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Differentiate the Brand
The market is very competitive...
Licensed
Indications
Women at
increased
risk*
Data &
Ongoing
Studies
Noninvasive
cancer
(DCIS)
Early BC –
Primary
Adjuvant
Early BC –
Extended
Adjuvant
1st Line
advanced
BC
2nd Line
advanced
BC
Differentiation
• Clinical differentiation vs tamoxifen
• Clinical differentiation from AI’s
• Data differentiation from AI’s
• Marketing/sales differentiation
The major focus today will be
differentiation from AIs focusing on
ARIMIDEX vs letrozole.
Treatment options in early breast cancer
Anastrozole Letrozole Exemestane
Initial adjuvant
therapy
Efficacy vs tamoxifen
Tolerability
Full risk:benefit
profile
Switching from
tamoxifen
Efficacy vs tamoxifen
Tolerability




?



Extended
Efficacy vs placebo
adjuvant setting
Tolerability
?

?
Key Issue: Differentiation vs letrozole
Establish Arimidex as the standard of care for early BC
Comparison of safety between
ATAC and BIG 1-98
Compared with tamoxifen
Hot flushes
Vaginal bleeding
Vaginal discharge
Hysterectomy
Endometrial cancer
Cardiovascular events (grade 3-5)
Cardiovascular deaths
Cerebrovascular deaths
Thromboembolic events
Joint symptoms
Fractures
Anastrozole





NS





Letrozole


?
?
NS




?

