UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): December 9, 2016
Biogen Inc.
(Exact name of registrant as specified in its charter)
Delaware | 0-19311 | 33-0112644 |
(State or other jurisdiction of incorporation) | (Commission File Number) | (IRS Employer Identification No.) |
225 Binney Street, Cambridge, Massachusetts 02142
(Address of principal executive offices; Zip Code)
Registrant’s telephone number, including area code: (617) 679-2000
Not Applicable
(Former name or former address, if changed since last report.)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Item 7.01 Regulation FD Disclosure
Attached as Exhibit 99.1 and Exhibit 99.2 to this Current Report on Form 8-K are slides from presentations that Biogen Inc. made on December 9, 2016 at the 9th Clinical Trials on Alzheimer's Disease (CTAD) meeting in San Diego, California.
Limitation on Incorporation by Reference. The information furnished in this Item 7.01 shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall such information be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act except as expressly set forth by specific reference in such a filing.
Cautionary Note Regarding Forward-Looking Statements. The presentations may contain forward-looking statements, including statements about additional results from the Phase 1b study, and the potential clinical effects and safety of aducanumab. These statements may be identified by words such as "believe," "expect," "may," "plan," "potential," "will" and similar expressions, and are based on our current beliefs and expectations. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. Factors which could cause actual results to differ materially from our current expectations include the risk that we may not fully enroll our clinical trials or enrollment will take longer than expected, unexpected concerns may arise from additional data, analysis or results obtained during our clinical trials, regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of our drug candidates, or we may encounter other unexpected hurdles. For more detailed information on the risks and uncertainties associated with our drug development and commercialization activities, please review the Risk Factors section of our most recent annual or quarterly report filed with the Securities and Exchange Commission. Any forward-looking statements speak only as of the date of the presentations and we assume no obligation to update any forward-looking statements.
Item 9.01 Financial Statements and Exhibits
Exhibit No. | Description |
99.1 | Aducanumab Titration Dosing Regimen Presentation slides from CTAD dated December 9, 2016 |
99.2 | Aducanumab 24 Month Data from Prime Presentation slides from CTAD dated December 9, 2016 |
Signatures
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
Biogen Inc.
By: __/s/ Steven N. Avruch_________
Steven N. Avruch
Chief Corporation Counsel and Assistant Secretary
Date: December 9, 2016
EXHIBIT INDEX
Exhibit Number | Description |
99.1 | Aducanumab Titration Dosing Regimen Presentation slides from CTAD dated December 9, 2016 |
99.2 | Aducanumab 24 Month Data from Prime Presentation slides from CTAD dated December 9, 2016 |
Interim analysis presented at CTAD 2016
Aducanumab Titration Dosing Regimen:
12-Month Interim Analysis from PRIME,
a Randomized, Double-Blind, Placebo-Controlled
Phase 1b Study in Patients With Prodromal or
Mild Alzheimer’s Disease
Vissia Viglietta,1 John O’Gorman,1 Leslie Williams,1 Tianle Chen,1
Ahmed Enayetallah,1 Ping Chiao,1 Christoph Hock,2 Roger M. Nitsch,2
Samantha Budd Haeberlein,1 Alfred Sandrock1
1Biogen, Cambridge, MA, USA; 2Neurimmune, Schlieren-Zurich, and University of Zurich, Switzerland
Interim analysis presented at CTAD 2016
Disclosures
This study is funded by Biogena
VV, JO, LW, TC, AE, PC, SBH, and AS are employees and
shareholders of Biogen
CH and RMN are employees and shareholders of Neurimmune
aMedical writing support for this presentation was provided by Erin Bekes, PhD, of Complete Medical Communications and funded by Biogen.
