type 2 diabetes mellitus.

22. ELEMENT 2: baseline demographics and patient characteristics
Data from Rosenstock J et al and Supplement to: Rosenstock J et al
Data are mean ± standard deviation unless otherwise indicated.
aFull analysis set, n numbers reflect maximum sample size for all demographics / characteristics with the exception of FBG. bBy SMBG. *p=<0.05.
P>0.05 for all treatment comparisons except where indicated. BMI=body mass index; FBG=fasting blood glucose; HbA1c=glycosylated hemoglobin; SMBG= self-monitored blood glucose.

23. ELEMENT 2: similar changes in HbA1c and similar % of patients reaching target HbA1c1
Data from Rosenstock J et al
HbA1c=glycosylated hemoglobin; NS=not significant.
Rosenstock J et al. Diabetes Obes Metab 2015; doi: /dom [Epub ahead of print].

24. ELEMENT 2: similar total, nocturnal and severe hypoglycaemia1
Data from Rosenstock J et al
Rosenstock J et al. Diabetes Obes Metab 2015; doi: /dom [Epub ahead of print].

25. ELEMENT 2: similar incidence of Treatment-Emergent Antibody Response (TEAR)1
Data from Rosenstock J et al. ADA 2014: 64-OR.
TEAR criteria
• If antibody was not detected at baseline
• If antibody was detected at baseline
% antibody binding ≥1.26%
absolute increase in % antibody binding of 1% and 30% relative increase from baseline
LOCF=last observation carried forward.
Rosenstock J et al. ADA 2014: 64-OR.

26. ELEMENT 2: negligible effect of overall TEAR status on change in clinical outcomes1
Data from Deeg M et al. ADA 2014: 70-OR.
Data are least squares mean (standard error) change from baseline to LOCF endpoint.
p >0.05 for all treatment-by-TEAR interactions.
HbA1c=glycosylated hemoglobin; LOCF=last observation carried forward; TEAR=treatment-emergent antibody response.
Deeg M et al. ADA 2014: 70-OR.

27. ELEMENT 2 summary1,2
Abasaglar® insulin glargine compared with Lantus® insulin glargine demonstrated similar:
Adverse-event profile
Incidence of treatment-emergent antibody response
Glucose-lowering effect (FBG, SMBG, HbA1c)
Changes in body weight
Hypoglycaemia incidence and rates
Allergic and injection site reactions
Insulin
doses
Rosenstock J et al. Diabetes Obes Metab 2015; doi: /dom [Epub ahead of print].
Deeg M et al. ADA 2014: 70-OR.

28. ELEMENT 2 summary1,2
In patients with T2DM, Abasaglar® insulin glargine compared with Lantus® insulin glargine, in combination with oral antidiabetic drugs, provided equivalent efficacy and similar safety profiles, with no clinically meaningful differences.
Rosenstock J et al. Diabetes Obes Metab 2015; doi: /dom [Epub ahead of print].
Deeg M et al. ADA 2014: 70-OR.

29. Any questions?

30. Part 3: ELEMENT 1 study
Phase 3 clinical study comparing efficacy and safety of Abasaglar® insulin glargine to Lantus® insulin glargine in type 1 diabetes

31. ELEMENT 1:
EFFICACY AND SAFETY WITH ABASAGLAR® INSULIN GLARGINE COMPARED WITH LANTUS® INSULIN GLARGINE IN PATIENTS WITH T1DM
HbA1c
Immunogenicity
Hypoglycaemia
Primary endpoint
To demonstrate non-inferiority of Abasaglar® insulin glargine to Lantus® insulin glargine as measured by change in HbA1c from baseline to 24 weeks in T1DM

32. ELEMENT 1: Study design Data from Blevins T et al. ADA 2014: 69-OR.
a1 patient (Abasaglar®) discontinued before receiving study drug.
IGlar=insulin glargine; BMI=body mass index; HbA1c=glycosylated hemoglobin; NPH=Neutral Protamine Hagedorn; QD=once daily; SC=subcutaneous; T1DM; type 1 diabetes mellitus; TID=thrice daily.

33. ELEMENT 1: Baseline patient characteristics
Data from Blevins T et al. ADA 2014: 69-OR.
Data are mean ± standard deviation unless otherwise indicated.
aFull analysis set, n numbers reflect maximum sample size.
BMI=body mass index; FBG=fasting blood glucose; HbA1c=glycosylated hemoglobin; SMBG=self-monitored blood glucose.

34. ELEMENT 1: similar HbA1c changes from baseline and over time1
Data from Blevins T et al. ADA 2014: 69-OR.
*p=0.03; no significant differences between treatments at any other time point.
Blevins T et al. ADA 2014: 69-OR.

35. ELEMENT 1: similar total, nocturnal and severe hypoglycaemia1
Data from Blevins T et al. ADA 2014: 69-OR.
All p-values >0.05.
Blevins T et al. ADA 2014: 69-OR.

36. ELEMENT 1: similar Treatment-Emergent Antibody Response (TEAR)1
Data from Deeg M et al. ADA 2014: 70-OR.
TEAR criteria
• If antibody was not detected at baseline
• If antibody was detected at baseline
% antibody binding ≥1.26%
absolute increase in % antibody binding of 1% and 30% relative increase from baseline
Deeg M et al. ADA 2014: 70-OR.

37. ELEMENT 1: negligible effect of overall TEAR status on change in clinical outcomes1
Data from Deeg M et al. ADA 2014: 70-OR.
Data are least squares mean (standard error) change from baseline to LOCF endpoint.
p >0.05 for all treatment-by-TEAR interactions.
HbA1c=glycosylated hemoglobin; LOCF=last observation carried forward; TEAR=Treatment-Emergent Antibody Response. .
Deeg M et al. ADA 2014: 70-OR.

38. ELEMENT 1 summary1,2
At 24 and 52 weeks, in patients with T1DM, Abasaglar® insulin glargine compared to Lantus® insulin glargine demonstrated similar:
Insulin doses (basal, prandial, total)
Incidence of treatment-emergent antibody response
Glucose-lowering effect (HbA1c, FBG, mean BG)
Changes in body weight
Hypoglycaemia incidence and rates
Allergic and injection site reactions
Adverse-event profile
Blevins T et al. ADA 2014: 69-OR.
Deeg M et al. ADA 2014: 70-OR.

39. ELEMENT 1 summary1,2
Abasaglar® insulin glargine provided an equivalent efficacy and a similar safety profile compared to Lantus® insulin glargine, with no clinically meaningful differences
Blevins T et al. ADA 2014: 69-OR.
Deeg M et al. ADA 2014: 70-OR.

40. Any questions?

41. Where does Abasaglar® fit in the 2015 insulin landscape?
Consider the basal insulin landscape for type 1 and 2 diabetes:
Ultimately, the right insulin regimen for patients with diabetes is the one tailored to their needs.1 Insulin analogues can bring flexibility and convenience to diabetes management.1
• NPH
• Concentrated insulin
• Insulin glargines, insulin degludec, etc.
Barnett A et al. Int J Clin Pract 2008; 62(11): 1647‒1653.

42. Abasaglar® Abbreviated prescribing information

43. Humulin® and Humalog® Abbreviated prescribing information

44. Humulin® and Humalog® Abbreviated prescribing information