Lilly Diabetes: Pipeline Update

Transcription

1 Lilly Diabetes: Pipeline Update June 16, 2014

2 Safe Harbor Provision This presentation contains forward-looking statements that are based on management's current expectations, but actual results may differ materially due to various factors. The company's results may be affected by factors including, but not limited to, the risks and uncertainties in pharmaceutical research and development; competitive developments; regulatory actions; litigation and investigations; business development transactions; economic conditions; and changes in laws and regulations, including health care reform. For additional information about the factors that affect the company s business, please see the company s latest Forms 10-K and 10-Q filed with the Securities and Exchange Commission. The company undertakes no duty to update forward-looking statements. Lilly Diabetes 2

3 Lilly Diabetes: An Overview Enrique Conterno President, Lilly Diabetes

4 Lilly Diabetes Pipeline The following assets are part of the Lilly-Boehringer Ingelheim collaboration: Trajenta, Jardiance, New Insulin Glargine Product. *The safety and efficacy of the agents under investigation has not been established. There is no guarantee that the agents will receive regulatory approval and become commercially available for the uses being investigated. **Approved in the EU and in Australia. Lilly Diabetes 4

5 Recent Events Dec Feb March 2014 April 2014 May 2014 FDA accepted NDA filing for LY insulin glargine Positive topline data for dulaglutide (AWARD-6) FDA issued CRLs for empagliflozin and Humalog U200 Jardiance approved in Australia, marking first international approval FDA accepted NDA filing for empagliflozin/ linagliptin fixed-dose combination EMA granted marketing authorization for Jardiance Positive topline Phase III results for basal insulin peglispro Q4 Q1 Q2 Lilly Diabetes 5

6 Dulaglutide Jessie Fahrbach, M.D. Medical Director, Lilly Diabetes *The safety and efficacy of dulaglutide has not been established. There is no guarantee that dulaglutide will receive regulatory approval and become commercially available for the uses being investigated.

7 Dulaglutide Agenda Dulaglutide Presentation Agenda Dulaglutide Overview AWARD-2: Dulaglutide versus Insulin Glargine AWARD-4: Dulaglutide + Mealtime Insulin Lispro versus Insulin Glargine + Mealtime Insulin Lispro AWARD-6: Dulaglutide versus Liraglutide GBDZ: Single-Use Pen Summary and Next Steps Lilly Diabetes 7

8 Dulaglutide Overview Dulaglutide Presentation Agenda Dulaglutide Overview AWARD-2: Dulaglutide versus Insulin Glargine AWARD-4: Dulaglutide + Mealtime Insulin Lispro versus Insulin Glargine + Mealtime Insulin Lispro AWARD-6: Dulaglutide versus Liraglutide GBDZ: Single-Use Pen Summary and Next Steps Lilly Diabetes 8

9 Dulaglutide Overview Dulaglutide A recombinant GLP-1 Fc fusion protein linking a human GLP-1 peptide analog and a variant of a human IgG4 Fc fragment 1,2 Extended plasma half-life (~5 days) Minimal renal clearance Low immunogenic potential Once weekly dosing Solution injection: no reconstitution needed GLP-1 analog Linker Modified IgG4 Fc domain 1. Glaesner et al. Diabetes Metab Res Rev 2010;26(4): Nauck et al. Diabetes Care 2014;(Ahead of print) Lilly Diabetes 9

10 Dulaglutide Overview Dulaglutide Clinical Overview Completed Trial AWARD-1 (combination with met + pio) AWARD-2 (combination with met + SU) AWARD-3 (monotherapy) AWARD-4 (combination with insulin lispro +/- met) AWARD-5 (combination with met) Change in HbA1c at Primary Endpoint Active Comparator 0.75mg 1.5mg Exenatide BID Superior Superior Insulin Glargine Non-inferior Superior Metformin Superior Superior Insulin Glargine Superior Superior Sitagliptin Superior Superior AWARD-6 (combination with met) AWARD: Assessment of Weekly AdministRation of LY in Diabetes Liraglutide 1.8 mg Not studied Non-inferior Ongoing: REWIND: Event-driven (~9,800 patients) study to assess CV risk Phase 3b studies: AWARD-7 (H2H glargine in patients with CKD), AWARD-8 (Add-on SU), AWARD-9 (Add-on basal) = presented today Lilly Diabetes 10