There are clear differences in the safety profiles of anastrozole and
letrozole in the primary adjuvant setting
?=not reported, NS=non-significant
Letrozole Strategy
• Treatment effectiveness vs duration
– No duration of treatment data for AIs beyond 5 years
– Clinical decision therefore a balance between
• AI from start for 5 years OR
• TMX first then extending adjuvant for a further 5 years
• Deal with this  Stratify patients
– High risk – Start with most potent option –letrozole for 5 years
– Low risk – Start with tamoxifen for 5 years, then letrozole for 5
years
Letrozole Sales Story Flow
Letrozole is more potent and superior to Arimidex and TMX
In high risk patients
GIVE 5 YEARS PRIMARY ADJUVANT THERAPY WITH LETROZOLE
Lower risk – trade lower initial efficacy for long term duration
as low risk patients are less likely to relapse early
GIVE 5 YEARS TMX FOLLOWED BY 5 YEARS LETROZOLE
Letrozole is the only treatment shown to significantly reduce risk of recurrence both
as initial therapy post-surgery and also following standard tamoxifen
Letrozole has the broadest and most impressive efficacy dataset across the
breast cancer continuum
Guiding Principles for Marketing &
Sales Teams
1. Don’t be distracted
2. Focus on replacing tamoxifen
3. Stay focused on the Arimidex core story flow
4. Be confident – Arimidex is the best endocrine
treatment option
Core Story Flow (1)
The BC diagnosis is a period of great uncertainty for a woman
She wants to be reassured that she has the best possible chance that the
BC will not come back
Tamoxifen is now no longer the best you can offer
It is no longer optimal adjuvant therapy
With ‘Arimidex’ you can be confident you are doing the best that you can
to reduce the risk of her BC coming back or of her dying of the disease
You can reassure her that you are giving her the best that you have to offer
We know from the Oxford Overview that the risk of recurrence is
greatest in the first 5 years post diagnosis – irrespective of nodal
status, receptor status or tumour size
So it is important to use the most effective treatment from the outset
Core Story Flow (2)
She will have a lower risk of breast cancer recurrence, a lower risk of
contralateral breast cancer and a lower risk of life threatening
distant recurrence whether she starts or switches to ‘Arimidex’
The other thing women worry about when making treatment decisions is
‘how will this treatment affect me? What are the side effects?
Arimidex has a significantly better safety profile than tamoxifen with
a lower risk of serious adverse events such as thrombosis, stroke and
endometrial cancer
There are marked differences in the safety of AIs when used in the
adjuvant setting and the AIs can not be used interchangeably.
Core Story Flow (3)
The full benefit/risk profile of ‘Arimidex’ is known
Only ‘Arimidex’ has established efficacy and safety with more than 5 years
long term follow up data
You can give her more certainty at an uncertain time.
‘Arimidex’ provides her the best possible chance to beat breast cancer and more
assurance about the safety of her treatment.
Isn’t this the best you can offer her?
This is why ‘Arimidex’ is now the best
endocrine treatment option and the new
standard of care in early breast cancer
Our Position on BIG 1-98
• The trial provides more evidence that TMX is no longer the standard of
care in postmenopausal women with early breast cancer
• There are no overall efficacy benefits emerging from this early analysis
that have not already been demonstrated by ATAC
• However, at 26 months BIG 1-98 raises serious safety concerns –
stroke, cardiac events, hypercholesterolemia
• Unlike Arimidex , the most selective of the AIs, letrozole does not
appear to reduce the risk of endometrial cancer
• With 68 months follow up in ATAC, the numerous safety and tolerability
benefits of Arimidex vs tamoxifen are known
• There are marked differences in the safety of AIs when used in the
adjuvant setting and BIG 1-98 provides evidence (thank you) that they
cannot be used interchangeably
• Only Arimidex has a full 5-year risk:benefit profile with more than 5 years
long-term follow-up data in the primary adjuvant setting
Based on the evidence above Arimidex remains the best
endocrine treatment option and the best standard of care for
postmenopausal women with hormone-sensitive early breast cancer
Customer Segments - Delivering the message
Tamoxifen die-hard
Mixture of tam /
Arimidex/AI
Arimidex/AI is my
standard in EBC
Letrozole User
CORE STORY FLOW
Drive ATAC
CORE STORY FLOW
CORE STORY FLOW
CORE STORY FLOW
-Challenge TAM
standard of care.
-Highlight lack of
overall efficacy benefit
-Differentiate from AI
based on data
maturity and safety
-Differentiate from AI
based on:
-Safety
-Data maturity
Letrozole User
•Proactive letrozole messaging
All others
•Reactive letrozole messaging
-Only AI licenced
Why take the risk with
letrozole?
-Highlight lack of
overall efficacy
benefit
-Differentiate from AI
based on:
-Safety
-Data maturity
-Only AI
licenced
Why take the risk
with letrozole?
Key AI Data
expected in 2005/2006
• BIG 1-98 St Gallen 2005
• Arimidex extended adjuvant (ABCSG6) ASCO 2005
• Exemestane adjuvant (TEAM) Q1 2006
• Letrozole switch data (BIG 1-98) Q4 2006
Only Arimidex
Arimidex
The most selective AI
No clinically relevant
effect on adrenal function
No clinically relevant
effect on lipid profiles
No clinically significant
drug interactions
Letrozole
Exemestane
X
X
X
X
X
No androgenic,
oestrogenic or
progestogenic activity
Acceptable cardiac /
stroke profile
No impact on subsequent
lines of hormonal therapy
No data
X
X
X
lipids
No data
No data
Differentiation – Adrenal Function
