2. Disclosures
Professor Giovannoni has received personal compensation for
participating on Advisory Boards in relation to clinical trial design,
trial steering committees and data and safety monitoring
committees from: Abbvie, Bayer-Schering Healthcare, Biogen-Idec,
Canbex, Eisai, Elan, Fiveprime, Genzyme, Genentech, GSK, GW
Pharma, Ironwood, Merck-Serono, Novartis, Pfizer, Roche,
Sanofi-Aventis, Synthon BV, Teva, UCB Pharma and Vertex
Pharmaceuticals.
Professor Giovannoni would like to acknowledge several
companies and colleagues for making available data slides for this
presentation.
19. Consequences of increasing EDSS scores: loss of employment
0
10
20
30
40
50
60
70
80
90
Work Capacity by Disability Level
0.0/1.0 2.0 3.0 4.0 5.0 6.0 6.5 7.0 8.0/9.0
EDSS Score
ProportionofMSers≤65YearsOld
Working(%)
The proportion of MSers employed or on long-term sick leave is calculated as a percentage of MSers aged 65 or younger.
1. Kobelt G et al. J Neurol Neurosurg Psychiatry. 2006;77:918-926;
2. Pfleger CC et al. Mult Scler. 2010;16:121-126.
Spain
Sweden
Switzerland
United Kingdom
Netherlands
Italy
Germany
Belgium
Austria
~10 yrs2
20. 57%
7%
-20%
0%
20%
40%
60%
CISers
n = 40
Feuillet et al. Mult Scler. 2007.
Healthy Controls
n = 30
p < 0.0001
Deficits were found mainly in memory, speed of information
processing, attention and executive functioning.
MSers failing
≥ 2 cognitive
tests
Cognition in early multiple sclerosis
21. Brain atrophy occurs across all stages of the disease
De Stefano, et al. Neurology 2010
n= 963 MSers
25. ‘Rebranding’ MS a dementia - definition of
dementia
Dementia is a loss of mental ability severe enough to interfere
with normal activities of daily living, lasting more than six
months, not present since birth, and not associated with a loss
or alteration of consciousness.
• Interfere with normal activities of daily living
• Physical
• Mental
• Social
• Occupational
• Lasting more than six months
• Not present since birth
• Not associated with a loss or alteration of consciousness
“Multiple sclerosis is therefore a preventable
dementia.”
DSM IV
31. Premyelinating oligodendrocytes
in chronic MS lesions1
Negative regulators of OPC
differentiation have been identified2,3
Investigating LINGO-1 as a target for
remyelination
and neuroprotection/neuroreparation
OPC=oligodendrocyte precursor cells; NCAM=neural cell adhesion molecule;
PSA=polysialic acid; RNAi=ribonucleic acid interference.
1. Chang A et al. N Engl J Med. 2002;346:165-173; 2. Adapted from Rudick RA et al. Expert Opin Biol Ther. 2008;8:1561-1570;
3. Mi S et al. Ann Neurol. 2009;65:304-315; 4. Mi S et al. Nat Neurosci. 2005;8:745-751; 5. Cadavid D et al. Presented at AAN; Philadelphia, USA; 2014:P2.262.
In vivo effects of anti-LINGO-1 in
rat optic nerve crush model5
Reduced neurodegeneration and
increased axonal outgrowth (arrows) vs
control
Control RNAiLINGO-1 RNAi
In vitro effects of LINGO-1 blockade4
Mature
oligodendrocy
te
OPCs
Differentiatio
n
LINGO-1,
PSA-NCAM,
Notch
Anti-LINGO-
1
treatment
Proximal Distal
Control
treatment
Fluorescein isothiocyanate-conjugated
cholera toxin B–labeled axons after optic
nerve crush and vehicle injection
32. Premyelinating oligodendrocytes
in chronic MS lesions1
Negative regulators of OPC
differentiation have been identified2,3
Investigating LINGO-1 as a target for
remyelination
and neuroprotection/neuroreparation
OPC=oligodendrocyte precursor cells; NCAM=neural cell adhesion molecule;
PSA=polysialic acid; RNAi=ribonucleic acid interference.
1. Chang A et al. N Engl J Med. 2002;346:165-173; 2. Adapted from Rudick RA et al. Expert Opin Biol Ther. 2008;8:1561-1570;
3. Mi S et al. Ann Neurol. 2009;65:304-315; 4. Mi S et al. Nat Neurosci. 2005;8:745-751; 5. Cadavid D et al. Presented at AAN; Philadelphia, USA; 2014:P2.262.