Interim analysis presented at CTAD 2016
Introduction
Aducanumab is a human monoclonal antibody selective for aggregated
forms of Aβ, including soluble oligomers and insoluble fibrils
PRIME is an ongoing Phase 1b study assessing the safety, tolerability, PK
and PD of aducanumab in patients with prodromal or mild Alzheimer’s
disease
Results from a 12-month interim analysis from fixed-dose cohorts have been
previously published1
Here we present 12-month interim data for both fixed-dose and titrated
aducanumab in PRIME
1. Sevigny et al. Nature 2016;537:50-56
PD, pharmacodynamics; PK, pharmacokinetics
Interim analysis presented at CTAD 2016
1 mg/kg
3 mg/kg
Placebo
Titration (ApoE ε4 carriers)
Placebo (ApoE ε4 carriers)
6 mg/kg
Placebo
PRIME Study Design:
Placebo-Controlled and LTE Periods
Randomization: 3:1 active: placebo within cohorts, fixed-dose cohorts stratified by ApoE ε4 status
Planned sample size: 188 patients
Titration cohort of ApoE ε4 carriers added after enrollment into fixed-dose arms was complete (planned sample size: 21
aducanumab: 7 placebo)
CDR–SB, Clinical Dementia Rating‒Sum of Boxes; LTE, long-term extension; MMSE, Mini-Mental State Examination; PET, positron emission
tomography
10 mg/kg
Placebo
36-Month
LTE
Prodromal or mild
AD
MMSE ≥20
Stable
concomitant
medications
Positive amyloid
PET scan
Population
Staggered Parallel-Group Design
Primary endpoint:
safety and
tolerability
Secondary
endpoints: serum
PK,
immunogenicity,
change in amyloid
PET (Week 26)
Exploratory
endpoints included
CDR–SB, MMSE,
change in amyloid
PET (Week 54)
Endpoints
12-Month
Placebo-Controlled Period
Interim analysis presented at CTAD 2016
Titration Dosing Regimen
in the 12-Month Placebo-Controlled Period
3 mg/kg 6 mg/kg 10 mg/kg
Study
week: 0 4 8 12 16 20 24 28 32 36 40 44 48 52
Dose
(mg/kg):
Placebo
1 1 3 3 3 3 6 6 6 6 6 10 10 10
1 mg/kg
By Week 52
average expected
dose
= 5.3 mg/kg
By Week 24
average expected
dose
= 2.9 mg/kg
Interim analysis presented at CTAD 2016
Patient Disposition at 12 Months
AE, adverse event
Analysis of data from all cohorts up to Week 54
Randomized
Dosed
Discontinued treatment
AE
Lost to follow-up
Disease progression
Consent withdrawn
Investigator decision
Death
Other
197
randomized
(by cohort)
1 mg/kg
31
Pooled
placebo
48
3 mg/kg
33
6 mg/kg
30
10 mg/kg
32
31 48 32 30 32
7
3
0
0
2
0
0
2
10
3
0
0
0
1
1
5
6
2
1
0
1
0
0
2
5
3
0
1
1
0
0
0
12
10
0
0
1
1
0
0
Titration
23
23
4
2
0
0
0
0
0
2
Interim analysis presented at CTAD 2016
Baseline Disease Characteristics
AD, Alzheimer’s disease; SD, standard deviation; SUVR, standardized uptake value ratio
aCholinesterase inhibitors and/or memantine.
