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Both teriflunomide and alemtuzumab are investigational treatments in phase III development. They are not approved by FDA nor EMA for use in MS Clinical implications: the potential of tailored MS treatment Gavin Giovannoni Blizard Institute of Cell and Molecular Science Barts and The London School of Medicine and Dentistry Queen Mary University of London, UK

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Presentation given at the Russian Neurological Society Meeting, Nizhniy Novogord, 18 June 2012.

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Page 1: Personalised Care

Both teriflunomide and alemtuzumab are investigational treatments in phase III development. They are not approved by FDA nor EMA for use in MS

Clinical implications: the potential of tailored MS treatment

Gavin Giovannoni

Blizard Institute of Cell and Molecular Science Barts and The London School of Medicine and Dentistry Queen Mary

University of London, UK

Page 2: Personalised Care

Disclosures

• This is presentation is part of a Genzyme sponsored symprosium

• Research support received from: Bayer-Schering Healthcare, Biogen-Idec, Merck Serono, Merz, Novartis, sanofi-aventis and Teva

• Personal compensation received for serving as a grant reviewer, from the Irish Science Foundation

• Personal compensation received for participating on advisory boards in relation to clinical trial design, trial steering committees and data and safety monitoring committees for: Bayer-Schering Healthcare, Biogen-Idec, Elan, Fiveprime, Genzyme, GlaxoSmithKline, GW Pharma, Ironwood, Merck Serono, Novartis, Roche, sanofi-aventis, Synthon BV, Teva, UCB Pharma and Vertex Pharmaceuticals

• Investigator, CARE-MS I and II studies

The views expressed in the following slide sets are those of the individual authors and do not necessarily reflect the views of sanofi-aventis or Genzyme

Page 3: Personalised Care

Primary Care Referral Diagnosis Minimalimpairment

Moderateimpairment

Severeimpairment

End oflife care

Prevention

Cognition

Depression

Fatigue

Bladder

Bowel

Sexual dysfunction Tremor

Pain

Swallowing

Spasticity

Falls

Balance problems

Insomnia

Restless legs

Studying

Employment

RelapsesDMTs

Fertility

Rehab

Suprapubiccatheter

ITB

Palliative Care

PhysioST

OTCNS

Counselling

Radiology

Neurophysiology

Clinical trials

Gait

A ‘holistic’ approach to MS

Page 4: Personalised Care

Theoretical model: treat early and aggressively and you prevent disability

Natural course of disease

Laterintervention

Latertreatment

Treatmentat diagnosis Intervention

at diagnosis

Time

Disease Onset

Dis

abili

ty

Page 5: Personalised Care

Who discusses mortality with their patients?

Page 6: Personalised Care

Primary Care Referral Diagnosis Minimalimpairment

Moderateimpairment

Severeimpairment

End oflife care

Prevention

Cognition

Depression

Fatigue

Bladder

Bowel

Sexual dysfunction Tremor

Pain

Swallowing

Spasticity

Falls

Balance problems

Insomnia

Restless legs

Studying

Employment

RelapsesDMTs

Fertility

Rehab

Suprapubiccatheter

ITB

Palliative Care

PhysioST

OTCNS

Counselling

Radiology

Neurophysiology

Clinical trials

Gait

A ‘holistic’ approach to MS

Page 7: Personalised Care
Page 8: Personalised Care
Page 9: Personalised Care

Survival in MSers is shortened by 8 to 12 yearsSurvival Probability of Norwegian Patients with RRMS

(Hordaland County, Western Norway, 1953–2003)

RRMS=relapsing-remitting MS.Adapted from Torkildsen NG et al. Mult Scler. 2008;14:1191-1198.

