Investor science event from ADA 2010 Orlando, 28 June 2010
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Introduction Dr. Karl Mahler, Head of Investor Relations
Investor science events at major medical meetings At least five events will highlight Roche s leadership Date / location 6 June 2010 Chicago, USA 28 June 2010 Orlando, USA 26 July 2010 Anaheim, USA October 2010 Milan, Italy October 2010 Gothenburg, Sweden Meeting ASCO (American Society of Clinical Oncology) ADA (American Diabetes Association) AACC (American Association for Clinical Chemistry) ESMO (European Society for Medical Oncology) ECTRIMS (European Committee for Treatment and Research in Multiple Sclerosis) Key assets / newsflow Avastin, MabThera/Rituxan, RG3502(T-DM1), RG1273(pertuzumab), etc. Franchise update CardioMetabolism, RG1583(taspoglutide), etc. Diagnostics review & update Avastin, RG3502(T-DM1), etc. RG1594(ocrelizumab) Steady flow of important clinical data & results 4
Taspoglutide & the GLP-1 class: Product attributes along three distinct dimensions Taspoglutide: Potential for best-in-class convenience Convenience (Injection frequency (BID, QD or QW), need for corrections, simple injection vs reconstitution, needle gauge) Taspoglutide: Robust, consistent efficacy Taspoglutide: Work ongoing to refine profile All GLP-1s have specific safety / tolerability challenges Efficacy (HbA1c, % pts reaching <7.0, FBG, weight loss, persistence of efficacy, increased insulin secretion, beta cell function) Safety / Tolerability (Hypoglycemia, nausea, vomiting, diarrhea, hypersensitivity, pancreatitis, thyroid cancer) 5
Investor science event from ADA 2010 Programme 28 June 2010 6.30-8.00 pm Introduction Dr. Karl Mahler, Head of Investor Relations Franchise overview: CardioMetabolism Dr. Fouzia Laghrissi Thode, Global Product Strategy Head for Metabolism and Anemia Taspoglutide: Overview of data at ADA 2010 Dr. Bruce Cooper, Head of Global Medical Affairs Taspoglutide: T-emerge 5 - comparison w/insulin glargine Prof. Dr. med. Michael Nauck Taspoglutide: Next steps Dr. Bruce Cooper, Head of Global Medical Affairs Questions & Answers Moderator: Dr. Karl Mahler Expected duration up to 1½ hour Dinner reception 6
Franchise overview: CardioMetabolism Dr. Fouzia Laghrissi Thode, Global Product Strategy Head for Metabolism and Anemia
Recent announcement Risk mitigation plan implemented To date, out of approximately 3,000 taspoglutide-treated patients in the phase III programme, a total of 23 cases of serious hypersensitivity reactions have been reported as related to taspoglutide by investigators (i.e. incidence < 1%) Roche has identified a potential association between anti-drug antibodies (ADAs) and an increased risk for patients to experience serious hypersensitivity reactions ADA levels will be routinely monitored and patients that develop pre-specified ADA levels will discontinue treatment and continue to be monitored in the trial 8
Serious hypersensitivity reactions Hypersensitivity reactions judged by investigators as serious Anaphylaxis or other systemic allergic reactions (ie, urticaria, angioedema) Anaphylaxis symptoms included: Cutaneous reactions (skin and/or mucosa): e.g., urticaria, angioedema Gastrointestinal: e.g., prolonged nausea and/or vomiting Respiratory: e.g., dyspnea Cardiovascular: e.g., blood pressure and/or heart rate changes No anaphylactic shock All patients recovered without complications Only one patient hospitalized overnight for observation Some patients were treated with antihistamines, steroids and one case was treated with adrenaline