Aducanumab
Placebo
(n=48)
1 mg/kg
(n=31)
3 mg/kg
(n=32)
6 mg/kg
(n=30)
10 mg/kg
(n=32)
Titration
(n=23)
Age in years, mean ± SD 73.3 ± 6.8 72.6 ± 7.8 70.5 ± 8.2 73.3 ± 9.3 73.7 ± 8.3 73.1 ± 7.8
ApoE ε4, n (%)
Carriers
Non-carriers
34 (71)
14 (29)
19 (61)
12 (39)
21 (66)
11 (34)
21 (70)
9 (30)
20 (63)
12 (38)
23 (100)
0
Clinical stage, n (%)
Prodromal
Mild
22 (46)
26 (54)
10 (32)
21 (68)
14 (44)
18 (56)
12 (40)
18 (60)
13 (41)
19 (59)
13 (57)
10 (43)
MMSE, mean ± SD 24.7 ± 3.6 23.6 ± 3.3 23.2 ± 4.2 24.4 ± 2.9 24.8 ± 3.1 24.7 ± 3.0
CDR Global Score, n (%)
0.5
1
40 (83)
8 (17)
22 (71)
9 (29)
22 (69)
10 (31)
25 (83)
5 (17)
24 (75)
8 (25)
18 (78)
5 (22)
CDR-SB, mean ± SD 2.69 ± 1.54 3.40 ± 1.76 3.50 ± 2.06 3.32 ± 1.54 3.14 ± 1.71 3.24 ± 1.84
PET SUVR, mean composite 1.435 1.441 1.464 1.429 1.441 1.325
AD medications used,a n (%) 30 (63) 21 (68) 28 (88) 20 (67) 17 (53) 12 (52)
Interim analysis presented at CTAD 2016
PET AMYLOID IMAGING
Interim analysis presented at CTAD 2016
Aducanumab Reduces Amyloid Plaques
Nominal p values: * P<0.05; **P<0.01; ***P<0.001 vs placebo.
1. Ostrowitzki et al. Arch Neurol 2012
Analyses based on observed data. ANCOVA for change from baseline with factors of treatment, laboratory ApoE ε4 status (carrier and non-carrier), and baseline composite
SUVR. PD analysis population is defined as all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline assessment of the
parameter. ANCOVA, analysis of covariance; SE, standard error
Adu
c
anu
m
a
b
Interim analysis presented at CTAD 2016
CLINICAL ENDPOINTS
Interim analysis presented at CTAD 2016
Effect of Aducanumab on Clinical Decline
as Measured by CDR–SB (exploratory endpoint)
CDR-SB is an exploratory endpoint. Analyses based on observed data. ANCOVA for change from baseline with factors of treatment, laboratory
ApoE ε4 status (carrier and non-carrier), and baseline CDR-SB. Efficacy analysis population is defined as all randomized subjects who received
at least 1 dose of study medication and had at least 1 post-baseline questionnaire assessment
Aducanu
m
a
b
*Nominal
P<0.05 vs
placebo
Difference
from placebo
at Week 54
-0.20
-0.56
-1.26
-0.80
*
Interim analysis presented at CTAD 2016
Effect of Aducanumab on Clinical Decline
as Measured by MMSE (exploratory endpoint)
MMSE is an exploratory endpoint. Analyses based on observed data. ANCOVA for change from baseline with factors of treatment, laboratory ApoE ε4 status
(carrier and non-carrier), and baseline MMSE. Efficacy analysis population is defined as all randomized patients who received at least 1 dose of study
medication and had at least 1 post-baseline questionnaire assessment.
*Nominal
P<0.05 vs
placebo
Difference
from placebo
at Week 52
1.91
1.70
0.25
0.47
*
Interim analysis presented at CTAD 2016
SAFETY AND
TOLERABILITY
Interim analysis presented at CTAD 2016
No New Safety Signals Identified in Titration Cohort
During 12-Month Placebo-Controlled Period
No new safety signals were identified in the titration cohort
As previously presented for the fixed-dose cohorts:
- The most common AE/SAE was ARIA
- Other AEs/SAEs were consistent with the patient population
• Three deaths; none considered treatment-related; two in placebo and one in 10 mg/kg arm
(two occurred after study discontinuation)
- No significant changes in chemistry, hematology, urinalysis, ECGs, or vital signs
ARIA, amyloid-related imaging abnormalities; ECG, electrocardiogram; SAE, serious adverse event
Aducanumab
Placebo
(N=48)
1 mg/kg
(N=31)
3 mg/kg
(N=32)
6 mg/kg
(N=30)
10 mg/kg
(N=32)
Titration
(N=23)
Number with an AE (%) 47 (98) 28 (90) 27 (84) 28 (93) 29 (91) 21 (91)
Number with an SAE (%) 16 (33) 4 (13) 4 (13) 4 (13) 12 (38) 5 (22)
Number discontinuing
treatment due to AE (%)
4 (8) 3 (10) 2 (6) 3 (10) 10 (31) 2 (9)
Interim analysis presented at CTAD 2016
Dose Titration Slightly Attenuated Incidence of
ARIA-E Versus Higher Fixed Doses
Incidence of ARIA based on MRI.
