Post on 18-Jun-2020
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American Diabetes Association 76th Scientific Sessions
Investor and analyst event
New Orleans, 13 June 2016
Shanghai – part of Cities Changing Diabetes
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Forward-looking statements
Novo Nordisk’s reports filed with or furnished to the US Securities and Exchange Commission (SEC), including the company’s Annual Report 2015 and Form 20-F, which are both filed with the SEC in February 2016 in continuation of the publication of the Annual Report 2015, and presentations made, written information released, or oral statements made, to the public in the future by or on behalf of Novo Nordisk, may contain forward-looking statements. Words such as ‘believe’, ‘expect’, ‘may’, ‘will’, ‘plan’, ‘strategy’, ‘prospect’, ‘foresee’, ‘estimate’, ‘project’, ‘anticipate’, ‘can’, ‘intend’, ‘target’ and other words and terms of similar meaning in connection with any discussion of future operating or financial performance identify forward-looking statements. Examples of such forward-looking statements include, but are not limited to:
• Statements of targets, plans, objectives or goals for future operations, including those related to Novo Nordisk’s products, product research, product development, product introductions and product approvals as well as cooperation in relation thereto
• Statements containing projections of or targets for revenues, costs, income (or loss), earnings per share, capital expenditures, dividends, capital structure, net financials and other financial measures
• Statements regarding future economic performance, future actions and outcome of contingencies such as legal proceedings, and
• Statements regarding the assumptions underlying or relating to such statements.
These statements are based on current plans, estimates and projections. By their very nature, forward-looking statements involve inherent risks and uncertainties, both general and specific. Novo Nordisk cautions that a number of important factors, including those described in this presentation, could cause actual results to differ materially from those contemplated in any forward-looking statements.
Factors that may affect future results include, but are not limited to, global as well as local political and economic conditions, including interest rate and currency exchange rate fluctuations, delay or failure of projects related to research and/or development, unplanned loss of patents, interruptions of supplies and production, product recall, unexpected contract breaches or terminations, government-mandated or market-driven price decreases for Novo Nordisk’s products, introduction of competing products, reliance on information technology, Novo Nordisk’s ability to successfully market current and new products, exposure to product liability and legal proceedings and investigations, changes in governmental laws and related interpretation thereof, including on reimbursement, intellectual property protection and regulatory controls on testing, approval, manufacturing and marketing, perceived or actual failure to adhere to ethical marketing practices, investments in and divestitures of domestic and foreign companies, unexpected growth in costs and expenses, failure to recruit and retain the right employees, and failure to maintain a culture of compliance.
Please also refer to the overview of risk factors in ‘Managing risks’ on p 42-43 of the Annual Report 2015.
Unless required by law, Novo Nordisk is under no duty and undertakes no obligation to update or revise any forward-looking statement after the distribution of this presentation, whether as a result of new information, future events or otherwise.
Important drug information
• Victoza® (liraglutide 1.2 mg & 1.8 mg) is approved for the management of type 2 diabetes only
• Saxenda® (liraglutide 3 mg) is approved in the US and EU for the treatment of obesity only
ADA 2016 investor and analyst event
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ADA 2016 investor and analyst event
Time Topic
6.15 pm Welcome - Early insights from Tresiba® launch in the US Jakob Riis, EVP China, Pacific and Marketing
6.20 pm SWITCH 1 and 2 - Reduced risk of hypoglycaemia with Tresiba® versus insulin glargine U100 demonstrated in the SWITCH trials Peter Kristensen, SVP Global Development
