Download AHA Scientific Sessions 2014 Conference Call

AHA Scientific Sessions 2014
Conference Call
Scott Wasserman MD FACC
Executive Medical Director, Global Development
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
1
Safe Harbor Statement
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uncertainties and assumptions that could cause actual results to differ materially from those described. All statements, other than statements of historical fact, are
statements that could be deemed forward-looking statements, including statements about estimates of revenues, operating margins, capital expenditures, cash,
other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement
activities and outcomes and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed
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the uncertainties and risk factors related to our business. Unless otherwise noted, Amgen is providing this information as of November 18, 2014 and expressly
disclaims any duty to update information contained in this presentation.
No forward-looking statement can be guaranteed and actual results may differ materially from those we project. The Company’s results may be affected by our
ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments (domestic or foreign) involving
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successful. Cost saving initiatives may result in us incurring impairment or other related charges on our assets. We may experience difficulties, delays or
unexpected costs and not achieve anticipated benefits and savings from our recently announced restructuring plans. Our business performance could affect or
limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock.
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
2
Amgen Cardiovascular: Three Innovative
Molecules to Address Unmet Need
Class
Indications
Phase of
Development
Evolocumab
Ivabradine
Omecamtiv
Mecarbil
PCSK9 inhibitor
If Channel inhibitor
Cardiac myosin
activator
Dyslipidemia
Chronic heart failure
Heart failure
Regulatory review
in US and EU
Priority review
in US
Phase 2b
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
3
Evolocumab Clinical Data at AHA 2014
•
Evaluation of the Relationship Between Evolocumab 140 mg Every Two Weeks and 420 mg Monthly
Dosing Regimens—Abstract 16270
•
Safety and Tolerability of Very Low LDL-C Levels in Patients Treated with 52 Weeks of Evolocumab
(AMG 145)—Abstract 16865
•
Effects of Evolocumab Treatment on Serum Adrenal and Gonadal Hormone Levels: Results from the
52-week, Phase 3, Double-blind, Randomized, Placebo-controlled Study (DESCARTES)—Abstract 17005
•
Trial Assessing Long-Term Use of PCSK9 Inhibition in Patients with Genetic LDL Disorders (TAUSSIG):
Efficacy and Safety in Patients with Homozygous Familial Hypercholesterolemia Receiving Lipid
Apheresis—Abstract 17016
•
Long-Term Reduction in Lipoprotein (a) With the PCSK9 Monoclonal Antibody Evolocumab (AMG 145):
A Pooled Analysis of 3278 Patients in Phase 2, 3, and Open Label Extension Studies—Abstract 15743
•
The Diagnosis of Heterozygous Familial Hypercholesterolemia: Genotype versus
Phenotype—Abstract 17368
•
Impact of Baseline PCSK9 Levels on the Efficacy of Evolocumab, a Monoclonal Antibody
Against PCSK9—Abstract 16196
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
4
Our Evolocumab Global Clinical Program Evaluates
LDL-C; Effect On Plaque Burden; CV Outcomes
Combination therapy
Monotherapy
Statin intolerant
HeFH
HoFH

Phase 2
(N = 406)
Phase 2
(N = 157)
Phase 2
(N = 167)
Phase 2/3
(N = 58)
Phase 2
(N = 629)
Long-term safety
and efficacy
Open-label extension

Phase 3
(N = 614)
Phase 3 Phase 3
(N = 307)
(N = 100)
Phase 3
(N = 329)

Phase 2
(N > 1,324)
Phase 3
(N = 1,896)
Phase 2/3
(N = 310)