500 5 10 15 20 25 30 35 40 450

10

20

30

40

50

60

70

80

90

100

Surv

ival

(%)

Years After Onset

30 35 40 45 50 55 60 65 70 75 80Approximate Patient Age

General PopulationRRMS95% CI

Page 10: Personalised Care

The survival disadvantage in MS is greater than in other chronic diseases

Standardized Mortality Ratios in Chronic Diseases

Disease SMR (range)

Cardiovascular disease1* 1.34 (1.23–1.44)

Ischemic stroke2† 1.75(1.38–2.19)

Early breast cancer3 2.0 (1.6–2.7)

Crohn’s disease4 2.8

MS5 2.8 (2.6–3.1)

MS (2–9.9 years after diagnosis)5 2.4 (1.9–2.9)

MS (≥10 years after diagnosis)5 3.1 (2.8–3.4)

Parkinson’s disease6 3.66 (3.37–3.95)

Type 2 diabetes1 4.47 (3.91–5.10)

*In patients with type 2 diabetes; †in patients with valvular heart disease in Olmsted County, Minnesota.1. De Marco R et al. Diabetes Care. 1999;22:756-761; 2. Petty DW et al. Mayo Clin Proc. 2005;80:1001-1008; 3. Hooning MJ et al. Int J Radiat Oncol Biol Phys. 2006;64:1081-1091; 4. South East England Public Health Observatory, Mortality trends. 2006; 5. Sumelahti ML et al. Mult Scler. 2010;16:1437-1442; 6. Hristova DR. Folia Medica. 2009;51:40-45.

Page 11: Personalised Care

21-year long-term follow-up of IFNb-1b studytime from study randomization to death

Early treatment (3 years) with IFNb-1b was associated with a 47% reduction in the risk of dying over 21 years compared with initial placebo treatment

Source: Poster Goodin et al. Neurology. 2012 Apr 24;78(17):1315-22. 

At risk:IFNB-1b 250 µgPlacebo

124123

124120

121117

118109

10488

HR=0.532 (95% CI: 0.314–0.902)46.8% reduction in hazard ratio Log rank, P=0.0173

IFNB-1b 250 µg

Placebo

0 2 4 6 8 10 12 14 16 18 20 2265%

70%

75%

80%

85%

90%

95%

100%

Time (Years)

Pro

po

rtio

n o

f p

ati

en

ts w

ho

are

sti

ll a

live

Page 12: Personalised Care

Who discusses employment with their patients?

Page 13: Personalised Care

Primary Care Referral Diagnosis Minimalimpairment

Moderateimpairment

Severeimpairment

End oflife care

Prevention

Cognition

Depression

Fatigue

Bladder

Bowel

Sexual dysfunction Tremor

Pain

Swallowing

Spasticity

Falls

Balance problems

Insomnia

Restless legs

Studying

Employment

RelapsesDMTs

Fertility

Rehab

Suprapubiccatheter

ITB

Palliative Care

PhysioST

OTCNS

Counselling

Radiology

Neurophysiology

Clinical trials

Gait

A ‘holistic’ approach to MS

Page 14: Personalised Care

Unemployment

Pfleger et al. Mult Scler. 2010;16:121-126.

0 5 10 15 20 25

Time (years)

0

0.2

0.4

0.6

0.8

1.0

Prob

abili

ty

Control PersonsMS Patients

Probability of Remaining in Active Employment After Onset of MS

Page 15: Personalised Care

Who discusses relationships with their patients?

Page 16: Personalised Care

Primary Care Referral Diagnosis Minimalimpairment

Moderateimpairment

Severeimpairment

End oflife care

Prevention

Cognition

Depression

Fatigue

Bladder

Bowel

Sexual dysfunction Tremor

Pain

Swallowing

Spasticity

Falls

Balance problems

Insomnia

Restless legs

Studying

Employment

RelapsesDMTs

Fertility

Rehab

Suprapubiccatheter

ITB

Palliative Care

PhysioST

OTCNS

Counselling

Radiology

Neurophysiology

Clinical trials

Gait

A ‘holistic’ approach to MS

Page 17: Personalised Care

Divorce and separation

*Life table method.Pfleger et al. Mult Scler. 2010; 16:121-126.

0 5 10 15 20 25

Time to Event or End of Observation (years)

0

0.2

0.4

0.6

0.8

1.0

Prob

abili

ty

Population ControlsMSers

Crude probability of remaining in a relationship after onset of MS*

Page 18: Personalised Care

Who discusses QoL with their patients?