In vivo effects of anti-LINGO-1 in
rat optic nerve crush model5
Reduced neurodegeneration and
increased axonal outgrowth (arrows) vs
control
Control RNAiLINGO-1 RNAi
In vitro effects of LINGO-1 blockade4
Mature
oligodendrocy
te
OPCs
Differentiatio
n
LINGO-1,
PSA-NCAM,
Notch
Anti-LINGO-
1
treatment
Proximal Distal
Fluorescein isothiocyanate-conjugated
cholera toxin B–labeled axons after optic
nerve crush and vehicle injection
33. Anti-LINGO-1 results in remyelination in animal models of CNS
demyelination2
LPC=lysophosphatidylcholine/lysolecithin; mAb=monoclonal antibody.
Adapted from 1. Mi S et al. Nature Neurosci. 2004;7:221-228; 2. Mi S et al. Ann Neurol. 2009;65:304-315.
1 µm
Control mAb Anti-LINGO-1
1 µm
Cuprizone
LPC
*
*
*
*
Demyelinated axons
*Remyelinated axons
EAE
34. New phase 2 study designs: Acute optic neuritis
to assess neuroprotection and remyelination
1. Cadavid D et al. Presented at AAN; Philadelphia, USA; 2014:P2.262
2. Cadavid D et al. Presented at AAN; Washington, USA; 2015:P7.202.
RENEW1,2
Anti-LINGO-
1
(multi-
centre)
Anti-LINGO-1 (100 mg/kg IV Q4W
x 6)
Placebo (IV Q4W x 6)
Participants with
first episode of
unilateral AON
(n=82)
Randomised
within 4 weeks
of symptom
onset
Dosing period
20 weeks
Assessments at
24 and 32
weeks
3–5
days’
IV
steroid
s End of study
follow-up
32 weeks
Primary outcome: VEP
35. RENEW primary outcome: Anti-LINGO-1 and recovery of full-field VEP
latency in AON
*Adjusted mean change in optic nerve conduction latency of the affected eye compared with the unaffected fellow eye at baseline, Week 24
(ANCOVA), Week 32 (MMRM). ANCOVA=analysis of covariance; ITT=intent-to-treat; MMRM=mixed-effect model repeated measure; PP=per-
protocol.
Adapted from 1. Cadavid D et al. Presented at AAN; Washington, USA; 2015:P008; 2. Cadavid D et al. Presented at AAN; Washington, USA;
2015:P7.202.
Placebo 100 mg/kg anti-LINGO-1
25
20
15
10
5
0
PP ITT
22.24
14.69
20.83
17.34
Week 24
34%
Latency
recovery
P=0.05
17%
Latency
recovery
P=0.33
Adjustedmeanchangein
Full-fieldVEPlatency*(ms)
n=36 n=33 n=41 n=41
PP=Subjects who completed the study, did not miss >1 dose of treatment
and did not receive MS modifying therapy
ITT=All randomised subjects who received ≥1 dose of study treatment
PP ITT
22.35
13.22
21.15
15.08
Week 32
41%
Latency
recovery
P=0.01
29%
Latency
recovery
P=0.07
n=36 n=33 n=41 n=41
39. Acuteaxonal
transection
“Inflammatory scissors or shredder”
Acute neuroprotection
Axon
NO
Microglia
Na+
Na+/K+
ATPaseNaV1.6
Reverse
NCX
ATP
ATP
Ca2+
ATPase
Ca2+
Na+
NaV1.6
Na+
Figure courtesy of Dr Raju Kapoor
ATP=adenosine triphosphate; NaV1.6=Sodium channel, voltage gated, type VIII, alpha subunit; NCX=sodium-calcium exchanger.