Our commitment to CardioMetabolism Development T-emerge most comprehensive program in diabetes to date Dalcetrapib largest patient trial undertaken by Roche Pharma Aleglitazar initiating in 24 countries CardioMetabolism franchise Building capabilities Establishing leadership in CardioMetabolism Research gred and pred programs Active partnering Preparing for mid and long-term success in new disease area 10
Value for patients Taspoglutide Glycemic control Minimizing hypoglycemia Reducing weight Aleglitazar Unique profile to reduce CV risk in Type 2 diabetes Dalcetrapib Improved CV outcomes by treating the underlying disease of atherosclerosis 11
Development programs to deliver first or best in class dal-heart Raising HDL through CETP modulation to reduce cardiovascular risk ALECARDIO CV risk reduction for patients with type 2 diabetes post-acs dal-outcomes 15,600 patients dal-vessel 450 patients dal-plaque ALECARDIO 6,000 patients ALENEPHRO 300 patients 130 patients dal-plaque2 900 patients 12
RG1658(dalcetrapib) dal-outcomes phase III study now fully recruited Target population by risk status 1 Phase III dal-outcomes 15,600 CHD 2 pts w/recent ACS 3 Best standard of care +/- dalcetrapib 600 mg qd Event-driven trial First patient in Q2-08, last patient in Q2-10 Expected interim efficacy analysis in Q3-11 (event-driven), expected regulatory filing in 2013 Targeted indication: Prevention of cardiovascular event in very high risk patients Primary outcomes study supported by secondary phase II/III studies; dal-vessel, dal-plaque, dal-plaque2 1 Roche epidemiology prevalence projection based on National Center for Health Statistics NHANES data (2009) 2 CHD=Coronary heart disease 3 ACS=Acute coronary syndrome 13
RG1439(aleglitazar) ALECARDIO phase III study enrolling Target population growing fast 1 Phase III ALECARDIO in 24 countries 6,000 T2D 2 pts hospitalized w/acs 3 Best standard of care +/- aleglitazar 150 μg qd Event-driven trial First patient in Q1-10; enrollment on track Regulatory filing expected in 2014 Targeted indication: Prevention of cardiovascular event in Type 2 diabetes patients post ACS 1 Patients with T2D 2 and ACS 3 (excl CHF NYHA II-IV) 2 T2D=Type 2 diabetes 3 ACS=Acute Coronary Syndrome 14
Taspoglutide: Overview of data at ADA 2010 Dr. Bruce Cooper, Head of Global Medical Affairs
Phase 3 Program: Over 6000 Patients, >1000 sites, 50 Countries Study Name Patient Population Sample Size Taspoglutide Comparator T-emerge 1 T-emerge 2 T-emerge 3 T-emerge 4 T-emerge 5 T-emerge 6 T-emerge 7 T-emerge 8 Inadequately controlled on diet & exercise Inadequately controlled with Met, TZD, or Met + TZD Inadequately controlled with pioglitazone + Met Inadequately controlled with Met Inadequately controlled on Met + SU; SU withdrawn at pre-randomization Inadequately controlled with SU Met Inadequately controlled with Met (high BMI) Patients with higher cardiovascular risk 373 1189 326 666 1049 760 10 mg QW 20 mg QW* 10 mg QW 20 mg QW* 10 mg QW 20 mg QW* 10 mg QW 20 mg QW* 10 mg QW 20 mg QW* 10 mg QW 20 mg QW* Placebo Exenatide BID Placebo Sitagliptin Placebo Insulin glargine Pioglitazone 305 20 mg QW* Placebo 2000 20 mg QW* Placebo BID = twice daily; BMI = body mass index; Met = metformin; QW = once weekly; SU = sulfonylurea; TZD = thiazolidinedione. *10 mg taspoglutide QW for 4 weeks followed by 20 mg QW. 16