6.30 pm Faster-acting insulin aspart - Greater early glucose-lowering effect in type 1 diabetes demonstrated in clinical trials Peter Kurtzhals, SVP Global Research
6.40 pm LEADER - Statistically significant reduction in risk of major adverse cardiovascular events with Victoza® in the LEADER trial Mads Krogsgaard Thomsen, EVP and Chief Science Officer
6.55 pm SUSTAIN 2 and 3 - Superior HbA1c and weight reduction with once-weekly injectable semaglutide demonstrated in the SUSTAIN 2 and 3 trials and phase 2 results from oral semaglutide Alan Moses, SVP and Chief Medical Officer
7.05 pm Discussion and Q&A
Agenda
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0%
20%
40%
60%
80%
3/1/2013
0%
20%
40%
60%
80%
Continued steady growth in total number of Tresiba® prescriptions in the US
Steady Tresiba® growth trajectory in the US, while market share continues to grow in Japan despite biosimilar launch
Note: The graph does not show NPH, which accounts for the residual market share Source: IMS monthly data, May 2016
ADA 2016 investor and analyst event
Tresiba® continues to grow basal market share in Japan despite launch of biosimilar glargine
Levemir® NN total basal Tresiba®
glargine U100 glargine U300
Mar 2013
Apr 2016
62%
28% 26%
2%
Note: The graph does not show NPH, which accounts for the residual market share Source: IMS monthly data, April 2016 TRx: total prescription count; MS: market share
Basal Value MS
8%
Mar 2013
Mar 2016
biosimilar glargine
43% 43%
35%
8%
2%
6%
Levemir® NN total basal Tresiba®
glargine U100 glargine U300 Basal Value MS
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ADA 2016 investor and analyst event
SWITCH 1 and 2
Reduced risk of hypoglycaemia with Tresiba® versus insulin glargine U100
demonstrated in SWITCH trials
Peter Kristensen
SVP Global Development
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SWITCH 1 and 2 trial designs Baseline characteristics
SWITCH trials aimed to investigate the reduction of hypoglycaemia with Tresiba® versus insulin glargine U100
1 SWITCH 1: 20% dose reduction of basal and bolus insulin dose; 2 SWITCH 2: 20% dose reduction if coming from previous twice-daily treatment Note: Daily injections of both Tresiba® and insulin glargine evenly split between morning and evening IDeg: insulin degludec (Tresiba®) IGlar: insulin glargine U100; OAD: oral anti-diabetic; IAsp: insulin aspart
* In SWITCH 1, the pre-trial treatment regimen included 2-4 daily bolus insulin injections ** Does not add up to 100% as 19.4% were pump users prior trial enrollment and one patient could not be classified to a regimen BMI: body mass index; FPG: fasting plasma glucose Source: Lane et al., poster, 87-LB and Wysham et al., poster, 90-LB, ADA 2016
ADA 2016 investor and analyst event
IDeg once daily + 2-4 x IAsp 501 people
with type 1 diabetes
16 weeks titration
1,2
16 weeks HbA1c stable
16 weeks titration
1,2
16 weeks HbA1c stable
Randomised 1:1 Double-blinded
721 people with type 2 diabetes
SW
IT
CH
1
SW
IT
CH
2
IGlar once daily + 2-4 x IAsp
IGlar once daily + 2-4 x IAsp
IDeg once daily + 2-4 x IAsp
IDeg once daily ± OAD
IGlar once daily ± OAD
IGlar once daily ± OAD
IDeg once daily ± OAD
SWITCH 1 SWITCH 2
Mean age (years) 45.9 61.4
Mean diabetes duration (years)
23.4 14.1
Mean BMI (kg/m2) 27.5 32.2
Mean HbA1c 7.6% 7.6%
Mean FPG (mmol/L) 9.4 7.6
Basal once daily / Basal twice daily* 44.7% / 35.7%** 84.2% / 15.8%
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lower rate with
Tresiba®
Tresiba® showed lower rate of hypoglycaemia than insulin glargine U100 in maintenance period in the SWITCH 1 trial
ADA 2016 investor and analyst event
Severe events
Severe or BG confirmed symptomatic events
Severe or BG confirmed symptomatic nocturnal events
0
1
2
3
4
5
6
7
8
16 20 24 28 32
Cumulative events per patient
Weeks1
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
16 20 24 28 32
Weeks1
0.00
0.05
0.10
0.15
0.20
0.25
0.30
16 20 24 28 32
Tresiba® glargine U100
Weeks1
11%* 36%* 35%**
lower rate with
Tresiba®
lower rate with
Tresiba®
1 Since start of treatment period; BG: blood glucose; * (p<0.0001); ** (p<0.05) Source: Lane et al., poster, 87-LB, ADA 2016
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Tresiba® showed lower rate of hypoglycaemia than insulin glargine U100 in maintenance period in the SWITCH 2 trial