ARIA-E, ARIA‒vasogenic edema; ARIA-H, ARIA‒microhemorrhages, macrohemorrhages, or superficial siderosis; MRI, magnetic resonance
imaging
Placebo
Aducanumab
1 mg/kg 3 mg/kg 6 mg/kg 10 mg/kg Titration
Patients with at least 1
post-baseline MRI
46 31 32 30 32 23
ARIA-E,a n (%) 0/46 1/31 (3) 2/32 (6) 11/30 (37) 13/32 (41) 8/23 (35)
aARIA-E with or without ARIA-H.
ApoE ε4 carrier 0/32 1/19 (5) 1/21 (5) 9/21 (43) 11/20 (55) 8/23 (35)
ApoE ε4 non-carrier 0/14 0/12 1/11 (9) 2/9 (22) 2/12 (17) --
Isolated ARIA-H, n (%) 3/46 (7) 2/31 (6) 3/32 (9) 0/30 2/32 (6) 0/23
Interim analysis presented at CTAD 2016
Timing of ARIA-E in the Titration Cohort
8 subjects had ARIA-E in 3 or 6 mg/kg stage.
13 subjects reached 10 mg/kg without ARIA-E
- Currently 12 of the 13 subjects are active in the study
• All 12 have received ≥10 doses of 10 mg/kg
1 1 3 3 3 3 6 6 6 6 6 10 10 10
Study
week 0 4 8 12 16 20 24 28 32 36 40 44 48 52
Dose
Placebo-Controlled Period LTE Period
10
56
10
60
10
64
10
68
10
72
10
76
10
80
MRI
=ARIA-E cases
Interim analysis presented at CTAD 2016
Most Titration Patients with ARIA-E
Continued Treatment
Among ApoE ε4 carriers with ARIA-E,
4/11 (36%) in the 10 mg/kg group continued treatment
7/9 (78%) in the 6 mg/kg group continued treatment
6/8 (75%) in the titration group continued treatment
Aducanumab
1 mg/kg 3 mg/kg 6 mg/kg 10 mg/kg Titration
ApoE ε4 carriers with at least 1
post-baseline MRI
19 21 21 20 23
ARIA-E, n (%) 1 (5) 1 (5) 9 (43) 11 (55) 8 (35)
Continued treatment, n (%) 0 1 (5) 7 (33) 4 (20) 6 (26)
Same dose 0 0 1 0 0
Reduced dose 0 1 6 4 6
Discontinued treatment, n (%) 1 (5) 0 2 (10) 7 (35) 2 (9)
Interim analysis presented at CTAD 2016
ARIA-E Characteristics in the Titration Cohort
Majority of cases occurred within the first 5 months of
treatment
75% of events were asymptomatic
2 patients (25%) had mild symptoms that resolved
MRI findings typically resolved within 412 weeks
Interim analysis presented at CTAD 2016
Summary
Both titration and fixed doses of aducanumab significantly reduced amyloid plaque
burden following 12 months of treatment versus placebo
Clinical effects with titrated aducanumab were generally consistent with findings in the
fixed-dose cohorts
- Slowing of decline as measured by the CDR–SB and MMSE was observed in the
titration and fixed-dose cohorts
Titration up to 10 mg/kg may reduce incidence of ARIA-E compared with higher fixed
dosing based on the ApoE ε4 cohort studied
PRIME results support the study design of the ENGAGE and EMERGE Phase 3 trials,
which are investigating the clinical efficacy and safety of aducanumab in patients with
early AD
24-month data with fixed doses of aducanumab from PRIME will also be presented at
CTAD 2016 (Fri Dec 9, 9:15 AM)
Interim analysis presented at CTAD 2016
Acknowledgments
We thank all the patients and their family
members participating in the aducanumab
studies, as well as the investigators and their staff
conducting these studies.