Taspoglutide in T2DM: Headline Results from ADA Study Description Headline Results/status H2H vs. exenatide Primary endpoint met: Superior HbA1c reduction versus twice-daily exenatide Early Disease Vs. placebo, monotherapy Primary endpoint met: Superior HbA1c reduction versus placebo Treatment Naïve H2H vs. sitagliptin vs. placebo Primary endpoint met: Superior HbA1c reduction versus sitagliptin Early Disease H2H vs. insulin glargine Primary endpoint met: Non-inferior HbA1c reduction versus insulin glargine Advanced Disease Vs. placebo, obese T2D patients Primary endpoint met: Superior HbA1c reduction versus placebo Early Disease T-emerge Included Treatment Naïve T2D Patients With Early & Advanced Disease 17
Study Design for the Active-Controlled Studies: T-emerge 2, 4, 5, and 6 Taspoglutide formulation Once-weekly SC injection 29-g needle Prefilled syringe Primary Endpoint Patient screening 10 mg* Taspoglutide 10 mg QW Taspoglutide 20 mg QW Taspoglutide 10 mg QW Taspoglutide 20 mg QW Follow-up 2-year long-term extension Active comparator Active comparator 4 4* 2 24 weeks 28-week extension 0 weeks Week 24 52 weeks *Patients randomized to taspoglutide 20 mg QW will receive taspoglutide 10 mg QW for 4 weeks followed by the 20 mg QW dosing. Active comparator: TE-2, exenatide; TE-4, sitagliptin; TE-5, insulin glargine; TE-6, pioglitazone. TE-4: sitagliptin active comparator and also includes placebo-controlled group. 18
Study Design for the Placebo-Controlled Studies: T-emerge 1, 3, and 7 Taspoglutide formulation Once-weekly SC injection 29-g needle Prefilled syringe Primary Endpoint Patient screening 10 mg* Placebo Taspoglutide 10 mg QW Taspoglutide 20 mg QW 10 mg* Taspoglutide 10 mg QW Taspoglutide 20 mg QW Taspoglutide 10 mg QW Taspoglutide 20 mg QW Follow-up 4 4* 2 24 weeks 28-week extension 0 weeks Week 24 52 weeks *Patients randomized to taspoglutide 20 mg QW receive taspoglutide 10 mg QW for 4 weeks followed by the 20 mg QW dosing. TE-1: 3-week patient screening and 2-week placebo run-in. TE-7 trial does not include taspoglutide 10 mg QW dose group. 19
Overall Baseline Demographics and Disease Characteristics Mean (SD) unless specified TE-1 (N=354) TE-2 (N=1149) TE-4 (N=636) TE-5 (N=1028) TE-7 (N=292) Men n (%) 130 (37) 608 (53) 352 (55) 549 (53) 119 (41) Age, y 55 (10) 56 (10) 56 (10) 58 (9) 54 (10) Weight, kg 86.8 (18.0) 94.4 (19.2) 92.4 (19.3) 90.8 (19.5) 102.5 (18.1) BMI, kg/m 2 32.3 (5.1) 33.4 (5.2) 32.5 (5.1) 32.4 (5.3) 36.7 (4.9) HbA1c, % 7.60 (1.01 8.07 (0.91) 7.96 (0.87) 8.28 (0.90) 7.55 (0.84) HbA1c baseline 8.0% n (%) 108 (31) 572 (50) 281 (44) 610 (59) 83 (28) FPG, mg/dl 158 (45) 178 (46) 173 (46) 201 (52) 130 (37) Diabetes duration, y 2.4 (2.5) 6.6 (5.4) 5.9 (4.7) 9.1 (6.0) 5.1 (4.2) History of CV disorders* n (%) 55 (15) 183 (16) 99 (15) 198 (19) 49 (16) Intent-to-treat population. *Patients in the safety population with 1 cardiovascular disorder. 20
Primary Endpoint: HbA1c Change From Baseline After 24 Weeks of Treatment Placebo Taspoglutide 10 mg QW Taspoglutide 20 mg QW Active comparator TE-1 Monotherapy TE-2 Metformin, TZD, or both TE-4 Metformin TE-5 Metformin, SU withdrawal TE-7 Metformin Baseline (%) 7.6 7.5 7.7 8.1 8.1 8.1 8.0 8.0 8.0 7.9 8.2 8.3 8.3 7.5 7.5 Exenatide Sitagliptin Insulin glargine * * * * * LOCF = last-observation-carried-forward; LSMean = least square mean; SE = standard error. *P<0.001 vs placebo; P<0.001 vs active comparator. Intent-to-treat population; LOCF analysis. TE-5: Sulfonylurea treatment withdrawn prior to randomization for all patients. 21
Time Course Example: TE-1 HbA1c Change From Baseline Over 24 Weeks of Treatment Placebo (n=115) Taspoglutide 10 mg QW (n=112) Taspoglutide 20 mg QW (n=127) * * LSMean = least square mean; SE = standard error. *P<0.001 vs placebo. Intent-to-treat population; last-observation-carried-forward analysis. 22
