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Phase 2 Results of the RADIANCE Trial: A Randomized,
Double-Blind, Placebo-Controlled Trial of Oral RPC1063
in Relapsing Multiple Sclerosis
Amit Bar-Or, MD
September 13, 2014
1
Cleveland Clinic, Mellen Center for MS Treatment and Research, Cleveland, OH, United States
2
NeuroRx Research, Montreal, QC, Canada
3
McGill University, Montreal, QC, Canada
4
San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Neurology, Milan, Italy
5
Montreal Neurological Institute, Department of Neurology and Neurosurgery, Montreal, QC, Canada
6
Receptos, Inc., Clinical Development, San Diego, CA, United States
7
Medical University of Lodz, Department of Neurology, Lodz, Poland
J Cohen
1
, DL Arnold
2,3
, G Comi
4
, A Bar-Or
5
, S Gujrathi
6
, JP Hartung
6
, A Olson
6
,  
M Cravets
6
, PA Frohna
6
, K Selmaj
7
Exhibit 99.1
2014 Joint ACTRIMS-ECTRIMS Meeting
Boston, Massachusetts


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ACTRIMS-ECTRIMS 2014
Conflict of Interest Statements
Amit Bar-Or
:
financial
support
from
Biogen
Idec,
DioGenix,
Genentech,
GlaxoSmithKline, Guthy-Jackson Charitable Foundation, Medimmune,
Merck Serono, Novartis, Ono Pharmaceuticals, Receptos, Roche, Sanofi-
Aventis, and Teva Neuroscience
J
Cohen
:
financial
support
from
EMD
Serono,
Receptos,
Genzyme/Sanofi,
Innate Immunotherapeutics, Novartis
DL Arnold
:
financial
support
from
Receptos
G
Comi
:
financial
support
from
Receptos
K Selmaj
:
financial
support
from
Biogen
Idec,
Novartis,
Genzyme,
Synthon, Roche, Merck, Receptos, Teva
S Gujrathi,
JP
Hartung,
A
Olson,
M
Cravets
&
PA
Frohna
are
full-time
employees of Receptos


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ACTRIMS-ECTRIMS 2014
Introduction
Immunomodulation through the sphingosine 1-phosphate
(S1P) receptor family is a validated therapeutic approach
for the treatment of relapsing multiple sclerosis (RMS)
RPC1063 is a novel, oral S1P
1,5R
modulator in clinical
development for RMS by Receptos, Inc., which has only
been previously tested as single and multiple doses in
healthy volunteer subjects
The Phase 2 results presented today are from the
RADIANCE trial: an ongoing international, combined
Phase 2/3 trial of RPC1063 in adult patients with RMS


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ACTRIMS-ECTRIMS 2014
RADIANCE Patient Population: Key Inclusion Criteria
MS, as diagnosed by the revised McDonald criteria (2010)
Exhibiting
a
relapsing
clinical
course
consistent
with
RMS
and
history
of brain MRI lesions consistent with MS
Ages 18-55 years, inclusive
EDSS at Baseline between 0 and 5.0 points, inclusive
Meet 1 of the following RMS disease activity criteria:
At least 1 documented relapse within the last 12 months
OR
At least 1 documented relapse within last 24 months plus at least 1 GdE
lesion


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ACTRIMS-ECTRIMS 2014
RADIANCE Phase 2 Trial Design
24-Week Placebo-Controlled
Treatment  Period
30-day
Screening
Period
7-day
Titration
Period
Randomization
1 mg RPC1063
0.5 mg RPC1063
Placebo
Week
-4
0
1
4
8
12
16
20
24
Safety
Only
Baseline
Blinded Safety-
Extension
1 mg RPC1063
0.5 mg RPC1063
1 mg RPC1063
0.5 mg RPC1063
Yearly
2°
Efficacy Endpoints:
1.
Number of GdE lesions at Week 24
2.
Cumulative new or enlarging T2 lesions
3.
Annualized Relapse Rate (ARR)
MRI
1°Endpoint: GdE Lesions