Interim analysis presented at CTAD 2016
Aducanumab 24-Month Data From PRIME: A Randomized
Double-Blind, Placebo-Controlled Phase 1b Study in
Patients With Prodromal or Mild Alzheimer’s Disease
Vissia Viglietta,1 John O’Gorman,1 Leslie Williams,1 Tianle Chen,1
Ahmed Enayetallah,1 Ping Chiao,1 Christoph Hock,2 Roger M. Nitsch,2
Samantha Budd Haeberlein,1 Alfred Sandrock1
1Biogen, Cambridge, MA, USA; 2Neurimmune, Schlieren-Zurich, and University of Zurich, Switzerland
Interim analysis presented at CTAD 2016
Disclosures
This study was funded by Biogena
VV, JO, LW, TC, AE, PC, SBH, and AS are employees and
shareholders of Biogen
CH and RMN are employees and shareholders of Neurimmune
aMedical writing support for this presentation was provided by Erin Bekes, PhD, of Complete Medical Communications and funded by Biogen.
Interim analysis presented at CTAD 2016
Overview
Aducanumab is a human monoclonal antibody selective for aggregated
forms of Aβ, including soluble oligomers and insoluble fibrils
PRIME is an ongoing Phase 1b study assessing the safety, tolerability, PK
and PD of aducanumab in patients with prodromal or mild Alzheimer’s
disease
Here we present 24-month data from the 12-month placebo-controlled period
and the first 12 months of the LTE period of PRIME
- Data from the titration cohort are not reported because 24-month data are not yet
available for this cohort
Primary endpoint in the LTE was safety/tolerability
Exploratory endpoints included:
• Changes in amyloid PET
• Measures of clinical decline on the CDR–SB and MMSE
CDR-SB, Clinical Dementia Rating-Sum of Boxes; MMSE, Mini-Mental State Examination; PD, pharmacodynamics; PET, positron emission
tomography; PK, pharmacokinetics; LTE, long-term extension
Interim analysis presented at CTAD 2016
• Randomization: 3:1 active: placebo within cohorts, fixed-dose cohorts stratified by ApoE ε4 status
• Patients randomized to placebo or aducanumab 1 mg/kg in the placebo-controlled period were switched to aducanumab
3 mg/kg or titration in the LTE (“switchers”). Patients randomized to aducanumab 3, 6, or 10 mg/kg or titration in the
placebo-controlled period were assigned to continue in the same dose group in the LTE (“continuers”)
PRIME Study Design:
Placebo-Controlled and LTE Periods
aData from the titration cohort are not included in this analysis as 24-month data from this cohort are not yet available. bFor patients switched
from placebo to titration in the LTE, titration denotes 2 doses of 3 mg/kg followed by subsequent doses of 6 mg/kg.
1 mg/kg
3 mg/kg
Placebo
Titration (ApoE ε4 carriers; 1→10 mg/kg)a
Placebo (ApoE ε4 carriers)a
6 mg/kg
Placebo
Placebo-controlled period
10 mg/kg
Placebo
LTE period
All patients receive aducanumab
3 mg/kg
Aducanumab 3 mg/kg or titration (3→6 mg/kg)b
Aducanumab titration (ApoE ε4 carriers;
1→10 mg/kg)a
Aducanumab titration (3→6 mg/kg)b
3 mg/kg
Titration (ApoE ε4 carriers; 1→10 mg/kg)a
6 mg/kg
10 mg/kg
Aducanumab titration (3→6 mg/kg)b
Interim analysis presented at CTAD 2016
Timeline of Dose Administration and
Key Assessments in PRIME
aSchedule of brain MRIs for fixed-dose cohorts (Arms 1-7)
MRI, magnetic resonance imaging
IV infusions every 4 weeks over 52 weeks (14 total)
active or placebo
IV infusions every 4 weeks over a total of 3 years
All patients received active treatment
6 52-5418 30 42
LTE
Years 2-3Screening
62 70 76-78 90 102 108-110
Placebo controlled period
Week
MRIa
Amyloid
PET
Clinical
Tests
LTE (Year 1)
24-26
Interim analysis presented at CTAD 2016
Dosed in placebo-controlled
period
Completed treatment in the
placebo-controlled period
166 randomized
(165 dosed)
1 mg/kg
31
Pooled
placebo
40
3 mg/kg
32
6 mg/kg
30
10 mg/kg
32
2430 26 25 20
Patient Disposition at 24 Months
Analysis of data from fixed-dose arms up to Month 24.