Page 19: Personalised Care

The effect of MS on Quality of Life

• MS is one of the most common causes of neurological disability in young adults2

• Natural history studies indicate that it takes a median time of 8, 20, and 30 years to reach the irreversible disability levels of EDSS scores 4.0, 6.0, and 7.0, respectively3

*Utility measures are derived from EQ-5D using the EuroQoL instrument; †error bars depict 95% CIs. Half points on EDSSare not shown on graph axis, except at EDSS score 6.5.EDSS=Expanded Disability Status Scale; EQ-5D=European Quality of Life-5 Dimensions; QoL=quality of life.1. Adapted from Orme M et al. Value In Health. 2007;10:54-60; 2. WHO and MS International Foundation (MSIF). http://apps.who.int/bookorders/anglais/detart1.jsp?sesslan=1&codlan=1 &codcol=15&codcch=747. Accessed March 6, 2012;3. Confavreaux C et al. Brain 2003; 176:770-782. 4. Compston A, Coles A. Lancet. 2008;372:1502-1517.

Util

ity

EDSS and Utility* Show a Significant Inverse Relationship1†

Util

ity

EDSS Status

0.0 1.0 2.0 3.0 4.0 5.0 6.0 6.5 7.0 8.0 9.0–0.4–0.3–0.2–0.1

00.10.20.30.40.50.60.70.80.9

Page 20: Personalised Care

Who of you routinely measures blood vitamin D levels in people with MS?

Page 21: Personalised Care

Primary Care Referral Diagnosis Minimalimpairment

Moderateimpairment

Severeimpairment

End oflife care

Prevention

Cognition

Depression

Fatigue

Bladder

Bowel

Sexual dysfunction Tremor

Pain

Swallowing

Spasticity

Falls

Balance problems

Insomnia

Restless legs

Studying

Employment

RelapsesDMTs

Fertility

Rehab

Suprapubiccatheter

ITB

Palliative Care

PhysioST

OTCNS

Counselling

Radiology

Neurophysiology

Clinical trials

Gait

A ‘holistic’ approach to MS

Page 22: Personalised Care
Page 23: Personalised Care
Page 24: Personalised Care

Fracture risk in multiple sclerosis

Dobson et al. Submitted 2012.

Page 25: Personalised Care

Osteoporosis in multiple sclerosis

Dobson et al. Submitted 2012.

Page 26: Personalised Care

Treatment Strategy

Page 27: Personalised Care

DMT, disease-modifying therapies; EDSS, Expanded Disability Status Scale.1 Adapted from Compston A et al. Lancet 2008;372:1502–17; 2 O’Connor P et al. Lancet Neurol 2009;8:899–897

The natural course of relapsing-remitting MS1

MRI Events

Secondary progressiveFirst

clinicalevent

Time (years)

Relapsing-remitting

Pre-clinical

Inflammation

Disability

Brain volume

Axonal loss

Dis

ease

Sev

erity

Despite treatment, approximately one quarter (21–27%) of patients worsened by ≥1 point on the EDSS within 2 years2

Despite DMT, disease often continues to progress

Page 28: Personalised Care

Who monitors prognostic factors of a treatment response to DMTs?

Page 29: Personalised Care

Primary Care Referral Diagnosis Minimalimpairment

Moderateimpairment

Severeimpairment

End oflife care

Prevention

Cognition

Depression

Fatigue

Bladder

Bowel

Sexual dysfunction Tremor

Pain

Swallowing

Spasticity

Falls

Balance problems

Insomnia

Restless legs

Studying

Employment

RelapsesDMTs

Fertility

Rehab

Suprapubiccatheter

ITB

Palliative Care

PhysioST

OTCNS

Counselling

Radiology

Neurophysiology

Clinical trials

Gait

A ‘holistic’ approach to MS

Page 30: Personalised Care

Breakthrough disease after treatment initiation

Patients with breakthrough disease can be identified with• Clinical measures

– Relapses– EDSS progression

• MRI measures– T2 and Gd+ lesions

• Biological markers– IFNβ NAbs/lack of MxA gene induction– Natalizumab antibodies

Gd+=gadolinium-enhancing; IFNβ=interferon beta; NAbs=neutralizing antibodies; Abs=antibodies; MxA= myxovirus protein A.