11 Dulaglutide AWARD-2 Dulaglutide Presentation Agenda Dulaglutide Overview AWARD-2: Dulaglutide versus Insulin Glargine AWARD-4: Dulaglutide + Mealtime Insulin Lispro versus Insulin Glargine + Mealtime Insulin Lispro AWARD-6: Dulaglutide versus Liraglutide GBDZ: Single-Use Pen Summary and Next Steps Lilly Diabetes 11

12 Dulaglutide AWARD-2 Study Design Key inclusion criteria T2D not optimally controlled on 1, 2, or 3 OAMs A1C 7% and 11% at screening A1C >6.5% at pre-randomization visit Background Therapy a Dulaglutide 1.5 mg Dulaglutide 0.75 mg Insulin Glargine titrated to target b Safety Follow-up Screening & Lead-in Treatment Period Follow-up Week Randomization Primary Time Point Final Time Point Abstract 330-OR, 74 th American Diabetes Association (ADA) a During the lead-in period, metformin ( 1500 mg) and glimepiride ( 4 mg) were titrated up to maximum tolerated dose, then doses were stable for 6 to 8 weeks. OAMs continued for the duration of the trial. b Fasting plasma glucose target: <100 mg/dl. Kennedy et al. (2006) GOAL A1C Trial Lilly Diabetes 12

13 Baseline Patient Characteristics Baseline Characteristics Similar Dulaglutide AWARD-2 Characteristics DU 1.5 mg N = 273 DU 0.75 mg N = 272 Glargine N = 262 Sex, F (%) Age, years 56 (10) 57 (9) 57 (9) Duration of diabetes, years 9 (6) 9 (6) 9 (6) BMI, kg/m 2 31 (5) 32 (5) 32 (6) A1C, % 8.2 (1) 8.1 (1) 8.1 (1) Fasting serum glucose, mg/dl 165 (49) 161 (49) 163 (48) Treatment at screening, % 1 OAM OAMs At Randomization Metformin dose (mg/day) 2379 (480) 2412 (495) 2419 (475) Glimepiride dose (mg/day) 6.3 (1.7) 6.3 (1.6) 6.2 (1.6) Abstract 330-OR, 74 th American Diabetes Association (ADA) Values shown are for mean (SD) unless otherwise noted, ITT Lilly Diabetes 13

14 A1C Change from Baseline at 52 Weeks Dulaglutide 1.5 mg Superior to Insulin Glargine Dulaglutide AWARD-2 Baseline A1C = 8.1% A1C, Change from Baseline (%) * DU 1.5 mg DU 0.75 mg Glargine (-0.60, -0.29) a Abstract 330-OR, 74 th American Diabetes Association (ADA) Data presented are LS means ± SE p <0.001, superiority vs glargine (1-sided, adjusted to control for Type I error) *p <0.001, noninferiority vs glargine a Treatment difference (nominal 95% CI), ITT, ANCOVA Lilly Diabetes 14

15 Weight Change from Baseline Over Time Significant, Sustained Weight Loss with Dulaglutide Dulaglutide AWARD-2 Baseline Weight = 86.3 kg DU 1.5 mg Body Weight, Change from Baseline (kg) DU 0.75 mg Glargine Weight Difference 3.4 kg Abstract 330-OR, 74 th American Diabetes Association (ADA) Time (Weeks) Data presented are LS means ± SE p <0.001 vs glargine ITT, MMRM analysis Lilly Diabetes 15

16 Rates of Hypoglycemia at 52 Weeks Dulaglutide 1.5 mg Associated with Lower Hypoglycemia Dulaglutide AWARD-2 DU 1.5 mg DU 0.75 mg Events/Patient/Year # Total 7.9 # Documented Symptomatic Glargine 0.7 Nocturnal 2.1 Abstract 330-OR, 74 th American Diabetes Association (ADA) # p <0.05 vs glargine; p <0.001 vs glargine ITT, Negative Binomial regression analysis, 70 mg/dl threshold Lilly Diabetes 16