Percentage of Patients Reaching Target HbA1c <7% After 24 Weeks of Treatment Placebo Taspoglutide 10 mg QW Taspoglutide 20 mg QW Active comparator TE-1* Monotherapy TE-2 Metformin, TZD, or both TE-4 Metformin TE-5 Metformin, SU withdrawal TE-7* Metformin Exenatide Sitagliptin Glargine *Baseline entry criterion for TE-1 and TE-7 trial was HbA1c 6.5%; this analysis excluded patients from TE-1 and TE-7 with baseline HbA1c <7%. 23
Fasting Plasma Glucose (mg/dl) Change From Baseline After 24 Weeks of Treatment Placebo Taspoglutide 10 mg QW Taspoglutide 20 mg QW Active comparator TE-1 Monotherapy TE-2 Metformin, TZD, or both TE-4 Metformin TE-5 Metformin, SU withdrawal TE-7 Metformin Baseline (mg/dl) 156 158 162 179 177 178 174 176 174 169 190 190 203 158 163 * * Exenatide * * Sitagliptin Insulin glargine * LSMean = least square mean; SE = standard error; Intent-to-treat population; LOCF analysis *P<0.001 vs placebo; P<0.01 vs active comparator; P< 0.001 vs active comparator. TE-5: Sulfonylurea treatment withdrawn prior to randomization of all patients. Insulin dose titrated to FPG target. 24
Time Course Example: TE-1 Fasting Plasma Glucose Over 24 Weeks of Treatment Placebo (n=115) Taspoglutide 10 mg QW (n=112) Taspoglutide 20 mg QW (n=127) FPG (mg/dl) (Mean SE) * * *P<0.001 vs placebo. Intent-to-treat population; last-observation-carried-forward analysis.
Body Weight Change From Baseline After 24 Weeks of Treatment Placebo Taspoglutide 10 mg QW Taspoglutide 20 mg QW Active comparator TE-1 Monotherapy TE-2 Metformin, TZD, or both TE-4 Metformin TE-5 Metformin, SU withdrawal TE-7 Metformin Baseline (kg) 87 88 85 95 93 95 91 94 92 93 90 91 91 101 104 Exenatide Sita Glar * Glar = insulin glargine; LSMean = least square mean; SE = standard error; Sita = sitagliptin; TZD = thiazolidinedione. *P<0.05 vs placebo; P<0.05 vs active comparator; P<0.01 vs placebo; P<0.001 vs placebo or vs active comparator. Intent-to-treat population; last-observation-carried-forward analysis. 26
Time-Course of Body Weight Change From Baseline Over 24 Weeks of Treatment Placebo Taspoglutide 10 mg QW Taspoglutide 20 mg QW Active comparator TE-1 TE-2 TE-4 TE-5 TE-7 Change in body weight (kg) from baseline (LSMean SE) * Exenatide Sitagliptin Insulin glargine Diet & exercise LSMean = least square mean; SE = standard error. *P<0.05 vs placebo; P<0.05 vs active comparator; P<0.01 vs placebo; P<0.001 vs placebo or vs active comparator. Intent-to-treat population; last-observation-carried-forward analysis. 27
Body Weight Loss Responder Rates After 24 Weeks of Treatment: 5% Placebo Taspoglutide 10 mg QW Taspoglutide 20 mg QW Active comparator TE-1 Monotherapy TE-2 Metformin, TZD, or both TE-4 Metformin TE-5 Metformin TE-7 Metformin Exenatide Sita Glar Glar = insulin glargine; Sita = sitagliptin; TZD = thiazolidinedione. Intent-to-treat population; last-observation-carried-forward analysis. 28
Safety Overview at 24 Weeks Incidence of nausea: 26-47% Incidence of vomiting: 17-28% Injection site reactions generally mild to moderate and infrequently lead to discontinuation (1.4-5%) % withdrawals due to all adverse events 10mg: 9-17% 20mg: 21-28% Control: 7-16% % withdrawals due to nausea or vomiting (T-emerge 2; H2H vs. exenatide) 10mg: 4.1% 20mg: 7.6% Exenatide: 6.5% 29
Example: TE-2 Number of Episodes of Nausea or Vomiting Over 24 Weeks Taspoglutide 10 mg QW Taspoglutide 20 mg QW Exenatide 10 g BID Nausea Vomiting % of patients # of Episodes # of Episodes Safety population. Withdrawals due to nausea or vomiting: exenatide: 6.5%, taspoglutide 10 mg QW: 4.1%, taspoglutide 20 mg QW: 7.6% 30