Discontinued treatment
in the first year of the LTE
AE
Other
Death
Disease progression
4
0
4
0
0
8
7
0
0
1
8
2
6
0
0
2
0
1
1
0
4
3
1
0
0
Dosed in the LTE 1929 26 24 19
Switchers Continuers
Interim analysis presented at CTAD 2016
Baseline Disease Characteristics:
Placebo-Controlled Period
SUVR, standardized uptake value ratio
aCholinesterase inhibitors and/or memantine
Placebo
(n=40)
Aducanumab
1 mg/kg
(n=31)
3 mg/kg
(n=32)
6 mg/kg
(n=30)
10 mg/kg
(n=32)
ApoE ε4, n (%)
Carriers
Non-carriers
26 (65)
14 (35)
19 (61)
12 (39)
21 (66)
11 (34)
21 (70)
9 (30)
20 (63)
12 (38)
Clinical stage, n (%)
Prodromal
Mild
19 (48)
21 (53)
10 (32)
21 (68)
14 (44)
18 (56)
12 (40)
18 (60)
13 (41)
19 (59)
MMSE, mean ± SD 24.7 ± 3.6 23.6 ± 3.3 23.2 ± 4.2 24.4 ± 2.9 24.8 ± 3.1
CDR Global Score, n (%)
0.5
1
34 (85)
6 (15)
22 (71)
9 (29)
22 (69)
10 (31)
25 (83)
5 (17)
24 (75)
8 (25)
Age years, mean ± SD 72.8 ± 7.2 72.6 ± 7.8 70.5 ± 8.2 73.3 ± 9.3 73.7 ± 8.3
CDR-SB, mean ± SD 2.66 ± 1.50 3.40 ± 1.76 3.50 ± 2.06 3.32 ± 1.54 3.14 ± 1.71
PET SUVR, mean composite 1.441 1.441 1.464 1.429 1.441
AD medications use,a n (%) 24 (60) 21 (68) 28 (88) 20 (67) 17 (53)
Interim analysis presented at CTAD 2016
PET AMYLOID IMAGING
-0.40
-0.30
-0.20
-0.10
0.00
0.10
Aducanumab Reduced Amyloid Plaque Burden
Over 24 Months
** Nominal P<0.01; *** Nominal P<0.001 vs placebo in the placebo-controlled period and vs placebo switchers in the LTE period.
Results based on MMRM, fitted with change from baseline as a dependent variable, and included fixed effects for categorical treatment, categorical visit and treatment-by-visit
interaction, continuous baseline value, and laboratory ApoE ε4 status (carrier and non-carrier).