17 Adverse Events at 78 Weeks Most Commonly Reported AEs for Dulaglutide were GI-related Dulaglutide AWARD-2 DU 1.5 mg N = 273 DU 0.75 mg N = 272 Glargine N = 262 Any adverse event, n (%) 201 (73.6) 188 (69.1) 192 (73.3) Gastrointestinal adverse event, n (%) Nausea 42 (15.4) 21 (7.7) 4 (1.5) Diarrhea 29 (10.6) 25 (9.2) 15 (5.7) Vomiting 18 (6.6) # 10 (3.7) 3 (1.1) Severe hypoglycemia, n (%) 2 (0.7) 0 (0.0) 2 (0.8) Injection site reactions, n (%) 2 (0.7) 2 (0.7) 0 (0.0) Adjudicated Pancreatitis, n (%) 2 (0.7) 1 (0.4) 0 (0.0) Pancreatic cancer, n Abstract 330-OR, 74 th American Diabetes Association (ADA) # p <0.05 vs glargine; p <0.001 vs glargine Lilly Diabetes 17

18 Dulaglutide AWARD-2 Summary and Conclusions Efficacy Compared to glargine: Dulaglutide 1.5 mg resulted in significantly greater improvement in A1C, with weight loss and less hypoglycemia Dulaglutide 0.75 mg resulted in similar improvement in A1C, with weight loss and less hypoglycemia Safety and Tolerability Dulaglutide had higher rates of gastrointestinal-related adverse events than glargine Safety profile similar to GLP-1 receptor agonist class Abstract 330-OR, 74 th American Diabetes Association (ADA) Lilly Diabetes 18

19 Dulaglutide AWARD-4 Dulaglutide Presentation Agenda Dulaglutide Overview AWARD-2: Dulaglutide versus Insulin Glargine AWARD-4: Dulaglutide + Mealtime Insulin Lispro versus Insulin Glargine + Mealtime Insulin Lispro AWARD-6: Dulaglutide versus Liraglutide GBDZ: Single-Use Pen Summary and Next Steps Lilly Diabetes 19

20 Dulaglutide AWARD-4 Study Design Key inclusion criteria 1 or 2 insulin doses/ day (basal, basal with prandial, or premixed insulin) ± OAMs Insulin dose stable for 3 months A1C 7.0% and 11.0% Body mass index 23 and 45 kg/m 2 Key exclusion criteria Type 1 diabetes Signs, symptoms, and/or history of pancreatitis, severe cardiovascular, hepatic, or kidney disease Glomerular filtration rate 30 ml/min/1.73 m 2 Background Therapy* Dulaglutide 1.5 mg + Prandial Insulin Lispro Dulaglutide 0.75 mg + Prandial Insulin Lispro Insulin Glargine + Prandial Insulin Lispro Safety Follow-up Screening & Treatment Period Follow-up Lead-in Week Randomization Primary Time Point Final Time Point Abstract 979-P, 74 th American Diabetes Association (ADA) *Patients continued conventional insulin therapy ± metformin Note: Metformin was the only OAM allowed after screening; minimum required dose was 1500 mg/day by Week -7 and stable thereafter. During the 52-week treatment period, patients followed treat-to-target insulin lispro and insulin glargine dosing algorithms 1,2 Lilly Diabetes 20

21 Baseline Patient Characteristics Baseline Characteristics Similar Dulaglutide AWARD-4 Characteristics DU 1.5 mg N = 295 DU 0.75 mg N = 293 Glargine N = 296 Sex, F (%) Age, years 59 (10) 59 (9) 60 (9) Race, white (%) A1C, % 8.5 (1) 8.4 (1) 8.5 (1) Weight, kg 91 (18) 92 (18) 91 (19) Duration of diabetes, years 13 (7) 12 (7) 13 (7) Fasting serum glucose, mg/dl 157 (54) 150 (50) 154 (56) Abstract 979-P, 74 th American Diabetes Association (ADA) Values shown are for mean (SD) unless otherwise noted Lilly Diabetes 21