Phase 3
(N = 901)
Phase 3
(N > 3,800)
Vascular imaging
Phase 3
(N = 950)
Secondary prevention
Phase 3
(N = 27,500)
LDL-C = low-density lipoprotein cholesterol; CV = cardiovascular
HeFH = heterozygous familial hypercholesterolemia; HoFH = homozygous familial hypercholesterolemia;  = completed
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
5
Evaluation of the Relationship Between
Evolocumab 140 mg Every Two Weeks
and 420 mg Monthly Dosing Regimens
Scott M. Wasserman,1 Michael J. Koren,2 Robert P. Giugliano,3 John P. Gibbs,1 Jason Legg,1
Maury G. Emery,1 Peter C. Haughney,1 Thomas Liu,1 Rob Scott,1 and Marc S. Sabatine3
1Amgen
Inc., Thousand Oaks, CA; 2Jacksonville Center for Clinical Research, Jacksonville, FL;
3TIMI Study Group, Brigham and Women’s Hospital, Boston, MA
Consistent Reduction of LDL-C by Evolocumab
Dosed at 140 mg Q2W and 420 mg QM
B
200
Calculated LDL-C (mg/dL)
Calculated LDL-C (mg/dL)
A
150
100
50
0
200
150
100
50
0
0
1 8
9
10
11
12
0
1 8
Placebo QM (n=26)
Evolocumab 70 mg Q2W (n=22)
Evolocumab 140 mg Q2W (n=26)
10
11
12
Study Week
Study Week
Placebo Q2W (n=28)
9
Study drug administration
Evolocumab 280 mg QM (n=19)
Evolocumab 420 mg QM (n=30)
Study drug administration
Evolocumab 140 mg Q2W and 420 mg QM reduced LDL-C from baseline by 64.5% and 63.5%, respectively
Q2W = every 2 weeks; QM = monthly; Mean (± SD) calculated LDL-C from week 8 to week 12 after (A) every 2 week and (B) monthly dosing regimens
(MENDEL and LAPLACE-TIMI 57 PKPD substudy population, n = 151)
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
7
Differences Between Evolocumab Doses In Mean
Percent Change From Baseline at Weeks 10 and 12
• Efficacy was similar between
140 mg Q2W and 420 mg QM
• Efficacy was variable
between:
– Evolocumab 70 mg Q2W
and 140 mg Q2W
– Evolocumab 280 mg Q2W
and 420 mg QM
Pooled MENDEL and LAPLACE-TIMI 57 population; Point estimate box sizes are relative to standard errors
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
8
Safety and Tolerability of Very Low
LDL-C Levels in Patients Treated with
52 Weeks of Evolocumab (AMG 145)
Michael J. Koren,1 Dirk Blom,2 Robert P. Giugliano,3 Erik Stroes,4 Ransi Somaratne,5 Andrew Lowy,5
Maria Laura Monsalvo,5 Hui-Chun Hsu,5 Scott M. Wasserman,5 Rob Scott,5 Marc S. Sabatine3
1Jacksonville
Center for Clinical Research, Jacksonville, FL; 2Division of Lipidology, Department of Medicine, University of
Cape Town, South Africa; 3TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital and Harvard
Medical School, Boston, MA; 4Department of Vascular Medicine Academic Medical Center, Amsterdam, The Netherlands;
5Amgen Inc., Thousand Oaks, CA
Comparable Safety and Tolerability In Patients Achieving Very
Low LDL-C vs Those Achieving Higher LDL-C at 52 Weeks
LDL-C ≥ 40 mg/dL
LDL-C < 25 mg/dL
LDL-C < 40 mg/dL
Evolocumab
(N = 644)a
Evolocumab
(N = 1,005)b
Evolocumab
(N = 462)
Controlc
(N = 725)
Total
(N = 1187)
Any AE
78
78
83
75
78
SAE
6
6
8
7
7
14
14
15
12
13
10
8
6
5
9
7
6
6
8
5
10
5
7
5
6
4
7
5
7
5
0.3
0.6
0.6
0.1
0.3
3 (0.5)
6 (0.6)
5 (1)
12 (2)
17 (1)
4
4
4
4
4
1
0.9
1
1
1
0.8
7
3
1
2
1
0.9
0
0.3
0.2
%
Most common AEs
Nasopharyngitis
Upper respiratory
tract infection
Back pain
Influenza
Arthralgia
Neurocognitive AEs
Mental impairment
Positively adjudicated
CV events, n (%)
Myalgia
Laboratory Parameters, %
CK > 5x ULN
ALT or AST > 3x
ULNd
Total bilirubin > 2x
ULNd
•
No cases of hemorrhagic stroke
occurred in patients reaching
very low LDL-C levels or
allocated to evolocumab
•
Neurocognitive AE rates did not
differ according to treatment
assignment or achieved LDL-C
•
Adjudicated cardiovascular
events trended favorably in the
evolocumab-treated cohort
•
Ongoing clinical outcomes
studies will provide further and
more definitive assessments of
the benefits and risks of
lowering LDL-C to very low
levels
AE = adverse event; SAE = serious adverse event; CK = creatine kinase; ULN = upper limit of normal; ALT = alanine aminotransferase; AST = aspartate aminotransferase; a3 additional patients received control—
nasopharyngitis occurred in 1 patient in the control group and an adjudicated CV event occurred in 1 patient in the control group. b7 additional patients received control—nasopharyngitis occurred in 1 patient in the control