Example: TE-2 Weekly Incidence of Nausea and Vomiting Over 24 Weeks Taspoglutide 10 mg QW Taspoglutide 20 mg QW Exenatide 10 g BID Up-titration from 10 mg to 20 mg Nausea Up-titration from 10 mg to 20 mg Vomiting Safety population 86% and 83% of vomiting occurred on Day of Injection for taspoglutide 10 mg QW and 20 mg QW, respectively 31
Summary T-emerge program studied taspoglutide across a wide spectrum of patient types (including treatment-naive and patients with early disease and advanced disease) and versus 4 active comparators (exenatide, sitagliptin, pioglitazone, and even the highest dose of insulin glargine used in a GLP-1 registration study) In the T-emerge Clinical Development Program, taspoglutide demonstrated evidence of consistent glycemic control with low risk of hypoglycemia and significant weight loss in a ready-to-use weekly injection As has been seen with other GLP-1 receptor agonists, the most frequently reported adverse events with taspoglutide were related to gastrointestinal tolerability * Based on T-emerge results to-date at 24 weeks 32
Taspoglutide: T-emerge 5 - comparison w/insulin glargine Prof. Dr. med. Michael Nauck
T-emerge 5 Taspoglutide, a Once-Weekly Human GLP-1 Analog, Provides Comparable Glycemic Control to Insulin Glargine, with Superior Weight Loss and Less Hypoglycemia in Type 2 Diabetes: A Phase 3, Open-Label Trial (T-emerge 5) Michael Nauck, 1 Edward Horton, 2 Mirjana Andjelkovic, 3 Javier Ampudia-Blasco, 4 Mark N. Boldrin, 5 Raffaella Balena 3 1 Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany 2 Joslin Diabetes Center, Boston, MA, United States 3 F.Hoffmann-La Roche, Basel, Switzerland 4 Clinic University Hospital, Valencia, Spain 5 Roche Pharmaceuticals, Nutley, NJ, United States 34
Taspoglutide, a Once-Weekly Human GLP-1 Analog Phase 3 Program: Over 6000 Patients Study Name Patient Population Sample Size Taspoglutide Comparator T-emerge 1 T-emerge 2 T-emerge 3 T-emerge 4 T-emerge 5 T-emerge 6 T-emerge 7 T-emerge 8 Inadequately controlled on diet & exercise Inadequately controlled with Met, TZD, or Met + TZD Inadequately controlled with pioglitazone + Met Inadequately controlled with Met Inadequately controlled on Met + SU; SU withdrawn pre-randomization Inadequately controlled with SU Met Inadequately controlled with Met (high BMI) Patients with higher cardiovascular risk 373 1189 326 666 1049 760 10 mg QW 20 mg QW* 10 mg QW 20 mg QW* 10 mg QW 20 mg QW* 10 mg QW 20 mg QW* 10 mg QW 20 mg QW* 10 mg QW 20 mg QW* Placebo Exenatide BID Placebo Sitagliptin Placebo Insulin glargine Pioglitazone 305 20 mg QW* Placebo 2000 20 mg QW* Placebo BID = twice daily; BMI = body mass index; Met = metformin; QW = once weekly; SU = sulfonylurea; TZD = thiazolidinedione. *10 mg taspoglutide QW for 4 weeks followed by 20 mg QW. 35
Objectives of Study Primary objective To demonstrate non-inferiority of taspoglutide to insulin glargine on glycemic control (HbA 1c ) after 24 weeks of treatment in insulin-naive type 2 diabetic patients inadequately controlled with metformin and sulphonylurea combination therapy Secondary objectives To assess the effects of taspoglutide on additional parameters of glycemic control, body weight, and cardiovascular risk factors after 24 weeks To assess the safety and the tolerability of taspoglutide after 24 and 52 weeks 36