ADA 2016 investor and analyst event
Severe events
Severe or BG confirmed symptomatic events
Severe or BG confirmed symptomatic nocturnal events
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
16 20 24 28 32
Cumulative events per patient
0.00
0.05
0.10
0.15
0.20
0.25
0.30
16 20 24 28 32
0.000
0.005
0.010
0.015
0.020
0.025
0.030
16 20 24 28 32
Tresiba® glargine U100
Weeks1 Weeks1 Weeks1
30%* 42%* 46%**
Lower rate with
Tresiba®
Lower rate with
Tresiba®
Lower rate with
Tresiba®
1 Since start of treatment period; BG: blood glucose; * (p<0.0001); ** (p=0.2127) Source: Wysham et al., poster, 90-LB, ADA 2016
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SWITCH 1 – type 1 diabetes SWITCH 2 – type 2 diabetes
Lower hypoglycaemia risk with Tresiba® than with insulin glargine U100 in full treatment period in the SWITCH trials
BG: blood glucose; * (p<0.0001); ** (p<0.05); *** (p=0.2127); IGlar: insulin glargine Source: Lane et al., poster, 87-LB and Wysham et al., poster, 90-LB, ADA 2016
ADA 2016 investor and analyst event
0.94 [0.91;0.98]**
0.74 [0.61;0.91]**
0.75 [0.68;0.83]**
0.89 [0.85;0.94]*
0.64 [0.56;0.73]*
0.65 [0.48;0.89]**
0.25 0.5 1 2
Favours IGlar U100 Favours Tresiba®
0.25 0.5 1 2
0.77 [0.70;0.85]**
0.49 [0.26;0.94]**
Favours IGlar U100 Favours Tresiba®
0.75 [0.64;0.89]**
0.70 [0.61;0.80]*
0.58 [0.46;0.74]*
0.54 [0.21;1.42]***
Rate of severe or BG confirmed symptomatic hypoglycaemia
Rate of severe hypoglycaemia
Rate of severe or BG confirmed symptomatic nocturnal hypoglycaemia
Full treatment period Maintenance period
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ADA 2016 investor and analyst event
Faster-acting insulin aspart
Greater early glucose-lowering effect in type 1 diabetes demonstrated
in clinical trials
Peter Kurtzhals
SVP Global Research
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Twice as fast appearance in the bloodstream and twofold insulin exposure within first 30 min
More than 50% greater insulin action within the first 30 minutes
Pooled1 pharmacological analysis demonstrated faster onset of action with faster-acting insulin aspart in T1D
IAsp serum concentration (pmol/L)
n=261
0 30 60
0
50
100
150
200
250
300
9 4
n=256
GIR (mg/kg/min)
Minutes
8
0 30 60
0
2
4
6 n=163
n=160
1 Pooled analysis of PK/PD properties of faster aspart vs insulin aspart included 218 adult subjects with type 1 diabetes from 6 phase 1 randomized, double blind, crossover trials Note: Based on a 0.2 U/kg dose across all studies for both faster aspart and insulin aspart Source: Heise T et al., poster: 929-P, ADA 2016
faster aspart insulin aspart
Minutes
T1D: type 1 diabetes; faster aspart: faster-acting insulin aspart; IAsp: insulin aspart; GIR: glucose infusion rate; n: number randomised patients
faster aspart insulin aspart
ADA 2016 investor and analyst event
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Onset 1 trial design Baseline characteristics
Onset 1, a double-blind, treat-to-target trial investigating efficacy and safety of faster-acting insulin aspart in T1D
faster aspart: faster-acting insulin aspart; BMI: body mass index; FPG: fasting plasma glucose
Faster-acting insulin aspart (post meal)
Faster-acting insulin aspart (mealtime)
Insulin aspart (mealtime)
52
26
-8 0 Run-in
1,143 people with type 1 diabetes1
1 Inclusion criteria: Diagnosed with type 1 diabetes at least 12 months prior, age: 18 years or older, basal-bolus insulin treatment for at least 12 months and insulin detemir or insulin glargine treatment for at least 4 months prior to screening, HbA1C: 7.0-9.5%, BMI no higher than 35
Source: Russell-Jones et al., Oral 293-OR, ADA 2016
faster aspart
(mealtime)
insulin aspart
(mealtime)
faster aspart
(post meal)
Mean age (years)
46.1 43.7 43.5
Mean diabetes duration (years)
20.9 19.3 19.5
Mean BMI (kg/m2)
26.4 26.7 26.9
Mean HbA1c 7.6% 7.6% 7.6%
Mean FPG (mmol/L)
8.4 7.9 8.1
ADA 2016 investor and analyst event
Weeks
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Statistically significantly greater HbA1c reduction with faster aspart (mealtime) after 26 weeks
Lower PPG with faster-acting insulin aspart vs insulin aspart when administered at mealtime
Greater HbA1c and PPG reductions with faster aspart dosed at mealtime vs insulin aspart in the onset 1 trial
* p<0.0001 faster aspart: faster-acting insulin aspart; PPG: postprandial glucose Source: Russell-Jones et al., Oral 293-OR, ADA 2016