1. BD Trapp et al. N Engl J Med. 1998;338:278-285; 2. Bittner S et al. Ther Adv Neurol Disord. 2013;6:322-336.
Acute neuroprotection: targeting axonal energy levels may
achieve acute neuroprotection1,2
40. Acute optic neuritis (AON) to assess phenytoin (neuroprotection)
Phenytoin
Participants with
AON N=86
Phenytoin (4 mg/kg OD)
Placebo
Randomised
within 2 wks
of symptom
onset
Treatment
period
3 months
Monitoring
period
3 months
Primary
outcome
measures
Primary outcome measure: RNFL thickness
RNFL thickness Macular volume
1. Kapoor R et al. Presented at AAN; Washington, USA; 2015; 2. https://clinicaltrials.gov/ct2/show/NCT01451593;
41. Primary outcome: RNFL
• Active-placebo
adjusted
difference 7.15 mm
(95% CI 1.08, 13.22
p=0.02)
• 30% reduction of
atrophy
in active group
• PP comparison:
Active-placebo
adjusted
difference 7.40 mm
(95% CI 0.76, 14.04
p=0.03)
50100150
RNFLaveragemm
Placebo Phenytoin
baseline UNaffected eye
Placebo Phenytoin
6m affected eye
Bars are standard errors around the unadjusted group means
42. Delayed/ongoing secondary
neurodegeneration1
“Post-inflammatory slow-burn”
Ongoing neuroprotection
TreatmentTargets
1. Inflammation2
a. Adaptive (B-cell follicles)3
b. Innate (activated microglia4 and
astrocytes5)
2. Axonal mechanisms6
a. Mitochondrial/energetics7
b. Axonal targets6
3. Remyelination8
4. Comorbidities/ageing (simvastatin)9
1. Trapp BD et al. N Engl J Med. 1998;338:278-285; 2. Loleit V et al. Curr Pharm Biotechnol. 2014;15:276–296; 3 Magliozzi R et al. Brain. 2007;130:1089-1104;
4. Rissanen E et al. J Nucl Med. 2014;55:939-944; 5. Mayo L et al. Nat Med. 2014;20:1147-1156; 6. Haines JD et al. Mt Sinai J Med. 2011;78:231-243;
7. Mahad D et al. Neuropathol Appl Neurobiol. 2008;34:577-589; 8. Münzel EJ et al. Drugs. 2013;73:2017-2029; 9. Chataway J et al. Lancet. 2014;383:2213-2221.
Targeting ongoing chronic neurodegeneration
43. Slide courtesy of Jeremy Chataway Chataway et al. Lancet 2014; 383: 2213–21.
BSI (Boundary Shift Integral)
Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive
multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial
48. Flipping the pyramid
IMS, immunosuppressant; TNF, tumour necrosis factor
Reproduced from Gut, Ordás I, Feagan BG and Sandborn WJ, 1754–63, 2011 with permission from BMJ Publishing Group Ltd.
Corticosteroids
+ IMS
Corticosteroids
TNF
antagonist
± IMS
Conventional
step care
Accelerated
step care
Moderate
Severe
Early top-down
Levelofdisease
Flipping the
pyramid
49.
50. Fingolimod
Fingolimod
Dimethyl
fumarate
Alemtuzumab
Natalizumab
Laquinimod
Daclizumab HYP
Rituximab
Cladribine
Teriflunomid
e
Ocrelizumab
Ofatumumab
Targeting immune regulation has been successful previously in RRMS
Lymph node
APC=antigen-presenting cell; B=B cell; BBB=blood-brain barrier; CD=cluster of differentiation; CNS=central nervous system; IFN=interferon; IL=interleukin; MØ=macrophage; NK=natural killer cell;
NO=nitric oxide; PC=plasma cell; S1P-R=Sphingosine-1-phosphate receptor; T=T cell; Th=T-helper cell; TNF=tumour necrosis factor; VCAM=vascular cell adhesion molecule; VLA=Integrin alpha4beta1.
Adapted from 1. Barten LJ et al. Drug Des Devel Ther. 2010;4:343-366; 2. Loleit V et al. Curr Pharm Biotechnol. 2014;15:276-296.
BBB CNSPeriphery
Approved
therapies
Investigational
agents
52. Immunomodulatory Effect of Daclizumab Treatment
DAC treatment increases CD56bright NK cell proliferation via intermediate affinity IL-2
signaling1
Martin J et. al., J. Immunol, 2010.
53. 53
Click to edit Master title styleDECIDE Study Design Overview
All patients had a minimum of 2 years and maximum of 3 years of treatment
The trial ended when the last patient randomized completed 2 years of treatment
96-144 week treatment period
RRMS Patients
(N=1841)
0 4 8 12 16 20 24 28 32 36 40 44 48 96 144
IM IFN beta-1a 30 mcg every 1 week (n=922)
SC DAC HYP 150 mg every 4 weeks (n=919)
Follow-up
Brain MRI
EDSS* EDSS* EDSS* EDSS* EDSS* EDSS*
*Also assessed at weeks 60, 72, 84, 108, 120, 132, 144. EDSS, Expanded Disability Status Scale; IFN, interferon; IM, intramuscular; mcg, micrograms;
MRI, magnetic resonance imagine; RRMS, relapsing remitting multiple sclerosis; SC, subcutaneous.
