Introducing Carfilzomib &
Clinical Trial Participation
Brian GM Durie, MD
Cedars-Sinai, Los Angeles
September 8, 2011
Today's Discussion
· About carfilzomib
Background
Clinical development update
· Clinical trials and why they're important
· ASPIRE Phase 3 clinical trial
· Your questions
How Carfilzomib Got Its Name
Phil Whitcome
1949-2005
· Scientist
· Businessman
· Entrepreneur
· Philanthropist
Wife: Carla Whitcome
Car fil zomib
3
Targeting the Proteasome in Myeloma
· The proteasome acts as the cell's
recycling center and breaks down
proteins that may be dysfunctional or
no longer needed
· Proteasome inhibition causes cancer
cells (particularly myeloma) to die
· Velcade (bortezomib) was the first
proteasome inhibitor tested in clinical
trials
· Bortezomib's effectiveness against
myeloma shows that the proteasome
is a proven target
Crystal structure of epoxyketone proteasome
inhibitors binding the proteasome
4
Mol. Cancer. Therapeutics, 2005;4:686
How is Carfilzomib Administered?
· Administered IV over 2-10 minutes
· 28-day cycle with dosing on days 1, 2, 8, 9, 15, 16
Day 1 Day 2
Day8 Day 9
Day 15 Day 16
0
28-day
cycle
Rest
period (12
days)
proteasome
inhibition 80
%
Week 12
3
4
5
Carfilzomib: Planned Development
Pathways
First Potential Indication
Relapsed/refractory after treatment with Velcade and an IMiD
Potential Treatment Expansion
Relapsed setting - in combination with Revlimid/dex
Future Development Opportunities
1st-line myeloma, lymphoma and solid tumors
6
Carfilzomib Phase 2b Results in Relapsed and
Refractory Multiple Myeloma
Evaluable Population
257 Patients
Average of 5
Prior Therapies
regimens
Overall Response Rate
24%
Duration of Response
7.8 months
Overall Survival
15.6 months
Grade 3/4 Neuropathy
Less than 1%
7
Source: ASCO 2011, D. Siegel, et al.
Newly Diagnosed Study:
Promising Early Data
Phase 1/2 Study of Carfilzomib + Lenalidomide + Dexamethasone
in patients with newly diagnosed multiple myeloma
2 cycles
4 cycles
8 cycles
Response, %
(n=33)
(n=29)
(n=18)
sCR/CR/nCR
27
41
61
VGPR
42
62
83
PR
97
97
100
8
Source: IMW 2011, A. Jakubowiak, et al.
Summary of Carfilzomib in
Multiple Myeloma
· An active agent studied in myeloma
Overall response rate (ORR); duration of response
(DoR); overall survival (OS)
· Robust activity as a single-agent and in
combination
· Promising front-line efficacy
· Safety profile appears to support extended
treatment and easy combinability
9
When Could Carfilzomib Be Available to
Patients?
· "Fast Track" designation granted
· Allows Onyx to submit sections of the New Drug Application (NDA)
as they are completed
· Pre-clinical module submitted
· Submitting NDA filing through an accelerated approval
registration pathway
· Requesting Priority Review of the application
· Shortens FDA review time from one year to six months
· Pending FDA review and potential approval, carfilzomib could
be available to patients during the first half of 2012
· Relapsed and refractory multiple myeloma
10
Reasons Patients May Choose to
Participate in a Clinical Trial
· Play a more active role in their own health care
· Gain access to emerging treatments before they are
widely available
· Help others by contributing to medical research
· Trust their physician's recommendation
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ASPIRE Phase 3 Study
· ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus
Lenalidomide and Dexamethasone for the treatment of PatIents with
Relapsed Multiple MyEloma)
· Large, Phase 3 international, multi-center clinical study enrolling 700
patients
· Exploring whether the treatment triplet can extend the time a patient
lives without their disease worsening, also known as progression-free
survival or PFS
· Trial initiated based on positive results from a Phase 1b/b study
evaluating the treatment triplet
78% overall response rate1
12 1. Interim Phase 2 results presented at ASCO 2011.
ASPIRE Trial Design
Cycles 1 and higher
(28 days each)
700 patients,
Dexamethasone
Lenalidomide/Dexamethasone Arm
1:1
Days 1, 8, 15, 22
Randomization
Lenalidomide
Days 121
Cycles 112
Cycles 1318
Cycles 19 and higher
(28 days each)
(28 days each)
(28 days each)
Carfilzomib
Carfilzomib
Dexamethasone
Days 1, 2, 8, 9, 15, 16
Days 1, 2, 15, 16
Days 1, 8, 15, 22
CRd Arm
Dexamethasone
Dexamethasone
Lenalidomide
Days 1, 8, 15, 22
Days 1, 8, 15, 22
Days 121
Lenalidomide
Lenalidomide
Days 121
Days 121
13
Eligibility Criteria
· Participants in the study must:
Be at least 18 years old
Have symptomatic multiple myeloma
Have relapsed disease after 1-3 prior treatment regimens:
May have been previously with:
· Bortezomib (Velcade)
· IMiD: Thalidomide (Thalomid) or lenalidomide (Revlimid)
· Participants will not be considered eligible for the study if they:
Discontinued previous lenalidomide or dexamethasone treatment due to
intolerance
· Subjects who are intolerant to bortezomib are still eligible
Were previously treated with carfilzomib
· This is a partial list of inclusion/exclusion criteria
14
Clinical Trial Locations*
Alberta
Manitoba
New Jersey
Arizona
Massachusetts
New York
British Columbia
Michigan
Nova Scotia
California
Minnesota
Ontario
Colorado
Mississippi
Pennsylvania
Connecticut
Missouri
Quebec
Florida
Nebraska
Tennessee
Illinois
Nevada
Texas
Indiana
Newfoundland
North Carolina
Kansas
New Brunswick
Washington State
Kentucky
New Hampshire
Wisconsin
15 *Not all sites are actively recruiting patients
Five Ways to Find an ASPIRE Site
Near You
· Visit the Clinical Trials Section of International Myeloma
Foundation's (IMF) website
· Call the IMF Hotline at 800-452-CURE (2873)
· Call the Multiple Myeloma Research Foundation's Patient
Navigator Hotline at 866-603-MMCT (6628)
· Call the Onyx Medical Information Hotline at
877-ONYX-1-2-1 (877-669-9121) or email
medinfo@onyx-pharm.com
· Visit ClinicalTrials.gov and search for NCT01080391
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Questions