0.0
2.0
4.0
6.0
8.0
0 60 120 180 240
PPG increment (mmol/L)
*
**
* p<0.0001; ** p=0.0375
-0.32*
-0.13
-0.17
-0.7
-0.6
-0.5
-0.4
-0.3
-0.2
-0.1
0.0
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Weeks Minutes
ADA 2016 investor and analyst event
HbA1c reduction (%)
faster aspart (post meal)
faster aspart (mealtime)
insulin aspart (mealtime)
faster aspart (mealtime)
insulin aspart (mealtime)
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1 Treatment-emergent was defined as an event that has onset up to 1 day after last day of randomised treatment and excluding the events occurring in the run-in period. Estimated treatment ratios (faster aspart/standard insulin aspart) are presented with 95% confidence intervals BG: blood glucose; faster aspart: faster-acting insulin aspart
Similar rates of treatment-emergent1 hypoglycaemia across onset 1 treatment arms Safety conclusions
Faster-acting insulin aspart appeared to have a safety profile similar to that of insulin aspart in the onset 1 trial
Source: Russell-Jones et al., Oral 293-OR, ADA 2016
ADA 2016 investor and analyst event
0
5
10
15
20
25
30
0 4 8 12 16 20 24 28
Estimated ratio: 1.01 (0.88; 1.15)
Estimated ratio: 0.92 (0.81; 1.06)
Severe or BG- confirmed events per subject
• Overall, faster-acting insulin aspart appeared to have a safety profile similar to that of insulin aspart
• The overall rate of severe or blood glucose-confirmed hypoglycaemia was not statistically significantly different between faster aspart administered at mealtime, administered postmeal and standard insulin aspart administered at mealtime
• The overall adverse event rates were similar across the three treatment arms
• There was no difference in antibody development between the three treatment arms
Weeks
faster aspart (post meal)
faster aspart (mealtime)
insulin aspart (mealtime)
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ADA 2016 investor and analyst event
LEADER
Statistically significant reduction in risk of major adverse cardiovascular events
with Victoza® in the LEADER trial
Mads Krogsgaard Thomsen
EVP and chief science officer
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LEADER trial design Baseline characteristics
The LEADER trial was designed to investigate the CV profile of Victoza® versus placebo in addition to standard of care
BP: blood pressure * Heart failure includes New York Heart Association class I, II and III
ADA 2016 investor and analyst event
Standard of care + placebo (daily blinded injection)
Standard of care + Victoza®
(0.6-1.8 mg once daily)
0 3.5-5.0 years
9,340 patients with type 2 diabetes
Key inclusion criteria • Adults above 50 years with type 2 diabetes and
established cardiovascular disease, or above 60 years with multiple cardiovascular risk factors
• HbA1c 7.0% CV: cardiovascular Source: Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. 2016; In Press
Victoza® Placebo
Mean age (years) 64.2 64.4
Mean diabetes duration (years)
12.8 12.9
Mean BMI (kg/m2) 32.5 32.5
Mean HbA1c 8.7% 8.7%
Systolic BP (mmHg) 135.9 135.9
Diastolic BP (mmHg) 77.2 77.0
Heart failure* 17.9% 17.8%
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Victoza® statistically significantly reduced the risk of major adverse cardiovascular events in the LEADER trial
ADA 2016 investor and analyst event
13% reduction in 3-point MACE with Victoza® compared with placebo
MACE: major adverse cardiovascular events; 3-point MACE comprises cardiovascular death, non-fatal myocardial infarction and non-fatal stroke; CI: confidence interval Source: Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. 2016; In Press
Superiority of Victoza® vs placebo is consistent across sensitivity analyses
Patients with an event (%)
Months
Hazard ratio = 0.87 95% CI (0.78;0.97)
p<0.001 for non-inferiority p=0.011 for superiority
Victoza® Placebo • Non-inferiority of Victoza® vs placebo was confirmed for time to first MACE
• Superiority of Victoza® vs placebo was confirmed for time to first MACE
• Victoza® reduced the risk by 13% compared to placebo
• The result was consistent across sensitivity analyses
0
5
10
15
20
25
0 6 12 18 24 30 36 42 48 54
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2
4
6
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0 18 36 54
0
2
4
6
8