22 A1C Change from Baseline at 26 Weeks Both Dulaglutide Doses Superior to Insulin Glargine Dulaglutide AWARD-4 Baseline A1C = 8.5% A1C, Change from Baseline (%) DU 1.5 mg DU 0.75 mg Glargine (-0.33, -0.02) a (-0.38, -0.07) a Abstract 979-P, 74 th American Diabetes Association (ADA) p <0.025 superiority vs glargine Data presented are LS means ± SE a Treatment difference (nominal 95% CI), ITT, ANCOVA LOCF analysis Lilly Diabetes 22

23 Weight Change Over Time Dulaglutide Demonstrated Relative Weight Benefit Baseline Weight = 91.1 kg Baseline Weight = 91.1 kg Dulaglutide AWARD-4 DU 1.5 mg DU 0.75 mg Glargine Body Weight, Change from Baseline (kg) Time (Weeks) Abstract 979-P, 74 th American Diabetes Association (ADA) p <0.001 vs glargine Data presented are LS means ± SE ITT, MMRM analysis Lilly Diabetes 23

24 Rates of Hypoglycemia at 26 Weeks Dulaglutide 1.5 mg Associated With Less Hypoglycemia Dulaglutide AWARD-4 Baseline Weight = 91.1 kg 63.2 DU 1.5 mg DU 0.75 mg Events/Patient/Year # Glargine Total Documented Symptomatic Nocturnal Severe Abstract 979-P, 74 th American Diabetes Association (ADA) # p <0.05 vs glargine; p <0.001 vs glargine Lilly Diabetes 24

25 Adverse Events at Week 52 Most Commonly Reported AEs for Dulaglutide were GI-related Dulaglutide AWARD-4 DU 1.5 mg N = 295 DU 0.75 mg N = 293 Glargine N = 296 Any adverse event, n (%) 217 (73.6) 230 (78.5) 206 (69.6) Gastrointestinal adverse events, n (%) Nausea 76 (25.8) 52 (17.7) 10 (3.4) Vomiting 49 (16.6) 46 (15.7) 18 (6.1) Diarrhea 36 (12.2) 31 (10.6) 5 (1.7) Injection site reactions, n (%) 1 (0.3) 4 (1.4) 0 Adjudicated Pancreatitis, n Pancreatic cancer, n Abstract 979-P, 74 th American Diabetes Association (ADA) p <0.001 vs glargine Lilly Diabetes 25

26 Dulaglutide AWARD-4 Summary and Conclusions Efficacy When combined with insulin lispro, once-weekly dulaglutide 1.5 mg and dulaglutide 0.75 mg were superior to glargine, as measured by the reduction in A1C levels at 26 and 52 weeks Dulaglutide was associated with statistically significantly less weight gain than glargine Safety and Tolerability Dulaglutide had higher rates of gastrointestinal-related adverse events compared to glargine Hypoglycemia risk was lower with dulaglutide 1.5 mg and similar with dulaglutide 0.75 mg as compared to glargine Abstract 979-P, 74 th American Diabetes Association (ADA) Lilly Diabetes 26

27 Dulaglutide Presentation Agenda Dulaglutide AWARD-6 Dulaglutide Overview AWARD-2: Dulaglutide versus Insulin Glargine AWARD-4: Dulaglutide + Mealtime Insulin Lispro versus Insulin Glargine + Mealtime Insulin Lispro AWARD-6: Dulaglutide versus Liraglutide GBDZ: Single-Use Pen Summary and Next Steps Lilly Diabetes 27