Study Design: Randomized, Open-label, Parallel Group, Active-Controlled Study population HbA 1c 7.0% and 10.0% Stable doses for 12 weeks of metformin ( 1500 mg/day or individual maximally tolerated dose) and sulfonylurea (any dose) BMI 25 (> 23 for Asians) and 45 kg/m 2 Stable weight 5 % for at least 12 weeks Primary Endpoint Patient screening 10 mg Taspoglutide 10 mg QW Taspoglutide 20 mg QW Insulin glargine* Taspoglutide 10 mg QW Taspoglutide 20 mg QW Insulin glargine Follow up Long-term extension up to 3 years Sulfonylurea treatment stopped 5 days prior to start of study 4 4* 24 weeks 28-week extension 0 weeks Week 24 52 weeks *Forced titration scheme to target FPG 110 mg/dl (6.1 mmol/l) Patients will receive taspoglutide 10 mg QW for 4 weeks followed by the 20 mg QW dosing 37
Baseline Demographic Characteristics (N=1028) Mean (SD) unless specified Taspoglutide 10 mg QW (n=361) Taspoglutide 20 mg QW (n=348) Insulin glargine (n=319) Age, years 58 (10) 57 (9) 58 (9) BMI, kg/m 2 32.1 (5.3) 32.4 (5.3) 32.7 (5.2) HbA 1c, % 8.2 (0.9) 8.3 (0.9) 8.3 (0.9) HbA 1c baseline > 8.0%, n (%) 208 (58) 206 (59) 196 (61) FPG, mg/dl 200 (54) 199 (52) 202 (51) Diabetes duration, years 9 (6) 9 (6) 9 (6) Intent-to-treat population. 38
Primary Endpoint: HbA 1c Over 24 Weeks of Treatment Taspoglutide 10 mg QW (n = 361) *Final mean daily insulin glargine dose = 36 IU Taspoglutide 20 mg QW (n = 348) Insulin glargine* (n = 319) Non-inferiority margin Taspoglutide 20 mg vs insulin glargine -0.14-0.28-0.01-0.77-0.84-0.98 Taspoglutide 10 mg vs insulin glargine 0.07-0.06 0.21-0.5-0.4-0.3-0.2-0.1 0 0.1 0.2 0.3 0.4 Treatment difference for HbA 1c (%, 95% CI) LSMean = least square mean; SE = standard error. Intent-to-treat population; last-observation-carried-forward analysis. 39 Non-inferiority/Superiority Summary of HbA1c Change from Baseline at Week 24 (LOCF, ITT)
Percentage of Patients Reaching Target HbA 1c After 24 Weeks of Treatment Taspoglutide 10 mg QW Taspoglutide 20 mg QW Insulin glargine* HbA 1c < 7.0% HbA 1c 6.5% n= 361 348 319 361 348 319 Intent-to-treat population; last-observation-carried-forward analysis. * Final mean daily insulin glargine dose = 36 IU. 40
Change in FPG and insulin titration Taspoglutide 10 mg (baseline=190 mg/dl) Taspoglutide 20 mg (baseline=190 mg/dl) Insulin glargine (baseline=203 mg/dl) - 0.0 60 Daily Dose of Insulin Glargine (IU) Change in FPG (mg/dl) from baseline (LSMean SE) - - * * - - -1.0-2.0-3.0-4.0 mmol/l Insulin Dose (IU/day) (LSMean SD) 50 40 30 20 10 0 10 19 27 30 0 4 8 12 16 20 24 35 36 Time (weeks) *P < 0.001 vs insulin glargine. Intent-to-treat population; LOCF analysis. Forced titration scheme to target FPG 110 mg/dl (6.1 mmol/l) 41
Two-hour Postprandial Glucose (PPG) (mg/dl): Corrected for Fasting Glucose at Baseline and Week 24* Taspoglutide 10 mg QW (n=31) Taspoglutide 20 mg QW (n=36) Insulin glargine (n=35) Baseline Week 24-14.7-27.5-1.9 2-Hour post-meal glucose (mg/dl) (mean SD) -12.4-26.3 1.5 6.4-5.6 18.5-30 -25-20 -15-10 -5 0 5 10 15 20 *Subset of patients Glucose level at 2-hr post-meal minus fasting glucose at 0 hr Change from baseline for PPG (mg/dl; mean [95% CI]) 42
Change in Body Weight Over 24 Weeks of Treatment Taspoglutide 10 mg QW (n=361) Taspoglutide 20 mg QW (n=348) Insulin glargine (n=319) Baseline (kg) 90.2 91.5 90.6 Change in body weight (kg) from baseline (LSMean SE) * * * * *P < 0.001 vs insulin glargine. Intent-to-treat population; last-observation-carried-forward analysis. Final mean daily insulin glargine dose = 36 IU. 43