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0 18 36 54
0
2
4
6
8
10
0 18 36 54
All components of 3-point MACE contributed to the reduction in cardiovascular risk in the LEADER trial
ADA 2016 investor and analyst event
Non-fatal stroke Cardiovascular death Non-fatal
myocardial infarction
Months Months Months
Patients with an event (%)
HR = 0.78 95% CI (0.66;0.94)
p=0.007
Victoza® Placebo
HR = 0.88 95% CI (0.75;1.03)
p=0.11
HR = 0.89 95% CI (0.72;1.11)
p=0.30
HR: hazard ratio; CI: confidence interval Source: Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. 2016; In Press
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Victoza® also statistically significantly reduced the risk of expanded MACE in the LEADER trial
ADA 2016 investor and analyst event
12% reduction in expanded MACE with Victoza® compared with placebo
MACE: major adverse cardiovascular events; Expanded MACE includes cardiovascular death, non-fatal myocadial infarct, non-fatal stroke, coronary revascularization, or hospitalisation for unstable angina pectoris or hospitalisation for heart failure; CI: confidence interval Source: Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. 2016; In Press
Numerical reduction in selected secondary cardiovascular outcomes
* Per 100 patient years of observation 1 Not prespecified HR: hazard ratio
Hazard ratio = 0.88 95% CI (0.81;0.96)
p=0.005
Incidence rate* Victoza® Placebo HR
Transient ischemic attack1 0.3 0.3 0.79
Coronary revascularisation
2.3 2.5 0.91
Hospitalisation for unstable angina pectoris
0.7 0.7 0.98
Hospitalisation for heart failure 1.2 1.4 0.87
Months
Patients with an event (%)
Victoza® Placebo
0
5
10
15
20
25
0 6 12 18 24 30 36 42 48 54
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Statistically significant reduction in the rate of death from any cause
Numerical reduction in the proportion of patients hospitalised for heart failure
Reduced risk of all-cause-death and hospitalisation for heart failure with Victoza® vs placebo in the LEADER trial
HR: hazard ratio; CI: confidence interval Source: Source: Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. 2016; In Press and Buse et al., Symposium 3-CT-SY24, ADA 2016
ADA 2016 investor and analyst event
0
2
4
6
8
10
12
14
0 6 12 18 24 30 36 42 48 54
Months Months
HR = 0.85 95% CI (0.74;0.97)
p=0.017
HR = 0.87 95% CI (0.73;1.05)
p=0.14
Patients with an event (%)
Victoza® Placebo Patients with an event (%)
Victoza® Placebo
0
2
4
6
8
10
12
14
0 6 12 18 24 30 36 42 48 54
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0 4 8 1 2 1 6 2 0 2 4 2 8 3 2 3 6 4 0 4 4 4 8 5 2 5 6 6 0
0
5
1 0
1 5
2 0
2 5
3 0
3 5
4 0
4 5
5 0
5 5
6 0
6 5
Limited HbA1c difference, but lower severe hypoglycaemia rate and greater weight loss with Victoza® in LEADER trial
ADA 2016 investor and analyst event
Statistically significantly greater weight loss with Victoza®
Limited difference in HbA1c maintained throughout trial
Reduction in severe hypoglycaemia
ETD: estimated treatment difference, ie estimated mean change from baseline to month 36; ERR: estimated rate ratio Source: Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. 2016; In Press and Buse et al., Symposium 3-CT-SY24, ADA 2016
84
86
88
90
92
94
96
0 6 12 18 24 30 36 42 48
Months
Body weight (Kg) HbA1c (%)
Months
0
ETD: -0.40% 95% CI [-0.45;-0.34]
ETD: -2.26 kg 95% CI [-2.54;-1.99]
Victoza® Placebo
6
7
8
9
10
0 6 12 18 24 30 36 42 48 54
0
10
20
30
40
50
60
70
0 6 12 18 24 30 36 42 48
Mean episodes per 100 subjects
Months
ERR=0.68 95% CI (0.51;0.91)
0
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2
4
6
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16% reduction in overall microvascular events with Victoza® compared to placebo
Microvascular benefit is driven by 22% reduction in nephropathy
Victoza® reduced the risk of microvascular events in the LEADER trial driven by a reduction in nephropathy
HR: hazard ratio Source: Buse et al., Symposium 3-CT-SY24, ADA 2016
ADA 2016 investor and analyst event
Months
Months
Nep
hro
path
y
Reti
no
path
y
0
2
4
6
8
10
0 6 12 18 24 30 36 42 48 54
HR=0.84 95% CI (0.73;0.97)
p=0.016
HR = 0.78 95% CI (0.67;0.92)
p=0.003
Patients with an event (%)
Patients with an event (%)
HR = 1.15 95% CI (0.87;1.52)
p=0.33
0
2
4
6
8
10
0 6 12 18 24 30 36 42 48 54
Victoza® Placebo Victoza® Placebo