28 Dulaglutide AWARD-6 Study Design Key inclusion criteria Type 2 diabetes Metformin monotherapy 1500 mg/day A1C 7.0% and 10.0% Key exclusion criteria Type 1 diabetes History of pancreatitis Elevated serum calcitonin 20 pg/ml Background Therapy Screening & Lead-in Dulaglutide 1.5 mg once weekly + metformin* Liraglutide 1.8 mg once daily + metformin* Treatment Period Safety Follow-up Followup Week Randomization Final Time Point Liraglutide titration period a Abstract 110-LB, 74 th American Diabetes Association (ADA) *Patients received metformin 1500 mg/day throughout the study a Patients randomized to liraglutide were initiated at a dose of 0.6 mg/day. After Week 1, patients were up-titrated to 1.2 mg/day and then at Week 2, to 1.8 mg/day Patients who could not tolerate the full dose for the treatment duration were required to discontinue study drug. Rescue therapy initiated for prespecified thresholds for severe, persistent hyperglycemia Lilly Diabetes 28

29 Baseline Patient Characteristics Similar Baseline Characteristics Dulaglutide AWARD-6 Characteristics DU 1.5 mg N = 299 LIRA 1.8 mg N = 300 Sex, F (%) Age, years 56 (9) 57 (10) Weight, kg 94 (18) 94 (19) BMI, kg/m 2 34 (5) 34 (5) A1C, % 8.1 (0.8) 8.1 (0.8) Duration of diabetes, years 7 (5) 7 (5) Fasting serum glucose, mg/dl 167 (39) 165 (42) Mean metformin dose, mg 2012 (418) 2068 (452) Abstract 110-LB, 74 th American Diabetes Association (ADA) Values shown are for mean (SD) unless otherwise noted Lilly Diabetes 29

30 A1C Results at 26 Weeks Dulaglutide 1.5 mg Similar to Liraglutide 1.8 mg Dulaglutide AWARD-6 A1C Change from Baseline Baseline A1C = 8.1% Forest Plot Chart NI Margin A1C, Change from Baseline (%) DU 1.5 mg LIRA 1.8 mg Favors Dulaglutide Favors Liraglutide (-0.19, 0.07) a p<0.001, noninferiority vs liraglutide Abstract 110-LB, 74 th American Diabetes Association (ADA) Data presented are LS means ± SE a Treatment difference (nominal 95% CI), ITT, MMRM Lilly Diabetes 30

31 Percent to Goal at 26 Weeks Dulaglutide 1.5 mg Similar to Liraglutide 1.8 mg Dulaglutide AWARD-6 A1C <7.0% A1C 6.5% Patients (%) DU 1.5 mg LIRA 1.8 mg DU 1.5 mg LIRA 1.8 mg Abstract 110-LB, 74 th American Diabetes Association (ADA) ITT, Logistic Regression using LOCF analysis Lilly Diabetes 31

32 Weight Change from Baseline at 26 Weeks Both Treatments Led to Significant Weight Loss from Baseline Dulaglutide AWARD-6 Baseline Weight = 94 kg DU 1.5 mg LIRA 1.8 mg Body Weight, Change from Baseline (kg) # (0.28) a -3.6 Abstract 110-LB, 74 th American Diabetes Association (ADA) # p = 0.01 vs liraglutide Data presented are LS means ± SE ITT, Logistic Regression using LOCF analysis a LS means ± SE Lilly Diabetes 32

33 Adverse Events through 26 Weeks Adverse Events Similar with Both Treatments Dulaglutide AWARD-6 DU 1.5 mg N = 299 LIRA 1.8 mg N = 300 Any AE, n (%) 185 (61.9) 189 (63.0) Gastrointestinal AE, n (%) 107 (35.8) 107 (35.7) Nausea 61 (20.4) 54 (18.0) Vomiting 21 (7.0) 25 (8.3) Diarrhea 36 (12.0) 36 (12.0) Dyspepsia 24 (8.0) 18 (6.0) Study/Study Drug Discontinuations for Gastrointestinal AE 9 (3.0) 13 (4.3) Injection site reactions, n (%) 1 (0.3) 2 (0.7) Hypoglycemia ( 70 mg/dl ± symptoms) Total (events/pt/year), mean (SD) 0.34 (1.44) 0.52 (3.01) Adjudicated Pancreatitis, n 0 0 Pancreatic cancer, n 0 0 Abstract 110-LB, 74 th American Diabetes Association (ADA) Lilly Diabetes 33