Page 31: Personalised Care

Relapse on IFNβ therapy increases risk of sustained disability progression

• Risk is not much greater for 2 relapses or more• Sensitivity is only 50%

HR=hazard ratio; SE=standard error.Bosca et al. Mult Scler. 2008;14:636-639.

HR SE P Value 95% CI

No relapses (reference=1) 1

One relapse 3.41 1.47 0.005 1.46–7.98

Two or more relapses 4.37 1.74 0.000 1.90–9.57

HR of EDSS Increase in Patients with No Relapses, 1 Relapse, and 2 or More Relapses During the First 2 Years of IFN Treatment

0 20 40 60 80

0

0.25

0.50

0.75

Analysis Time (Months)

No RelapsesOne RelapseTwo or More Relapses

1.00

EDSS

Pro

gres

sion

Surv

ival

Pro

babi

lity

Page 32: Personalised Care

Strongest predictor of disability progression on IFNβ therapy is progression itself

Disease Activity During 2 Years of Treatment and Prediction of Disability Progression* at 6 Years

GroupSensitivity (%)

(CI)Specificity (%)

(CI)

A. An increase of at least one EDSS step confirmed at 6 months 85 (64–95) 93 (86–97)

B. Occurrence of any relapse 80 (58–92) 51 (41–61)

C. Occurrence of two or more relapses 45 (26–66) 81 (72–82)

D. A decrease in relapse rate less than 30% compared with 2 years before therapy 40 (22–61) 86 (77–91)

E. A decrease in relapse rate less than 50% compared with 2 years before therapy 40 (–61) 81 (72–88)

F. No decrease or identical relapse rate compared with 2 years before therapy 35 (18–57) 88 (79–93)

G. Definition A or B 90 (70–97) 48 (38–58)

H. Definition A or E 85 (64–95) 76 (66–83)

I. Definition A and B 75 (53–89) 97 (91–99)

J. Definition A and E 40 (22–61) 99 (94–99)

*EDSS score ≥6.0 or increase in at least 3 EDSS steps.Río J et al. Ann Neurol. 2006;59:344-352.

Page 33: Personalised Care

Study or SubgroupOdds Ratio

IV, Random, 95% CIKinkel 2008

Prosperini 2009Total (95% CI) 9.86 (2.33, 41.70)

Dobson et al. Submitted 2012.

MRI to monitor treatment response toIFNβ: a systematic review

Study or SubgroupOdds Ratio

IV, Random, 95% CIKinkel 2008

Pozzilli 2005Prosperini 2009

Sormani 2011Total (95% CI) 2.69 (0.72, 10.04)

0.01 0.1 1 10 100Disease Less Likely Disease More Likely

One New T2 Lesion

Favors Experimental Favors Control1001010.10.01

Two or More New T2 Lesions

Page 34: Personalised Care

Study or SubgroupOdds Ratio

IV, Random, 95% CIKinkel 2008

Rio 2008

Total (95% CI) 5.46 (2.48, 12.04)

MRI to monitor treatment response toIFNβ: a systematic review

Dobson et al. Submitted 2012.

Study or SubgroupOdds Ratio

IV, Random, 95% CIKinkel 2008

Pozzilli 2005Tomassini 2006

Total (95% CI) 3.34 (1.36, 8.22)

0.01 0.1 1 10 100Disease Less Likely Disease More Likely

One New Gd+ Lesion

0.01 0.1 1 10 100

Disease Less Likely Disease More Likely

Two or More New Gd+ Lesions

Page 35: Personalised Care

Clinical importance of neutralising antibodies against IFN-beta on relapses

Sorensen et al. Lancet 2003; 362: 1184–91.