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Selected adverse events reported during the trial Safety conclusions
Victoza® appeared to have a safe and well tolerated profile in the LEADER trial
* One event of medullary thyroid carcinoma occured in the placebo arm, while none occurred in the Victoza® arm Source: Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. 2016; In Press
GI: gastrointestinal events MedDRA: medical dictionary for regulatory activities
ADA 2016 investor and analyst event
• In the LEADER trial, Victoza® appeared to have a safe and well tolerated profile, generally consistent with the previous Victoza® studies with a higher frequency of adverse events related to GI disorders and acute gallstone disease compared to placebo
• Pancreatic cancer events in the LEADER trial had the following distribution between the Victoza® and placebo arm respectively:
- Neoplasm adjudication: 13 vs 5 events
- Neoplasm + death adjudication: 13 vs 9 events
- MedDRA search in AE database (not adjudicated): 11 vs 10 events
Adverse event Victoza® Placebo P-value
Acute gallstone disease
3.1% 1.9% <0.001
Acute pancreatitis 0.4% 0.5% 0.44
Benign neoplasms 3.6% 3.1% 0.18
Malignant neoplasms 6.3% 6.0% 0.46
Pancreatic carcinoma 0.3% 0.1% 0.059
Medullary thyroid carcinoma* 0.0% 0.0% 0.32
Permanent discontinuation due to adverse events
9.5% 7.3% <0.001
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ADA 2016 investor and analyst event
SUSTAIN 2 and 3
Superior HbA1c and weight reduction with once-weekly injectable semaglutide
demonstrated in the SUSTAIN 2 and 3 trials and phase 2 results
from oral semaglutide
Alan Moses
SVP and chief medical officer
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Data from all SUSTAIN phase 3a trials for semaglutide to be presented at major conferences in 2016
Note: In the SUSTAIN phase 3a programme, 0.5 mg and 1.0 mg doses of semaglutide are being tested in people with type 2 diabetes n: number randomised patients ENDO: Endocrine Society Annual Meeting, April 2016; ADA: 76th Scientific Sessions, American Diabetes Association, June 2016; AACE: American Association of Clinical Endocrinologists 25th Annual Scientific and Clinical Congress, May 2016; EASD: 52nd Annual Meeting of the European Association for the Study of Diabetes, September 2016
ADA 2016 investor and analyst event
2013 2014 2015 2016
SUSTAIN 1: Monotherapy 30 weeks, n=388
SUSTAIN 2: Semaglutide vs sitagliptin 56 weeks, n=1,231
SUSTAIN 3: Semaglutide vs exenatide once-weekly 56 weeks, n=813
SUSTAIN 4: Semaglutide vs insulin glargine 30 weeks, n=1,089
SUSTAIN 5: Add-on to basal insulin 30 weeks, n=397
SUSTAIN 6: Long-term outcomes trial Min. 104 weeks, n=~3,300
Oral: ENDO 2016
Presentation
Oral: ADA 2016
Oral: ADA 2016
Poster: AACE 2016
Poster: EASD 2016
Oral: EASD 2016
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1 Inclusion criteria: Type 2 diabetes, age: 18 years or older, insulin-naïve on stable diabetes treatment with metformin, thiazolidinediones or metformin + thiazolidinediones 90 days prior to screening, HbA1c 7.0-10.5%. T2D: type 2 diabetes; QW: once weekly; QD: once daily Source: Ahrén, Oral 185-OR, ADA 2016
SUSTAIN 2 trial design Baseline characteristics
The SUSTAIN 2 trial compared the safety and efficacy of injectable semaglutide to sitagliptin 100 mg in T2D
Sema: semaglutide; BMI: body mass index; FPG: fasting plasma glucose
Sitagliptin 100 mg QD + semaglutide 0.5 mg placebo QW
Semaglutide 0.5 mg QW + sitagliptin placebo QD
0 56 weeks
1,231 insulin-naïve people with type 2 diabetes1
Semaglutide 1.0 mg QW + sitagliptin placebo QD
Sitagliptin 100 mg QD + semaglutide 1.0 mg placebo QW
Sema 0.5 mg
Sema 1.0 mg
Sitagliptin 100 mg
Mean age (years)
54.8 56.0 54.6
Mean diabetes duration (years)
6.4 6.7 6.6
Mean BMI (kg/m2)
32.4 32.5 32.5
Mean HbA1c 8.0% 8.0% 8.2%
Mean FPG (mmol/L)
9.3 9.3 9.6
ADA 2016 investor and analyst event
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* p<0.0001 when comparing semaglutide 0.5 mg and semaglutide 1.0 mg to sitagliptin 100 mg Source: Ahrén, Oral 185-OR, ADA 2016
Statistically significantly greater reduction in HbA1c with semaglutide
Statistically significantly greater weight loss with semaglutide
Semaglutide showed superior HbA1c and weight reduction compared to sitagliptin 100 mg in the SUSTAIN 2 trial
-7
-6
-5
-4
-3
-2
-1
0
0 8 16 24 32 40 48 56
Semaglutide 1.0 mg