Safety Overview During the 24 Week Treatment Period Taspoglutide 10 mg N=364 n (%) Taspoglutide 20 mg N=351 n (%) Insulin glargine N=322 n (%) Total pts with > 1 AE 285 (78.3) 301 (85.8) 187 (58.1) Serious AEs 14 (3.8) 16 (4.6) 11 (3.4) AEs leading to discontinuation 41 (11.3) 61 (17.4) 7 (2.2) Deaths 1 (0.3) 1 2 (0.6) 1 Hypoglycemia* Reported 18 (4.9) 21 (6.0) 56 (17.4) Confirmed (< 55 mg/dl) 1 (0.3) 3 (0.9) 10 (3.1) Severe *Reported: symptoms without or without confirmation by measured plasma glucose concentration. Confirmed: symptoms accompanied by measured plasma glucose concentration 55 mg/dl. Severe: requiring assistance to actively administer carbohydrate, glucagon, or other resuscitative actions. p < 0.001 vs. insulin glargine 1 Non-drug related 44 Safety population.
Summary of Adverse Events With 5 % Incidence Rate Taspoglutide 10 mg N=364 n (%) Taspoglutide 20 mg N=351 n (%) Insulin glargine N=322 n (%) Gastrointestinal disorders Nausea 143 (39.3) 159 (45.3) 6 (1.9) Vomiting 72 (19.8) 80 (22.8) 4 (1.2) Diarrhea 48 (13.2) 46 (13.1) 18 (5.6) General disorders and administration site conditions Injection site nodule 39 (10.7) 55 (15.7) - Injection site pruritus 26 (7.1) 17 (4.8) 1 (0.3) Metabolism and nutrition disorders Hypoglycemia 18 (4.9) 21 (6.0) 56 (17.4) Decreased appetite 30 (8.2) 35 (10.0) 2 (0.6) Infections and infestations Nasopharyngitis 20 (5.5) 20 (5.7) 25 (7.8) Nervous system disorders Headache 25 (6.9) 30 (8.5) 16 (5.0) Dizziness 19 (5.2) 16 (4.6) 7 (2.2) Safety population 45
Summary of Patients Withdrawn, by Reason Taspoglutide 10 mg N=364 n (%) Taspoglutide 20 mg N=351 n (%) Insulin glargine N=322 n (%) Withdrawals for any reason 76 (20.9) 74 (21.1) 29 (9.0) Adverse event * 32 (8.8) 47 (13.4) 3 (0.9) Nausea 9 (2.5) 19 (5.4) Vomiting 7 (1.9) 9 (2.6) Diarrhea 2 (0.5) 2 (0.6) Injection site reaction 2 (0.5) 2 (0.6) Fatigue 2 (0.6) Hypersensitivity 1 (0.3) 3 (0.9) Hyperglycemia 9 (2.5) 6 (1.7) 3 (0.9) Withdrew consent 15 (4.1) 14 (4.0) 8 (2.5) Failure to return 3 (0.8) 1 (0.3) 7 (2.2) Insufficient therapeutic response 18 (4.9) 8 (2.3) 4 (1.2) Refused treatment did not cooperate 4 (1.1) 2 (0.6) 4 (1.2) Administrative/other 2 (0.5) - 2 (0.6) Violation of selection criteria at entry 2 (0.5) 1 (0.3) - Death - 1 (0.3) 1 (0.3) Safety population * For individual adverse events, only those occurring 0.5% in any group are reported. 46
Number of Episodes of Nausea or Vomiting Over 24 Weeks Taspoglutide 10 mg (n = 364) Taspoglutide 20 mg (n = 351) Insulin glargine (n = 322) Nausea Vomiting % of patients # of Episodes # of Episodes Safety population. Withdrawals due to nausea or vomiting: taspoglutide 10 mg: 4% taspoglutide 20 mg: 7% insulin glargine: 0% 47
Weekly Incidence of Nausea and Vomiting Over 24 Weeks Taspoglutide 10 mg Taspoglutide 20 mg Insulin glargine Up-titration from 10 mg to 20 mg Nausea Up-titration from 10 mg to 20 mg Vomiting Safety population 81 % and 84 % of vomiting occurred on day of injection for taspoglutide 10 mg and 20 mg, respectively. 48
Summary Taspoglutide demonstrated non-inferior HbA 1c lowering (- 0.98 % vs. - 0.84 %) and better HbA 1c goal achievement of < 6.5% (24 % vs. 14 %) vs. well titrated insulin glargine (mean dose = 36 IU/d) Incidence of reported hypoglycemia was 4.9-6.0% for taspoglutide vs. 17.4 % for insulin glargine Taspoglutide demonstrated significant weight loss of - 4.1 kg (vs. - 0.4 kg for insulin glargine) Most frequently reported adverse events for taspoglutide were gastrointestinal in nature Among patients reporting nausea or vomiting, there was predominantly a single episode that infrequently led to discontinuation and tended to occur early in treatment on the day of injection Conclusions As with other GLP-1 receptor agonists, the most common adverse events with taspoglutide are related to GI tolerability In patients with inadequate glycemic control on metformin and sulfonylurea, replacing a sulfonylurea with taspoglutide demonstrated comparable HbA 1c lowering and target HbA 1c control with a low risk of hypoglycemia and weight loss as compared to insulin glargine 49