Inclusion Criteria:
• Age 18-55 years
• Confirmed RRMS1
• MRI consistent with MS
• Baseline EDSS 0-5
• ≥2 relapses within 3 years (≥1
in year prior to study)
• ≥1 relapse (or new MRI lesion)
within 2 years (≥1 in year prior
to study)
Time (weeks)
1:1 Randomization
53
54. 54
Click to edit Master title styleAnnualized Relapse Rate (ARR)
(n=922) (n=919)
ARR
Estimated from a negative binomial regression model adjusted for baseline relapse rate, history of prior IFN beta use, baseline EDSS (≤2.5 vs > 2.5) and baseline age
(≤35 vs >35). Patients were censored at the earliest of the following events: 1) start of alternative MS medication, 2) 180 days post treatment discontinuation or 3)
end of treatment period. CI, confidence interval.
54
55. 55
Click to edit Master title style
3-Month and 6-Month Confirmed Disability
Progression
Risk reduction: 16%; p=0.16
Proportion with progression
Week 48: 6% vs. 8%
Week 96: 12% vs. 14%
Week 144: 16% vs. 20%
BL 12 24 36 48 60 72 84 96 108 120 132 144
Time on study (weeks)
BL 12 24 36 48 60 72 84 96 108 120 132 144
Time on study (weeks)
Risk reduction: 27%; p=0.0332
Proportion with progression
Week 48: 4% vs. 7%
Week 96: 9% vs. 12%
Week 144: 13% vs. 18%
3-month* 6-month†
Proportionofpatientswith
confirmedprogressionofdisability
*3-month confirmed: Patients censored after tentative progression (n=67) analyzed per primary method in the statistical analysis plan: all imputed as non-progressors;
†6-month confirmed: Patients censored after tentative progression (n=108) imputed per observed rate in trial; tertiary endpoint. Estimated proportions are the average
over imputed datasets. For both endpoints risk reductions based on Cox proportional hazards model adjusted for baseline EDSS, history of prior IFN use, and age.
57. Ocrelizumab is a humanized mAb that depletes CD20+ B cells
via multiple mechanisms
57
mAb, monoclonal antibody.
1. Jaglowski SM, et al. Blood 2010;116:3705–14; 2. Winiarska M, et al. Front Biosci 2011;16277–306; 3. Klein C, et al. MAbs 2013;5:22–33.
COMPLEMENT-DEPENDENT
CYTOTOXICITY1-3
DIRECT
APOPTOSIS1-3
ANTIBODY-DEPENDENT
CELLULAR PHAGOCYTOSIS1-3
ANTIBODY-DEPENDENT
CELLULAR CYTOTOXICITY1-3
58. 58
B cells are depleted to a greater extent in lymphoid
compartments compared with bone marrow
58
LN-ing, lymph node-inguinal; LN-man, LN-mandibular.
Gelzleichter T, et al. ACTRIMS-ECTRIMS 2014; Poster 64654.
60. Cladribine is an analog of deoxyadenosine
• Cladribine is an analog of deoxyadenosine, one of the building blocks of DNA, that
differs from the naturally occurring nucleoside, deoxyadenosine by a chlorine
substitution for hydrogen1,2
• Cladribine is resistant to deamination by the enzyme adenosine deaminase (ADA) by
virtue of its structural design1,2
1. Carson DA et al. Proc Natl Acad Sci USA 1980;77:6865-9. 2. Beutler E. Lancet 1992;340:952-6
OH
HO
O
N NCI
N
NH2
N
2-chlorodeoxyadenosine
(cladribine)
OH
HO
O
N NH
N
NH
2
N
Deoxyadenosine
Nitrogenou
s
base
Sugar
Phosphate
Backbone
Base pair
Adenine
Ribose
61. Cladribine Tablets lead to reductions in CD4+ T and CD8+
T cells
Placebo
(n=79)
Cladribine Tablets 3.5 mg/kg
(n=81)
Months
0
100
200
300
400
500
600
700
800
900
1000
1 2 3 4 5 6 7 8 9 101112131415161718192021222324LA*
Cells/µL
0
50
100
150
200
250
300
350
400
450
500
1 2 3 4 5 6 7 8 9 101112131415161718192021222324LA*
Cells/µL
BLBL
Normal range:
500-1500/µL
Normal range:
300-1000/µL
CD4+ T cells CD8+ T cells
Months
Arrows indicate administration of Cladribine Tablets. 1 treatment week = 1 or 2 tablets over 4-5 days
during a 28-day period.