Sitagliptin 100 mg
Semaglutide 0.5 mg Weight loss (Kg)
Weeks
-1.9
-4.3*
-6.1*
6.0
6.5
7.0
7.5
8.0
8.5
0 8 16 24 32 40 48 56
0.0
Semaglutide 1.0 mg
Sitagliptin 100 mg
Semaglutide 0.5 mg
HbA1c (%)
Weeks
7.5
6.8*
6.5*
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SUSTAIN 3 trial design Baseline characteristics
The SUSTAIN 3 trial compared the safety and efficacy of injectable semaglutide to exenatide 2.0 mg in T2D
1 Inclusion criteria: Type 2 diabetes, age: 18 years or older, stable treatment with 1-2 oral antidiabetic drugs (metformin, thiazolidinediones, sulfonylurea), HbA1c 7.0-10.5% T2D: type 2 diabetes; QW: once weekly Source: Ahmann, Oral 187-OR, ADA 2016
ADA 2016 investor and analyst event
Exenatide 2.0 mg QW
0 56 weeks
813 people with type 2 diabetes1
Semaglutide 1.0 mg QW
Sema: semaglutide; BMI: body mass index; FPG: fasting plasma glucose
Sema 1.0 mg
Exenatide 2.0 mg
Mean age (years) 56.4 56.7
Mean diabetes duration (years)
9.0 9.4
Mean BMI (kg/m2) 34.0 33.6
Mean HbA1c 8.4% 8.3%
Mean FPG (mmol/L) 10.6 10.4
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* p-value <0.0001 Source: Ahmann, Oral 187-OR, ADA 2016
Statistically significantly greater reduction in HbA1c with semaglutide
Statistically significantly greater weight loss with semaglutide
Semaglutide showed superior HbA1c and weight reduction versus exenatide once-weekly in the SUSTAIN 3 trial
-7
-6
-5
-4
-3
-2
-1
0
0 8 16 24 32 40 48 56
Weeks
-1.9
-5.6*
Weight loss (kg)
Semaglutide 1.0 mg Exenatide 2.0 mg Semaglutide 1.0 mg Exenatide 2.0 mg
6.0
6.5
7.0
7.5
8.0
8.5
0 8 16 24 32 40 48 56
0.0
HbA1c (%)
Weeks
7.4
6.8*
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0%
5%
10%
15%
20%
0 6 12 18 24 30 36 42 48 54 60
Rates of nausea with semaglutide in SUSTAIN 2 and 3 trials
GLP-1-related run-in side effects reduced through selected titration scheme in trials
Semaglutide appeared to have a safe and well tolerated profile in the SUSTAIN 2 and 3 trials
Semaglutide 1.0 mg
Sitagliptin 100 mg
Semaglutide 0.5 mg
Subjects experiencing nausea
Weeks GI: gastrointestinal
• Generally, semaglutide appeared to have a safe and well-tolerated profile in the SUSTAIN 2 and 3 trials
• While semaglutide caused more GI adverse events than sitagliptin and exenatide, GI disorders were similar to those reported with other GLP-1s
• Discontinuation rates due to adverse events for semaglutide were low indicating that regular GLP-1-related run-in side effects have been reduced through the selected titration scheme
Exenatide 2.0 mg
0%
5%
10%
15%
20%
0 6 12 18 24 30 36 42 48 54 60
ADA 2016 investor and analyst event
SUSTAIN 2
SUSTAIN 3
GLP-1: glucagon-like peptide-1 Source: Ahrén, Oral 185-OR and Ahmann, Oral 187-OR, ADA 2016
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1 Semaglutide sc arm was open-label, whereas all tablet arms were double-blind 2 Dosing conditions: Tablets administered in the fasting state, subjects abstained from food and fluid intake for at least 30 minutes after tablet ingestion 3 Inclusion criteria: type 2 diabetes, age: 18 years or older, BMI higher than 25 and lower than 40 kg/m2, treated with diet and exercise with or without metformin, HbA1c: 7.0-9.5% sc: subcutaneous; QW: once weekly; QD: once daily
Phase 2 trial design1,2 Baseline characteristics
Oral semaglutide in five daily doses compared with injectable semaglutide and placebo in phase 2 trial
Sema: semaglutide Source: Rosenstock et al., OR15-3, ENDO 2016
632 people with type 2 diabetes3
26 Weeks 0 4 8 12
0.25 0.5
5 10 20
5
2.5
10 5
2.5 mg
5 mg
10 mg
40 mg
20 mg
1.0 mg
Oral sema QD
Oral sema QD
Oral sema QD
Oral sema QD
Oral sema QD
Placebo QD
sc sema QW
Oral sema Placebo sc sema
Mean age (years)
55.7-58.3 58.9 56.8
Mean diabetes duration (years)
7.8-8.1 6.7 5.6
Body weight (kg) 90.9-93.8 93.8 88.8
Mean BMI (kg/m2)
31.1-32.0 32.6 30.7
Mean HbA1c 7.8-8.1% 8.0% 7.8%
Treated with metformin
84-87% 82% 84%
Placebo
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5.5
6.0
6.5
7.0
7.5
8.0
0 2 4 6 8 10 12 14 16 18 20 22 24 26
-8
-6
-4
-2
0
0 2 4 6 8 10 12 14 16 18 20 22 24 26
HbA1c reduction from a mean baseline of 7.9% Weight loss from a mean base line of 92 kg
Oral semaglutide dose dependently reduced HbA1c and body weight in phase 2 trial