MMRM, mixed model for repeated measures
A
d
j
u
s
t
e
d
m
e
a
n
c
h
a
n
g
e
f
r
o
m
b
a
s
e
l
i
n
e
(
±
S
E
)
Placebo-controlled period LTE period
(all patients received aducanumab)
Weeks 0 26 54 110
Placebo n=34 34 30 3 or 3→6 mg/kg 18
1 mg kg n=26 26 21 3 mg/kg 13
3 mg/kg n=29 27 26 18
6 mg/kg n=24 23 23 18
10 mg/kg n=28 27 21 13
A
d
u
c
a
n
u
m
a
b
Analysis visit (weeks)
110
Difference
from placebo
switchers at
Week 110
0.007
54260
***
**
***
******
***
**
***
-0.038
-0.167
-0.122
Placebo switchers
Continuers
Interim analysis presented at CTAD 2016
CLINICAL ENDPOINTS
Interim analysis presented at CTAD 2016
0.00
0.50
1.00
1.50
2.00
2.50
3.00
3.50
4.00
4.50
Continued Slowing of Decline on CDR-SB
Over 24 Months
CDR‒SB is an exploratory endpoint. Results based on MMRM, fitted with change from baseline as a dependent variable, and included fixed effects for categorical treatment,
categorical visit and treatment-by-visit interaction, continuous baseline value, and laboratory ApoE ε4 status (carrier and non-carrier). MMRM, mixed model for repeated
measures.
Placebo-controlled period LTE period
(all patients received aducanumab)
A
d
j
u
s
t
e
d
m
e
a
n
c
h
a
n
g
e
f
r
o
m
b
a
s
e
l
i
n
e
(
±
S
E
)
Analysis visit (weeks)
Weeks 0 26 54 78 110
Placebo n=36 36 31 3 or 3→6 mg/kg 23 21
1 mg kg n=28 28 23 3 mg/kg 15 14
3 mg/kg n=30 30 27 21 16
6 mg/kg n=27 27 26 24 23
10 mg/kg n=28 28 23 14 15A d
u
c
a
n
u
m
a
b
Difference
from placebo
switchers at
Week 110
0.21
-0.97
-1.62
-0.29
11054260 78
Interim analysis presented at CTAD 2016
-7
-6
-5
-4
-3
-2
-1
0
1
Continued Slowing of Decline on MMSE
Over 24 Months
*Nominal P<0.05 (vs placebo [Week 52] or placebo switchers [Weeks 76 and 108])
MMSE is an exploratory endpoint. Results based on MMRM, fitted with change from baseline as a dependent variable, and included fixed effects for categorical treatment,
categorical visit and treatment-by-visit interaction, continuous baseline value, and laboratory ApoE ε4 status (carrier and non-carrier). MMRM, mixed model for repeated
measures.
Analysis visit (weeks)
A
d
j
u
s
t
e
d
m
e
a
n
c
h
a
n
g
e
f
r
o
m
b
a
s
e
l
i
n
e
(
±
S
E
)
Placebo-controlled period LTE period
(all patients received aducanumab)
Weeks 0 24 52 76 108
Placebo n=37 36 32 3 or 3→6 mg/kg 24 21
1 mg kg n=26 26 25 3 mg/kg 15 15
3 mg/kg n=29 29 26 21 17
6 mg/kg n=28 28 26 24 23
10 mg/kg n=30 29 25 14 15A d
u
c
a
n
u
m
a
b
10854260 78
*
Difference
from placebo
switchers at
Week 108
1.65
2.47
3.27
0.06
*
*
Interim analysis presented at CTAD 2016
SAFETY AND
TOLERABILITY
Interim analysis presented at CTAD 2016
Continuersb
3 mg/kg
(N=26)
6 mg/kg
(N=24)
10 mg/kg
(N=19)
Number with an AE (%) 18 (69) 22 (92) 15 (79)
Number with an SAE
(%) 2 (8) 6 (25) 3 (16)
Number discontinuing
treatment due to AE (%) 2 (8) 0 3 (16)
No New Safety Signals Identified
with Aducanumab in the First Year of the LTE
aPlacebo switchers received aducanumab 3 mg/kg or titration (2 doses of 3 mg/kg followed by subsequent doses of 6 mg/kg) in the LTE. bPatients who were
randomized to receive 3, 6, and 10 mg/kg were scheduled to receive the same dose throughout the LTE. Patients who received a dose reduction during the
placebo-controlled period due to ARIA would remain on the reduced dose throughout the LTE. cBased on incidence reporting by preferred term.
