american diabetes association 76 scientific sessions ...€¦ · slide 1 5,05 4,10 3,50 4,72 11,82...

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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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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


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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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


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


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


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


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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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


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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


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


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


HbA1c reduction (%)

faster aspart (post meal)

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


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)



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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


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



12.8 12.9

Mean BMI (kg/m2) 32.5 32.5


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


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

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2

4

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0 18 36 54

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4

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0 18 36 54

0

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4

6

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0 18 36 54

All components of 3-point MACE contributed to the reduction in cardiovascular risk in the LEADER trial


Non-fatal stroke Cardiovascular death Non-fatal

myocardial infarction

Months Months Months


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


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


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


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


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


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

8

10

0 6 12 18 24 30 36 42 48 54

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


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



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


• 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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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


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


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


5,05

4,10

3,50

4,72

11,82 11,82

* 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*


5,05

4,10

3,50

4,72

11,82 11,82

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


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



9.0 9.4

Mean BMI (kg/m2) 34.0 33.6


Mean FPG (mmol/L) 10.6 10.4

5,05

4,10

3,50

4,72

11,82 11,82

* 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*


5,05

4,10

3,50

4,72

11,82 11,82

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


SUSTAIN 2

SUSTAIN 3

GLP-1: glucagon-like peptide-1 Source: Ahrén, Oral 185-OR and Ahmann, Oral 187-OR, ADA 2016

5,05

4,10

3,50

4,72

11,82 11,82

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


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


5,05

4,10

3,50

4,72

11,82 11,82

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


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

5,05

4,10

3,50

4,72

11,82 11,82

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


Sema 1 mg sc

5,05

4,10

3,50

4,72

11,82 11,82

Concluding remarks

PPG: postprandial plasma glucose; MACE: major adverse cardiovascular events; QW: once weekly


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

5,05

4,10

3,50

4,72

11,82 11,82

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


Q&A session

5,05

4,10

3,50

4,72

11,82 11,82

Share information Investor Relations contacts

Investor contact information


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 [email protected]

Melanie Raouzeos +45 3075 3479 [email protected]

In North America:

Kasper Veje +1 609 235 8567 [email protected]

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

mailto:[email protected]



5,05

4,10

3,50

4,72

11,82 11,82

Appendix – Glossary


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

american diabetes association 76 scientific sessions ...€¦ · slide 1 5,05 4,10 3,50 4,72 11,82...

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