Taspoglutide: Next steps Dr. Bruce Cooper, Head of Global Medical Affairs
Taspoglutide: The situation today Our challenge Filing delayed a minimum of 12 to 18 months Higher than expected incidence of serious hypersensitivity (<1%) Gastrointestinal tolerability profile Our response Risk mitigation plan to protect the safety of patients in the phase III programme Investigating root cause and assessing potential solutions to address hypersensitivity reactions Further studies to optimise the gastrointestinal profile Ongoing analysis of 52 weeks data from the overall T-emerge programme 51
What we know: Efficacy Combined benefits of robust A1c reduction, with low risk of hypoglycemia and clinically important weight loss in a simple ready-to-use weekly injection Consistent results across all studies and across a wide spectrum of Type 2 diabetes patients Statistically superior A1c reduction vs exenatide BID, sitagliptin and metformin getting up to 71% of patients to ADA HbA1c treatment goal Superior combined benefit to a well-titrated dose of insulin glargine (36IU) with significantly more patients reaching target HbA1c with less hypoglycemia and superior weight loss Both 10mg and 20mg doses are effective 20mg has higher weight loss 52
What we know: Safety & tolerability The type of adverse events reported are in line with the GLP-1 class Nausea and vomiting were higher than the targeted product profile, however, in general these events were mild to moderate, occurred early in the treatment course, usually on the day of injection and predominantly as a single episode Serious hypersensitivity reactions occurred late in the program and is being investigated and addressed with a risk mitigation plan Cross-study comparisons with other GLP-1s are valid only in well-conducted head to head trials 53
The path forward - I CV safety study T-emerge 8 continues to recruit Patients who develop anti-drug antibody levels above a pre-specified limit will be withdrawn from a study and continue to be followed up Hypersensitivity investigations Additional assessments of affected patients Additional antibody assessments including profile of other GLP-1 s Search for any factors that can be addressed Continued commitment to patient safety and transparency with decisions based on consultation with scientific, clinical and regulatory experts, and data analysis 54
The path forward - II Studies planned to optimise gastrointestinal tolerability E.g. dose timing, associated meal, site of injection Extension studies continue - data from T-emerge 2 at 52 weeks show: HbA1c superiority for both doses vs. exenatide Overall incidence of gastrointestinal adverse events and the incidence of adverse events leading to withdrawal were higher in each taspoglutide arm Analysis of the data ongoing Additional 52 weeks data from T-emerge trials are expected soon and will help us better inform the safety, tolerability and efficacy profile of taspoglutide Continued commitment to patient safety and transparency with decisions based on consultation with scientific, clinical and regulatory experts, and data analysis 55
Questions & Answers Moderator: Dr. Karl Mahler
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