Page 36: Personalised Care

Mean change in EDSS

Malluci et al. Neurology 2004.

Page 37: Personalised Care

Predictors of long-term clinical response to interferon beta therapy in relapsing multiple sclerosis

Tomassini et al. J Neurol (2006) 253 : 287–293.

Page 38: Personalised Care

How to improve adherence to DMTs?

Page 39: Personalised Care

DMT, disease-modifying therapy; IFN, interferon; GA, glatiramer acetateGiovannoni & Waubant, MSJ 2012

Systematic review of DMTs: treatment discontinuation by study type

70

60

50

40

30

20

10

0

Patie

nts

disc

ontin

uing

trea

tmen

t (%

)

IFNβ-1a30 µg IM

q.w.(n=5898)

IFNβ-1a44 µg SC

t.i.w.(n=3446)

IFNβ-1b250 µg SC

e.o.d.(n=3942)

GA20 µg SC

o.d.(n=2855)

70

60

50

40

30

20

10

0

Patie

nts

disc

ontin

uing

trea

tmen

t (%

)

IFNβ-1a30 µg IM

q.w.(n=5836)

IFNβ-1a44 µg SC

t.i.w.(n=3124)

IFNβ-1b250 µg SC

e.o.d.(n=3482)

GA20 µg SC

o.d.(n=2628)

≤12 months13–24 months>24 months

Randomised controlled trialObservational study

• Treatment discontinuation was frequent in both randomised controlled trials and observational studies

• Up to 40% of patients discontinue treatment within the first 2 years

Studies included ranged from January 1993 – October 2008

Page 40: Personalised Care

Impact of IFN-β adherence on relapse rateRe

lativ

e ris

k of

rela

pse

N=1606, 2006−2008; *includes all licensed IFN-β drugs excluding Extavia®IFN, interferon; MPR, medication possession ratioSteinberg SC et al. Clin Drug Investig 2010;30:89–100

1.15

1.10

1.05

1.00

0.95

0.90

>85% <80% <75% <70% <65% <60%

4% of patients had MPR >85%, on average 72−76%

Medication possession ratio (MPR)

• Poor adherence to IFN-β* increases relapse rate and healthcare resource utilisation

Page 41: Personalised Care

Other

Pregnancy/planned pregnancy

Nobody available to administer

Not confident in treatment benefits

Financial reasons

Did not pick up medication

Dosing schedule difficult/inconvenient

Forgot to administer

Did not feel need for injection

Depression

Weakness

Skin reaction

Injection anxiety

Headache

Pain at injection site

Flu-like symptoms

Fatigue

Tired of taking injections

0 10 20 30 40 50 60

17

1

2

2

3

5

10

50

4

6

8

9

10

10

12

13

15

20

Patient factors

Injection/tolerability factors

Patients (%)

32% of patients: at least one injection-related reason

84% of patients: other various reasons

The Global Adherence Project (GAP): reasons for non-adherence

Patients may report more than one reason

Devonshire V et al. Eur J Neurol 2011;18:69–77

Other

N=2648

Page 42: Personalised Care

Who engages patients in the decision making process concerning their treatment?

Page 43: Personalised Care

Concordance modelCompliance model

Prescriber decides diagnosis and treatment

Prescriber’s task is to explain and instruct

Patient’s task is to comprehend

Successful outcome is compliance

Prescriber and patient negotiate diagnosis and treatment

Prescriber elicits, explains, persuades and accommodates

Patient explains, considers and accommodates

Successful outcome is a negotiated agreement

From Compliance to Concordance. Pharmaceutical Journal 1997;259:860–861

Moving from compliance to concordance requires a culture change

Page 44: Personalised Care

Considerations prior to tailoring individualised treatment

Patient’s own treatment goals

OtherPatient’s own risk/benefit

tolerance

Patient’s own disease profile /characteristics

Individualised treatment

Treatment strategy

(e.g. induction vs escalation)

Economic factors

Increasingly complex

environment

Patient’s prior adherence to monitoring or drug regimen

• Many considerations are specific to patients’ needs and need to be layered withphysician-specific factors (e.g. treatment strategies) and economic factors 44