AE, adverse event; ARIA, amyloid-related imaging abnormality; SAE, serious AE
The most common AEs in the LTE were fall, headache, and ARIAc
Treatment-related SAEs occurring in 2 or more patients in the LTE were ARIAc (n=5),
including one subject with a concurrent SAE of seizure and loss of pulse
- Other AEs/SAEs were consistent with the patient population
- There were two deaths (none considered treatment-related), one in the 6 mg/kg
arm and one in the 10 mg/kg arm, in the first year of the LTE (one occurred after
study discontinuation)
Placebo
Switchersa
(N=29)
1 mg/kg →
3 mg/kg
(N=19)
27 (93) 15 (79)
13 (45) 2 (11)
7 (24) 0
Interim analysis presented at CTAD 2016
Patients with ≥1 post-
baseline MRI
ARIA-E,a n (%)
ApoE ε4 carrier
ApoE ε4 non-carrier
Isolated ARIA-H, n (%)
No Continuers Developed ARIA-E
During the First Year of the LTE
bPatients who were randomized to receive 3, 6, and 10 mg/kg were scheduled to receive the same dose throughout the LTE. Patients who received a dose
reduction during the placebo-controlled period due to ARIA would remain on the reduced dose throughout the LTE. cPlacebo switchers received aducanumab 3
mg/kg or titration (2 doses of 3 mg/kg followed by subsequent doses of 6 mg/kg) in the LTE.
ARIA-E, ARIA‒vasogenic edema; ARIA-H, ARIA‒microhemorrhages, macrohemorrhages, or superficial siderosis
No new ARIA-E cases or recurrence were observed among aducanumab
continuers
Continuersb
3 mg/kg 6 mg/kg 10 mg/kg
23 24 19
0/23 0/24 0/19
0/16 0/17 0/12
0/7 0/7 0/7
3/23 (13) 2/24 (8) 1/19 (5)
aARIA-E with or without ARIA-H
Placebo
Switchersc
1 mg/kg →
3 mg/kg
29 17
5/29 (17) 3/17 (18)
4/17 (24) 3/11 (27)
1/12 (8) 0/6
2/29 (7) 0/17
Interim analysis presented at CTAD 2016
Patients with ≥1 post-
baseline MRI
ARIA-Ea, n (%)
Continued treatment, n
(%)
Same dose
Reduced dose
Discontinued treatment, n
(%) 0 0 0
ApoE ε4 carriers 3 0 0 0 0
ApoE ε4 non-carriers 1 0 0 0 0
Discontinuations due to ARIA-E
During the First Year of the LTE
bPatients who were randomized to receive 3, 6, and 10 mg/kg were scheduled to receive the same dose throughout the LTE. Patients who received a dose
reduction during the placebo-controlled period due to ARIA would remain on the reduced dose throughout the LTE. cPlacebo switchers received aducanumab 3
mg/kg or titration (2 doses of 3 mg/kg followed by subsequent doses of 6 mg/kg) in the LTE.
Continuersb
3 mg/kg 6 mg/kg 10 mg/kg
23 24 19
0 0 0
0 0 0
0 0 0
0 0 0
aARIA-E with or without ARIA-H
Placebo
Switchersc
1 mg/kg →
3 mg/kg
29 17
5 (17) 3 (18)
1 ( 3) 3 (18)
0 2
1 1
4 (14) 0
Interim analysis presented at CTAD 2016
Summary
At 24 months, brain amyloid plaque burden continued to decrease in
aducanumab continuers
- This decrease was dose- and time-dependent
CDR‒SB and MMSE data suggest a clinical benefit in patients continuing
aducanumab over 24 months
No new ARIA-E cases or recurrence among aducanumab continuers
- ARIA-E incidence in aducanumab switchers was consistent with that
observed in the placebo-controlled portion of the study
These data continue to support further investigation of the clinical efficacy
and safety of aducanumab in patients with early AD in the ENGAGE and
EMERGE Phase 3 trials
Interim analysis presented at CTAD 2016
Acknowledgements
We thank all the patients and their family
members participating in the aducanumab studies
and the investigators and their staff conducting
these studies.