34 Dulaglutide AWARD-6 Summary and Conclusions Efficacy Once weekly dulaglutide 1.5 mg demonstrated non-inferior glycemic control compared to once daily liraglutide 1.8 mg Both dulaglutide and liraglutide had robust A1C reductions with the majority of patients reaching ADA A1C target of <7.0% Both treatment groups demonstrated weight loss; liraglutide had statistically greater weight loss (0.7 kg) than dulaglutide Safety and Tolerability Dulaglutide and liraglutide had a similar safety and tolerability profile Abstract 110-LB, 74 th American Diabetes Association (ADA) Lilly Diabetes 34

35 Dulaglutide GBDZ Dulaglutide Presentation Agenda Dulaglutide Overview AWARD-2: Dulaglutide versus Insulin Glargine AWARD-4: Dulaglutide + Mealtime Insulin Lispro versus Insulin Glargine + Mealtime Insulin Lispro AWARD-6: Dulaglutide versus Liraglutide GBDZ: Single-Use Pen Summary and Next Steps Lilly Diabetes 35

36 Dulaglutide GBDZ Single-Use Pen (SUP) Ready to use solution (no reconstitution) Hidden, small needle already attached Similar in size to marketed diabetes pens Steps for use: uncap, place and unlock, inject Provides dose confirmation Injection process <5 seconds Automatically retracts needle following injection Abstract 122-LB, 74 th American Diabetes Association (ADA) Lilly Diabetes 36

37 Dulaglutide GBDZ Study Design Key inclusion criteria T2D, naïve to self-injection and injecting others, BMI: 23 and 45 kg/m 2 Screening Study Period I Study Period II Once-weekly SUP placebo injection 1 Week 3 Weeks Visit Week T1 1 T D-FISQ pre-assessment Training Initial injection at site Patient completes Diary and Pain Module Home Injections Patient completes Diary and Pain Module Telephone visits Final Injection at site Patient completes diary and MDDAB Modules: Pain (0-10 scale) Ease of use Experience Features Modified D-FISQ post-assessment Abstract 122-LB, 74 th American Diabetes Association (ADA) Phase 3b, multicenter, open-label, single-arm, outpatient study Patients used SUP to self-inject 0.5 ml of placebo subcutaneously once-weekly; the initial and final injections were observed to evaluate injection success or failure Lilly Diabetes 37

38 Dulaglutide GBDZ Summary and Conclusions Injection success rate Primary objective met - final injection success rate 99.1% Secondary objective met - initial injection success rate 97.2% Patient perceptions using Single-Use Pen Pain scores across injections were low (mean 1.2 at initial injection, mean 0.8 at final injection, on scale of 0 to 10), suggesting little or no pain There was a significant reduction from baseline in the fear of self-injecting score (from mean 3.7 at initial injection to mean 1.0 at final injection) 99% of patients found the Single-Use Pen easy/very easy to use A positive injection experience may be an important factor for some patients and providers when initiating injectable therapy Abstract 122-LB, 74 th American Diabetes Association (ADA) Lilly Diabetes 38

39 Dulaglutide Summary Dulaglutide Presentation Agenda Dulaglutide Overview AWARD-2: Dulaglutide versus Insulin Glargine AWARD-4: Dulaglutide + Mealtime Insulin Lispro versus Insulin Glargine + Mealtime Insulin Lispro AWARD-6: Dulaglutide versus Liraglutide GBDZ: Single-Use Pen Summary and Next Steps Lilly Diabetes 39

40 Dulaglutide Summary Summary and Next Steps Summary Across six Phase III clinical trials, dulaglutide demonstrated significant, sustained efficacy, with a safety and tolerability profile that is similar to the class If approved, dulaglutide would be the only GLP-1 receptor agonist that is both once-weekly and ready to use, and it could be an important new treatment option for type 2 diabetes Next Steps Dulaglutide is under regulatory review in the United States, EU and several other countries If approved, dulaglutide will be marketed under the brand name Trulicity Lilly Diabetes 40

41 Questions and Answers