*LA performed at 26 months. BL, baseline; LA, last assessment.
Soelberg-Sørensen S et al. ENS 2009 [P359]. Leist TP, Weissert R. Clin Neuropharmacol 2011;34:28-35
62. Significant reduction in ARR vs
placebo over 2 years (primary endpoint)
0.33
0.14 0.15
Placebo
(n=437)
Cladribine
3.5 mg/kg
(n=433)
Annualizedrelapserate(95%CI)
Cladribine
5.25 mg/kg
(n=456)
(0.29, 0.38)
(0.12, 0.17)
(0.12, 0.17)
0.3
0
0.2
0
0.1
0
0.0
0
0.4
0
3.5 mg/kg vs placebo
57.6% relative
reduction
p<0.001
5.25 mg/kg vs
placebo
54.5% relative
reduction
p<0.001
ARR, annualized relapse rate.
Intent-to-treat population. Giovannoni G et al. N Engl J Med 2010;362:416-26
63. Significant delay in time to 3-month confirmed
disability progression (secondary endpoint)
Placebo
Cladribine Tablets 5.25 mg/kg
Cladribine Tablets 3.5 mg/kg
~30% reduction in
risk of developing
disability
progression at any
time point over 2
years
(96 weeks on
study)
Cladribine Tablets:
5.25 mg/kg and 3.5 mg/kg
10th percentile = 14.8 Study
months
Proportionof
patientswithprogression
0.0
0.1
0.2
0.3
0.4
0.5
0 4 14 16 24
Study months
2 6 8 10 12 18 20 22
Placebo:
10th percentile = 11.8 Study months
5.25 mg/kg vs
placebo
Hazard ratio: 0.69
95% CI: 0.49, 0.96
p=0.026a
3.5 mg/kg vs placebo
Hazard ratio: 0.67
95% CI: 0.48, 0.93
p=0.018a
Prolongation of time to
sustained disability
progression by ~3
months
aThe hazard ratio, 95% CI, and p-values were estimated using Cox proportional hazards model with fixed effects for treatment
group and region.
Intent-to-treat population. Giovannoni G et al. N Engl J Med 2010;362:416-26. Data on file
64. Significantly more patients achieve
NEDAa over 2 years vs placebo
15.8
44.3
46
0
10
20
30
40
50
60
Placebo
(n=379)
Cladribine 3.5
mg/kg (n=402)
ProportionofpatientswithNEDA
(%)
Cladribine 5.25
mg/kg
(n=411)
3.5 mg/kg vs placebo
Odds ratio: 4.28
95% CI: 3.05, 6.02
p<0.0001
5.25 mg/kg vs
placebo
Odds ratio: 4.62
95% CI: 3.29, 6.48
p<0.0001
NEDA, no evidence of disease activity.
Post hoc analysis. aNEDA was defined as having no relapses, no 3-month sustained change in EDSS score, no new T1 Gd+ lesions, and no
active T2 lesions. Giovannoni G et al. Lancet Neurol 2011;10:329-37
65. CLARITY EXT demonstrates the durable
efficacy of Cladribine Tablets on relapses and
reconfirms the efficacy outcomes of CLARITY
0.14 0.15 0.14 0.15
0.33
0.15 0.16
0.10 0.11 0.10
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
3.5 mg/kg CP 5.25 mg/kg CP 7 mg/kg CC 8.75 mg/kg CC 3.5 mg/kg PC
Cladribine Placebo
98 186 186 244437456456 433433 92
Annualizedrelapserate
n=
CLARITY
EXT
CLARITY CLARITY
EXT
CLARITY CLARITY
EXT
CLARITY CLARITY
EXT
CLARITY CLARITY
EXT
CLARITY
The similar ARRs seen in CLARITY and CLARITY EXT suggest that treatment with Cladribine Tablets leads to a
durable effect on ARR for up to 4 years. In addition, within-treatment group analysis of the 3.5 mg/kg PC group
(n=244)
demonstrated that switching to cladribine treatment in Years 3 and 4 led to a significant reduction in ARR in
patients previously treated with placebo in Years 1 and 2 (ARR fell from 0.25 to 0.10; p<0.001)a
CP=cladribine (3.5 mg/kg) in CLARITY, placebo in CLARITY EXT; PC=placebo in CLARITY, cladribine (3.5 mg/kg) in CLARITY EXT; CC=cladribine (3.5 or
5.25 mg/kg) in CLARITY, cladribine (3.5 mg/kg only) in CLARITY EXT. For each group, cladribine dose refers to cumulative dose over 4 years in
CLARITY EXT. ap-values for within-group comparisons were based on the two-sided Wilcoxon signed–rank test (see slide notes for more details).