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ACTRIMS-ECTRIMS 2014
Patient Disposition
Randomized (N=258)
Placebo (N=88)
RPC1063 0.5 mg (N=87)
RPC1063 1 mg (N=83)
Discontinued
3 (3.4%)
Adverse event
0
Lost to follow-up
1 (1.1%)
Protocol violation
0
Consent withdrawn
2 (2.3%)
Discontinued
2 (2.3%)
Adverse event
0
Lost to follow-up
0
Protocol violation
1 (1.1%)
Consent withdrawn
1 (1.1%)
Discontinued
1 (1.2%)
Adverse event
0
Lost to follow-up
0
Protocol violation
0
Consent withdrawn
1 (1.1%)
Completed
85 (96.6%)
Completed
85 (97.7%)
Completed
82 (98.8%)
Very high rate of study compliance and completion
Similar completion rates across the treatment groups


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ACTRIMS-ECTRIMS 2014
Patient Demographics and RMS Disease History
Demographics
Placebo
(N=88)
RPC1063 0.5 mg
(N=87)
RPC1063 1 mg
(N=83)
Female –
n (%)
62  (70.5)
60  (69.0)
59  (71.1)
Age (yrs)
39.0 (8.7)
38.1 (9.2)
38.4 (9.8)
RMS Disease History, mean (SD)
Years since MS diagnosis
4.6 (5.1)
2.8 (5.0)
3.6 (4.4)
EDSS Score at Baseline
2.85 (1.27)
2.94 (1.29)
2.86 (1.21)
Relapses, last 12 months
1.3 (0.6)
1.5 (1.2)
1.3 (0.7)
Relapses, last 24 months
1.8 (1.0)
2.0 (1.8)
1.9 (1.1)
Gd-Enhancing lesions at Baseline
1.4 (3.4)
0.9 (1.4)
1.3 (2.8)
Gd-Enhancing lesion free at Baseline, n (%)
62  (70.5)
53  (60.9)
52  (62.7)


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ACTRIMS-ECTRIMS 2014
Primary Endpoint: Cumulative Number of Total GdE
Lesions From Weeks 12 to 24
p < 0.0001
p < 0.0001
86% decrease
86% decrease
11.1
1.5
1.5
0
2
4
6
8
10
12
14
Treatment Group
Placebo (N=88)
RPC1063 0.5 mg (N=87)
RPC1063 1 mg (N=83)


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ACTRIMS-ECTRIMS 2014
Secondary Endpoint (1):
Mean Number of GdE Lesions at Week 24
p < 0.0001
p < 0.0001
91% decrease
94% decrease
3.2
0.3
0.2
0
0.5
1
1.5
2
2.5
3
3.5
Treatment Group
Placebo (N=88)
RPC1063 0.5 mg (N=87)
RPC1063 1 mg (N=83)


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ACTRIMS-ECTRIMS 2014
Secondary Endpoint (2): Cumulative Number of New
or Enlarging T2 Lesions From Weeks 12 to 24
p < 0.0001
p < 0.0001
84% decrease
91% decrease
9.0
1.4
0.8
0
2
4
6
8
10
12
Treatment Group
Placebo (N=88)
RPC1063 0.5 mg (N=87)
RPC1063 1 mg (N=83)


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ACTRIMS-ECTRIMS 2014
Secondary Endpoint (3):
Annualized Relapse Rate
p = 0.271
31% decrease
p = 0.053
53% decrease
0.5
0.35
0.24
0
0.1
0.2
0.3
0.4
0.5
0.6
Treatment Group
Placebo (N=88)
RPC1063 0.5 mg (N=87)
RPC1063 1 mg (N=83)


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ACTRIMS-ECTRIMS 2014
Pharmacodynamic Effect of RPC1063:
Mean ±
SE Percent Change in Absolute Lymphocyte Counts
0
4
12
24
Study Week
0
-20
-40
-60
50%
60%
Program: E:\SASData\rpc1063\201a\csr\prog\g_lymph.sas
08JUN2014
~
~