Inclusion criteria: Type 2 diabetes, 7.0% ≤ HbA1c ≤ 9.5%, treatment with diet and exercise with or without metformin; sc: subcutaneous; sema: semaglutide Dotted line indicates the target for HbA1c of 7.0% as recommended by the American Diabetes Association Source: Rosenstock et al., OR15-3, ENDO 2016
ADA 2016 investor and analyst event
Placebo Sema 2.5 mg Sema 5 mg Sema 10 mg Sema 20 mg Sema 1 mg sc Sema 40 mg
HbA1c (%) Weight loss (kg)
0.0
Weeks Weeks
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GI adverse events with oral semaglutide were comparable to injectable semaglutide Safety conclusions
The safety and tolerability profile of oral semaglutide was similar to injectable semaglutide in phase 2 clinical trial
• Overall, oral semaglutide appeared to have a safe and well-tolerated profile in the trial
• GI adverse events with oral semaglutide were similar to injectable semaglutide
• Dose-dependent increase in discontinuation rates observed in the trial
• Only few events of pancreatitis, gallbladder disorders or malignant neoplasms were observed in the trial
GI: gastrointestinal; sc: subcutaneous Source: Rosenstock et al., OR15-3, ENDO 2016
0%
10%
20%
30%
40%
50%
Nausea Vomiting Diarrhea
Proportion of subjects
Placebo Sema 2.5 mg Sema 5 mg
Sema 10 mg Sema 20 mg Sema 40 mg
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Sema 1 mg sc
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Concluding remarks
PPG: postprandial plasma glucose; MACE: major adverse cardiovascular events; QW: once weekly
ADA 2016 investor and analyst event
Tresiba® demonstrated lower rates of hypoglycaemia than insulin glargine U100 in the SWITCH trials
Steady Tresiba growth in the US. In Japan Tresiba® market share continues to grow despite biosimilar launch
Early onset of faster-acting insulin aspart leads to improved HbA1c and PPG versus insulin aspart in onset 1 trial
Victoza® demonstrated statistically significant 13% reduction in MACE and reduced cardiovascular and all cause mortality statistically significantly by 22% and 15 %, respectively, compared to placebo in the LEADER trial
Semaglutide QW demonstrated superior HbA1c and body weight reductions against comparators in SUSTAIN 2 and 3
Oral semaglutide dose dependently reduced HbA1c and body weight in a 26-week phase 2 trial in type 2 diabetes
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Jakob Riis, EVP China, Pacific and Marketing
Mads Krogsgaard Thomsen, EVP and CSO
Peter Kurtzhals, SVP Global Research
Peter Kristensen, SVP Global Development
Alan Moses, SVP and CMO
ADA 2016 investor and analyst event
Q&A session
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Share information Investor Relations contacts
Investor contact information
ADA 2016 investor and analyst event
Novo Nordisk’s B shares are listed on the stock exchange in Copenhagen under the symbol ‘NOVO B’. Its ADRs are listed on the New York Stock Exchange under the symbol ‘NVO’. For further company information, visit Novo Nordisk on the internet at: novonordisk.com
Peter Hugreffe Ankersen +45 3075 9085 phak@novonordisk.com
Melanie Raouzeos +45 3075 3479 mrz@novonordisk.com
In North America:
Kasper Veje +1 609 235 8567 kpvj@novonordisk.com
Novo Nordisk A/S Investor Relations Novo Allé, DK-2880 Bagsværd
Upcoming events
05 Aug 2016 Financial statement for the first six months of 2016
28 Oct 2016 Financial statement for the first nine months of 2016
02 Feb 2017 Financial statement for 2016
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Appendix – Glossary
ADA 2016 investor and analyst event
Abbreviation Meaning Abbreviation Meaning Abbreviation Meaning
AACE American Association of Clinical Endocrinologists
FPG Fasting plasma glucose MS Market share
ADA American Diabetes Association GIR Glucose infusion rate NS Not statistically significant
BG Blood glucose GLP-1 Glucagon-like peptide-1 OAD Oral anti-diabetic agent
BMI Body mass index (kg/m2) HbA1c Glycated haemoglobin A1c PPG Postprandial glucose
BP Blood pressure HR Hazard ratio QD Once daily
CI Confidence interval IAsp Insulin aspart QW Once weekly
CV Cardiovascular IDeg Insulin degludec SC Subcutaneous
EASD European Association for the Study of Diabetes
IGlar Insulin glargine Sema Semaglutide
ENDO Endocrine Society MACE Major adverse cardiovascular event
T1D/T2D Type 1 diabetes/type 2 diabetes
ETD Estimated treatment difference MedDRA Medical dictionary for regulatory activities
TRx Total prescriptions