Giovannoni G et al. N Engl J Med 2010;362:416-26. Giovannoni G et al. AAN 2013 [P07.119]
66. 100
90
80
70
60
50
40
30
20
10
0
M3 M6 M9 M12 M15 M18 M21 M24
Time to McDonald MS conversion from randomization date (Months)
203 (0) 165 (37) 119 (82) 113 (87) 108 (88) 87 (95) 71 (96) 39 (98) 1 (99)Cladribine 5.25 mg/kg
204 (0) 167 (36) 114 (88) 108 (92) 92 (102) 82 (104) 71 (107) 39 (110) 3 (110)Cladribine 3.5 mg/kg
201 (0) 143 (58) 71 (128) 58 (141) 43 (154) 32 (162) 23 (165) 13 (169) 2 (169)Placebo
Patients at risk
(conversions):
87.1%
51.4%
56.1%
Hazard ratio vs placebob
5.25 mg/kg: 0.425, p<0.0001
3.5 mg/kg: 0.496, p<0.0001
Cumulativeincidence(%)
Risk reduction
5.25 mg/kg: 57.5%
3.5 mg/kg: 50.4%
Treatment with Cladribine Tablets reduces the risk of conversion
to McDonald 2005 MS in treatment-naïve patients with an FCDEa
– Cladribine 5.25 mg/kg
– Cladribine 3.5 mg/kg
– Placebo
M0
aPatients enrolled in ORACLE-MS were treatment-naïve with an FCDE at high risk of converting to MS. bCox proportional hazards model controlling for the
randomization stratification factor (region). FCDE, first clinical demyelinating event; M, Month. Leist TP et al. Lancet Neurol 2014;13:257-67
75. Rapid adoption of innovations is “biggest unmet need
of all”
Adapted from Everett M. Rogers, Diffusion of Innovations
76. Large disparities exist in access to disease-modifying
therapies
1. Hollingworth S et al. J Clin Neurosci 2014;21:2083–7; 2. World Bank, 2015. http://data.worldbank.org/indicator/SP.POP.TOTL;
3. MSIF, 2013. http://www.atlasofms.org; 4. Wilsdon T et al. 2013. http://crai.com/sites/default/files/publications/CRA-Biogen-
Access-to-MS-Treatment-Final-Report.pdf
Australia
Norway
Denmark
Sweden
Belgium
Austria
Germany
France
Finland
Spain
Italy
Slovenia
United Kingdom
Poland
0 20 40 60 80 100
Newer DMT
Established DMT
No DMT
All people with MS (%)
All data are from 2013
4
4
4
4
4
4
4
4
4
4
4
4
4
1–3
Established DMTs
DMTs approved for relapsing
forms of MS during the 1990s
and reformulations or generic
versions of these substances.
Newer DMTs
DMTs approved for relapsing
forms of MS that have a
different mechanism of action
from established DMTs.
1st line
2nd line
3rd line
97. Conclusions: the ‘future’ in MS
• MS service development – ‘uberization’ of MS care
• Better symptomatic therapies
• Need quicker adoption of innovations
• Brain Health Policy (www.msbrainhealth.org)
• UK move up the league tables
• Affordable DMTs , particularly in resource-poor settings
• New legislation for repurposing of off-patent drugs
• New therapeutic targets
• Therapeutic pyramid
• Neuroprotection / Remyelination
• New trial design
• Brain Health
• New anti-inflammatories
• Daclizumab
• Ocrelizumab
• Cladribine
• Black Swan
• Viral and other hypotheses
• Prevention of MS
98. Conclusions: the ‘future’ in MS
• MS service development – ‘uberization’ of MS care
• Better symptomatic therapies
• Need quicker adoption of innovations
• Brain Health Policy (www.msbrainhealth.org)
• UK move up the league tables
• Affordable DMTs , particularly in resource-poor settings
• New legislation for repurposing of off-patent drugs
• New therapeutic targets
• Therapeutic pyramid
• Neuroprotection / Remyelination
• New trial design
• Brain Health
• New anti-inflammatories
• Daclizumab
• Ocrelizumab
• Cladribine
• Black Swan
• Viral and other hypotheses
• Prevention of MS