group and an adjudicated CV event occurred in 1 patient in the control group. cOSLER-1: Standard of Care; DESCARTES: Placebo. dElevations not considered clinically significant by investigators.
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
10
Baseline Statin Use Did Not Affect AE Rates
LDL-C
< 25 mg/dL
LDL-C
< 40 mg/dL
Evolocumaba
Evolocumabb
Evolocumab
Controlc
Total
Intensive
Any AE, (%)
74
75
86
70
75
Non-Intensive
Any AE, (%)
80
80
82
79
80
None
Any AE, (%)
80
79
81
75
79
a3
LDL-C ≥ 40 mg/dL
additional patients received control—2 were on intensive statin therapy and 1 was on non-intensive statin therapy; b7 additional patients received control—4 were
on intensive statin therapy, 2 were on non-intensive statin therapy, and 1 was on no statin; cOSLER-1: Standard of Care; DESCARTES: Placebo
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
11
Effects of Evolocumab Treatment on Serum Adrenal
and Gonadal Hormone Levels: Results from a
52-Week, Phase 3, Double-Blind, Randomized,
Placebo-Controlled Study (DESCARTES)
Dirk Blom,1 C. Stephen Djedjos,2 Kate Tsirtsonis,3 Scott M. Wasserman,2 Rob Scott,2 Eli Roth4
1Division
of Lipidology, Department of Medicine, University of Cape Town, South Africa; 2Amgen Inc., Thousand Oaks, CA,
USA; 3Amgen, Uxbridge, UK; 4Sterling Research Group, Cincinnati, OH, USA
Monthly Evolocumab Did Not Adversely Affect
Steroid Hormone Metabolism
• No correlation between change in LDL-C and change
in cortisol from baseline
• Cortisol at week 52 increased slightly from baseline in
evolocumab treated patients with LDL-C < 25 mg/dL
or 40 mg/dL at any visit
• Cortisol:ACTH ratio showed no significant change from
baseline to week 52 in any group
• Gonadal steroids and gonadotropins showed no
significant changes from baseline to week 52
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
13
Trial Assessing Long-Term Use of PCSK9 Inhibition in
Patients with Genetic LDL Disorders (TAUSSIG):
Efficacy and Safety in Patients with Familial
Hypercholesterolemia Receiving Lipid Apheresis
Eric Bruckert1, Vladimir Blaha2, Evan A. Stein3, Frederick J. Raal4, Christopher Kurtz5, Narimon
Honarpour5, Feng Xu6, John Gibbs5, Scott M. Wasserman5, Rob Scott5, Patrick Couture7
1Hôspital
Pitié Salpêtrière, Assistance-Publique Hôpitaux de Paris, Paris, France; 2Charles University, Hradec Kralove, Czech Republic;
3Metabolic and Atherosclerosis Research Center, Cincinnati, OH, USA; 4Carbohydrate & Lipid Metabolism Research Unit, University
of Witwatersrand, Johannesburg, South Africa; 5Amgen Inc., Thousand Oaks, CA, USA; 6Formerly of Amgen; 7Centre Hospitalier
Universitaire de Québec, Quebec City, Canada
Evolocumab Reduced LDL-C and Frequency of
Apheresis In Patients With HoFH and Severe FH
n
Baseline LDL-C,
mean (range),
mg/dL
UC LDL-C at time
of change,* mean
(range), mg/dL
Change in UC
LDL-C,
mean (range), %
Patients stopping apheresis
2
155 (181–129)
30 (16–43)
-82 (-88 – -76)
Patients changing frequency to monthly
3
174 (136–250)
90 (46–115)
-39 (-82 – -15)
Patients stopping apheresis
4
179 (146–212)
36 (21–47)
-79 (-90 – -70)
Patients changing frequency to monthly
1
214
62
-71
HoFH
Severe FH
•
•
In the HoFH group, 5 of 34 patients (15%) stopped or reduced the frequency of apheresis
In the severe FH group, 5 of 16 patients (31%) stopped or reduced the frequency of apheresis
–
•
At Week 12, 10 patients (63%) had stopped apheresis or achieved pre-apheresis LDL-C of < 70 mg/dL
Serious adverse events occurred in 5 patients†
UC = ultracentrifugation; *Change or cessation; pre-apheresis UC LDL-C on the day of the last scheduled apheresis session (if apheresis was stopped) or on the day of the
last apheresis session at the frequency of every two weeks; †Included myocardial ischemia, AV fistula thrombosis, hematuria occurring after apheresis, and carotid artery
stenosis in a patient with known cerebrovascular disease in HoFH; angina pectoris in severe FH; FH = familial hypercholesterolemia
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
15
Our Evolocumab Global Clinical Program Evaluates
LDL-C; Effect On Plaque Burden; CV Outcomes
Combination therapy
Monotherapy
Statin intolerant
HeFH
HoFH