Page 45: Personalised Care

The large majority of MS patients want to be more actively involved in decision making

• In MS, 79% of patients prefer taking an active role in decision making about their condition

*Includes informed choice and shared decision-makingHeesen C et al. J Neurol Sci 2007;259:109–17

Autonomous Active role* Professional as agent

Paternalistic0

20

40

60

80

100

120

140

Num

ber o

f pati

ents

Page 46: Personalised Care

Listening to patients’ needs

• Several resources available to help patients understand treatment options and to map disease progression on current treatment– One-to-one counselling– Expert patient programmes– Online resources– Smartphone app in development– Education on available therapies and their

benefit/risk profiles

www.slcmsr.net/public

www.patientslikeme.com; www.msdecisions.org.uk; www.slcmsr.net/public

Page 47: Personalised Care

Case scenarios

Page 48: Personalised Care

Case studies: high risk CIS (?)

CIS – high risk/RMS (McDonald positive under new criteria1)• 28-year-old woman• Married with a young child• Presented with numbness/

muscle weakness and nausea• Several T2 and Gd-enhancing

lesions on MRI• Has done considerable

web-based research into her condition and understands risks of disease-progression

CIS, clinically isolated syndrome; IFN, interferon; GA, glatiramer acetate; 1 Polman CH et al. Ann Neurol 2011;69:292–302†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets

Page 49: Personalised Care

Case studies: high risk CIS (?)

CIS – high risk/RMS (McDonald positive under new criteria1)• 28-year-old woman• Married with a young child• Presented with numbness/

muscle weakness and nausea• Several T2 and Gd-enhancing

lesions on MRI• Has done considerable

web-based research into her condition and understands risks of disease-progression

Current (2012) therapy

IFN-β / GA

Possibly Fingolimod*

CIS, clinically isolated syndrome; IFN, interferon; GA, glatiramer acetate;* In countries with a 1st-line license 1 Polman CH et al. Ann Neurol 2011;69:292–302†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets

Page 50: Personalised Care

IFN-β / GA

Possibly Fingolimod*

Case studies: high risk CIS (?)

CIS – high risk/RMS (McDonald positive under new criteria1)• 28-year-old woman• Married with a young child• Presented with numbness/

muscle weakness and nausea• Several T2 and Gd-enhancing

lesions on MRI• Has done considerable

web-based research into her condition and understands risks of disease-progression

Current (2012) therapy Future (2013) therapy

IFN-β / GAFingolimod

BG-12†

Teriflunomide†

Alemtuzumab†

CIS, clinically isolated syndrome; IFN, interferon; GA, glatiramer acetate; 1 Polman CH et al. Ann Neurol 2011;69:292–302†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets

Page 51: Personalised Care

Case studies: Newly diagnosed RRMS

Newly diagnosed RRMS with extensive risk factors• 52-year-old

African-American man• Two attacks within

6 months• High BoD on MRI• EDSS 3.0• Recovery from attacks has

been poor with impact on motor function and some loss of bladder control

• JC virus antibody positive

BoD, burden of disease; EDSS, extended disability status scale; GA, glatiramer acetate**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets

Page 52: Personalised Care

Case studies: Newly diagnosed RRMS

Newly diagnosed RRMS with extensive risk factors• 52-year-old

African-American man• Two attacks within

6 months• High BoD on MRI• EDSS 3.0• Recovery from attacks has

been poor with impact on motor function and some loss of bladder control

• JC virus antibody positive

Current (2012) therapy

High-dose IFN-β / GAFingolimod**Natalizumab

BoD, burden of disease; EDSS, extended disability status scale; GA, glatiramer acetate**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets

Page 53: Personalised Care

Case studies: Newly diagnosed RRMS

Newly diagnosed RRMS with extensive risk factors• 52-year-old

African-American man• Two attacks within

6 months• High BoD on MRI• EDSS 3.0• Recovery from attacks has

been poor with impact on motor function and some loss of bladder control

• JC virus antibody positive

Current (2012) therapy Future (2013) therapy

High-dose IFN-β / GAFingolimod**Natalizumab

High-dose IFN-β / GABG-12†

Fingolimod†

Teriflunomide†

Natalizumab†

Alemtuzumab†

BoD, burden of disease; EDSS, extended disability status scale; GA, glatiramer acetate**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets

Page 54: Personalised Care

RRMS – stable with poor adherence• 44-year-old woman• No relapses in past 2 years• No new lesions on MRI, but

evidence of increasing lesion volume

• Often forgets to administer injections “my disease is stable”

• Has experienced injection-site reactions in the past

Case studies: RRMS – stable with poor adherence

RRMS, relapsing remitting multiple sclerosis; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets

Page 55: Personalised Care

RRMS – stable with poor adherence• 44-year-old woman• No relapses in past 2 years• No new lesions on MRI, but

evidence of increasing lesion volume

• Often forgets to administer injections “my disease is stable”

• Has experienced injection-site reactions in the past

Current (2012) therapy

IFN-β / GA + MS nurse supportFingolimod**

Case studies: RRMS – stable with poor adherence

RRMS, relapsing remitting multiple sclerosis; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets

Page 56: Personalised Care

RRMS – stable with poor adherence• 44-year-old woman• No relapses in past 2 years• No new lesions on MRI, but

evidence of increasing lesion volume

• Often forgets to administer injections “my disease is stable”

• Has experienced injection-site reactions in the past

Current (2012) therapy Future (2013) therapy

IFN-β / GA + MS nurse supportFingolimod**

IFN-β / GA BG-12†

Fingolimod†

Teriflunomide†

Case studies: RRMS – stable with poor adherence

RRMS, relapsing remitting multiple sclerosis; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets

Page 57: Personalised Care

Case studies: RRMS breakthrough disease

RRMS – breakthrough disease• 47-year-old woman• Active lifestyle and keen to

retain independence• Failed on one IFNβ• Diagnosed 3 years ago• Several relapses and marked

disability progression since diagnosis EDSS = 4.0

• On-going MRI disease activity• Has researched and accepts

benefit/ risk profiles of new treatments

EDSS, extended disability status scale; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets

Page 58: Personalised Care

Case studies: RRMS breakthrough disease

RRMS – breakthrough disease• 47-year-old woman• Active lifestyle and keen to

retain independence• Failed on one IFNβ• Diagnosed 3 years ago• Several relapses and marked

disability progression since diagnosis EDSS = 4.0

• On-going MRI disease activity• Has researched and accepts

benefit/ risk profiles of new treatments

IFN-β / GA Fingolimod*Natalizumab

Current (2012) therapy

EDSS, extended disability status scale; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets

Page 59: Personalised Care

Case studies: RRMS breakthrough disease

RRMS – breakthrough disease• 47-year-old woman• Active lifestyle and keen to

retain independence• Failed on one IFNβ• Diagnosed 3 years ago• Several relapses and marked

disability progression since diagnosis EDSS = 4.0

• On-going MRI disease activity• Has researched and accepts

benefit/ risk profiles of new treatments

IFN-β / GA Fingolimod*Natalizumab

Current (2012) therapy

IFN-β / GANatalizumab

BG-12†

Teriflunomide†

Fingolimod†

Alemtuzumab†

Future (2013) therapy

EDSS, extended disability status scale; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets

Page 60: Personalised Care

Conclusions

Page 61: Personalised Care

Summary and conclusions

Both teriflunomide and alemtuzumab are investigational treatments in phase III development. They are not approved by FDA nor EMA for use in MS

• MS is a bad disease

• Prognostic factors

• Treatment response markers

• Current DMTs have not been able to halt disease progression and carry a burden of adherence partly linked to injections

• Teriflunomide , Alemtuzumab and other emerging agents help address these needs

• As the disease profile and treatment needs of each patient differs, different therapy profiles will be of value

• Risk factors and patient views and the addition of new drugs to the treatment armamentarium will increase individualised treatment