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ACTRIMS-ECTRIMS 2014
SAFETY:
Treatment Emergent Adverse Events, n (%)
(All 24-week Double blind phase)
Placebo
(N=88)
RPC1063 0.5 mg
(N=87)
RPC1063 1 mg
(N=83)
Number of subjects experiencing
1 TEAE
52 (59.1)
56 (64.4)
47 (56.6)
1 moderate or severe TEAE
23 (26.1)
24 (27.6)
13 (15.7)
1 severe TEAE
1  (1.1)
2  (2.3)
1  (1.2)
1 possible, probable, or related TEAE
11 (12.5)
19 (21.8)
15 (18.1)
1 related TEAE
1  (1.1)
1  (1.1)
0
Preferred Term
Placebo
(N=88)
RPC1063 0.5 mg
(N=87)
RPC1063 1 mg
(N=83)
Nasopharyngitis
12 (13.6%)
11 (12.6%)
5 (6.0%)
Headache
8 (9.1%)
5 (5.7%)
3 (3.6%)
Urinary Tract Infection
2 (2.3%)
6 (6.9%)
2 (2.4%)
Most Common TEAEs  in RPC1063-treated Patients


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ACTRIMS-ECTRIMS 2014
SAFETY: Serious TEAEs
Only 3 Serious TEAEs (reported as unrelated) during the study
*No change in EDSS post IV methyprednisolone treatment; did not qualify as a protocol-defined
relapse but was considered related to the patient’s MS
Preferred Term
Placebo
(N=88)
n (%)
RPC1063
0.5 mg
(N=87)
n (%)
RPC1063
1 mg
(N=83)
n (%)
Total number of Serious TEAEs
0
3
0
Number
of Subjects with
1 Serious TEAE
0
3  (3.4)
0
Optic
neuritis*
0
1
(1.1)
0
Somatoform autonomic
dysfunction
0
1  (1.1)
0
Uterine
cervical squamous metaplasia
0
1  (1.1)
0


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ACTRIMS-ECTRIMS 2014
SAFETY: Non-Serious TEAEs
No notable cardiac, pulmonary, ophthalmologic, infectious
or malignancy TEAEs were observed
3 TEAEs
of
elevated
liver
enzymes
(
3x
ULN)
without
clinical signs/symptoms were observed
All were isolated ALT elevations (without AST or Bilirubin elevations)
None
5x ULN
Transient elevations despite continued treatment
Parameter
Placebo
(N=87)
RPC1063 0.5 mg
(N=85)
RPC1063 1 mg
(N=83)
Alanine Aminotransferase (ALT)
3x ULN, n (%)
0
2 (2.4%)
1 (1.2%)
Aspartate Aminotransferase (AST)
3x ULN, n (%)
0
0
0


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ACTRIMS-ECTRIMS 2014
Placebo
(N=88)
RPC1063 0.25 mg
(N=170)
Subjects with 2
nd
Degree AVB, type I
2 (2.3%)
4 (2.4%)
Subjects
with
Sinus
Pause
(
2
seconds)
1 (1.1%)
1 (0.6%)
Day 1: Cardiac Findings on 24-hr Holter
SYSTEM ORGAN CLASS
Preferred Term
Placebo
(N=88)
RPC1063 0.5 mg
(N=87)
RPC1063 1 mg
(N=83)
CARDIAC DISORDERS
2  (2.3%)
2  (2.3%)
1  (1.2%)
Angina Pectoris
0
0
1  (1.2%)
First Degree AV Block
1  (1.1%)
0
0
Palpitations
1  (1.1%)
2  (2.3%)
0
Overall Incidence of Cardiac TEAEs
Cardiac Safety Profile of RPC1063


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ACTRIMS-ECTRIMS 2014
Conclusions
Both doses of RPC1063 demonstrated large,
significant and consistent reductions of all MRI
measures of MS disease activity
The overall tolerability and safety profile of RPC1063,
including cardiac and hepatic safety results, suggests
a favorable risk-benefit profile in the treatment of RMS
These results support the ongoing Phase 3 portion of
the RADIANCE trial and the second Phase 3 trial of
RPC1063 vs. IFN
-1a in RMS (SUNBEAM)