Phase 2
(N = 406)
Phase 2
(N = 157)
Phase 2
(N = 167)
Phase 2/3
(N = 58)
Phase 2
(N = 629)
Long-term safety
and efficacy
Open-label extension

Phase 3
(N = 614)
Phase 3 Phase 3
(N = 307)
(N = 100)
Phase 3
(N = 329)

Phase 2
(N > 1,324)
Phase 3
(N = 1,896)
Phase 2/3
(N = 310)

Phase 3
(N = 901)
Phase 3
(N > 3,800)
Vascular imaging
Phase 3
(N = 950)
Secondary prevention
Phase 3
(N = 27,500)
LDL-C = low-density lipoprotein cholesterol; CV = cardiovascular
HeFH = heterozygous familial hypercholesterolemia; HoFH = homozygous familial hypercholesterolemia;  = completed
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
16
Plaque Burden and LDL-C: Testing Hypothesis
That “Lower Is Better”
2
Median Change In PAV
CAMELOT
Placebo
1
REVERSAL
Pravastatin
STRADIVARIUS
Placebo
REVERSAL
Atorvastatin
0
ILLUSTRATE
ASTEROID
Placebo
Rosuvastatin
SATURN
–1
Atorvastatin
SATURN
Rosuvastatin
–2
40
60
PAV = percent atheroma volume
Puri R, et al. European Heart J 2013;13:1818-1825.
80
100
Average On-Treatment LDL-C (mg/dL)
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
17
120
Coronary Intravascular Ultrasound (IVUS)
Study Schema
Population
Clinical indication for coronary angiography
Fasting LDL-C ≥ 60 mg/dL
RANDOMIZATION
•
•
Primary Endpoint
Placebo QM
(N = 475)
•
Change in PAV from
baseline
Secondary Endpoints
•
Evolocumab QM
(N = 475)
•
•
IVUS Measurements
Week 78
Screening
Data expected 2016
TAV = total atheroma volume
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
18
Change in TAV from
baseline
Regression in PAV
Regression in TAV
Our Outcomes Study Is Also Exploring Levels
of LDL-C Not Previously Achievable
Population
•
•
Clinically evident cardiovascular disease at high risk for a recurrent event
Median baseline LDL-C expected to be in the range of 90–100 mg/dL
Background Therapy
Effective statin therapy +/- ezetimibe
RANDOMIZATION
•
Evolocumab
(N = 13,750)
Evolocumab 140 mg Q2W or 420 mg QM
Placebo
(N = 13,750)
Composite Primary
Endpoint
Time to:
• CV death
• Myocardial infarction
• Stroke
• Hospitalization for
unstable angina
• Coronary
revascularization
Increasing enrollment by 5,000 patients
Outcomes data expected no later than 2017 (event driven)
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
19
Summary
•
Evolocumab has been developed with Q2W and QM dosing regimens that
are clinically equivalent
•
Safety and efficacy in patients that achieved very low LDL-C were comparable to
those that achieved higher LDL-C
– Neurocognitive AE rates did not differ according to treatment assignment
or achieved LDL-C
– Adjudicated cardiovascular events trended favorably in the evolocumab-treated cohort
•
Evolocumab reduced LDL-C and frequency of apheresis in some patients
with HoFH and severe FH
•
IVUS study underway to demonstrate reduction in plaque burden
•
Well powered study underway to demonstrate improvement in CV outcomes
Testing the hypothesis for LDL-C that “Lower Is Better”
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
20
AHA Scientific Sessions 2014
Conference Call
Q&A
Provided November 18, 2014, as part of an oral presentation and is qualified
by such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
21