Selective inhibition of aromatase is essential to avoid toxicity
due to disturbance of complex pathways of steroid synthesis
• Arimidex -no significant effect on basal or ACTH-stimulated
adrenal function
– In post menopausal women over 3 months at 10x the standard
clinical dose over 3 months in ABC
• Letrozole – significant impact on adrenal function
– in postmenopausal women with ABC at standard dose for 3 months
– is less selective than Arimidex
• Exemestane – no significant effect on basal concentrations
– no data on ACTH-stimulated cortisol and aldosterone
The long-term clinical differences between Arimidex and
letrozole are still to be determined but has the poetntial to
become clinically relevant in the long-term 5 year adjuvant
treatment of early breast cancer.
Differentiation – Lipids
Change in lipid profiles are major risk factors for CHD, MI and
stroke
• Arimidex -no clinically relevant effect on lipid profiles
– In 3 month and long-term studies Arimidex has shown no clinically
relevant impact on lipid profiles
• Letrozole – significant adverse effects on serum lipid
profiles in postmenopausal women with ABC
– significantly affected lipid profiles and increased atherogenic risk
ratios
• Exemestane – appears to have unfavourable effect on
serum lipid profiles in postmenopausal women with ABC
– including reducing HDL cholesterol and increasing LDL
Data from the advanced setting suggest that letrozole and
exemestane may have the potential to produce adverse effects
on lipid profiles when administered long term.
Differentiation – Androgenic,
oestrogenic and progestogenic activity
Side effects of androgenic activity distressing and potentially
dangerous
• Arimidex –no androgenic, oestrogenic or progestogenic
activity observed in 1,000,000 patient years experience
– Is that enough ?!
• Letrozole – no androgenic, oestrogenic or progestogenic
activity observed
• Exemestane – androgenic side effects reported at clinical
doses in patients with ABC
– including acne, hirsutism and weight gain
– due to the fact that it is a steroidal molecule, designed to mimic
androgens and to bind into the androgen-binding site on the
aromatase enzyme
Arimidex and letrozole exhibit no adverse androngenic,
oestrogenic or progestogenic activity
Differentiation - Bone
Arimidex : Impact on bone is known and manageable
• ATAC trial data quantify the long term effects of Arimidex
on bone in women with early breast cancer
– The overall risk:benefit ratio is in favour of Arimidex over TMX
• Letrozole – claiming that fracture risk is lower on BIG 198 than ATAC
– but fracture rate per 100 patient years = 2.2 in each trial
– no information re co-prescription of biphosophonates
– mean age of ATAC patients 3 years older and 25% US patients
• Exemestane – no evidence of any positive impact on
bone mass in women with breast cancer
– no published data on fractures
– exemestane claims are on rats and healthy volunteers
– no robust BMD data from a relevant patient population
Arimidex is the only AI with long-term data quantifying its impact
on bone in women with early breast cancer.
Differentiation – CV Class Effect
Is CV toxicity a class effect ? Novartis say it is …..
• Arimidex – CV events do not represent a serious safety issue
– No statistical difference between Arimidex and tamoxifen
– no significant effect on lipid profile, and +ve effect on HDL
• Letrozole – CV events DO represent a serious safety issue
–
–
–
–
marked difference in favour of tamoxifen – MI and stroke
letrozole is less selective then Arimidex
non-selective AIs are known to cause side effects (Cytadren)
appears to have an unfavourable effect on lipid profile
Differences between AIs result in differences in safety profiles
when given long-term. This seems to be evident when
considering the effect of the AIs on cardiovascular events.
Summary
• A fully established risk:benefit profile has not
been established for letrozole
Only Arimidex has a fully established long-term
risk-benefit profile with data covering the full
recommended 5-year treatment period
Marketing Tools
Differentiation Support Materials
• Arimidex vs letrozole issues management
document
• ATAC vs BIG1-98 slides set including key slides
to support the selectivity argument
• To follow objection handlers
– CV events
– Sequencing vs switch
– Sub groups
Other Activities…..
• Publications
–
–
–
–
CV deaths – Lancet letter to editor
Full risk/benefit – manuscript in development
Differentiation – review articles
Consensus Groups
• Meetings/Symposia Differentiation messages based
on the BIG 1-98 result are being incorporated into all
planned meetings/symposia
• Differentiation Core brand package Materials to be
updated
• Global Differentiation Market Research Project
Arimidex IPEP
In Practice Evaluation Program
What is an IPEP?
A marketing driven data collection
programme in a real world situation
based around physicians prescribing a
licensed drug to demonstrate product
benefits and to gain physician buy-in
Summary
• A tool for promoting change in prescribing practice
(switch from tamoxifen to Arimidex), based on positive
‘hands-on’ experience
• Scientific basis generates buy-in from clinicians
• Creates relationships / marketing opportunities
BUT
• Must be in accordance with local guidelines
• Requires forethought and planning for maximum
success
Not a clinical trial !!!
• No rigid inclusion/exclusion criteria
• Comorbidity and polypharmacy not excluded
• In real life within approved product label
• On prescribed drugs or samples
• Post local approval
• No intensive monitoring of patients: “as usual”
• Driven by Marketing & Sales Departments
P res crip tio n s b y p ro d u c t
R x /Q T R F 2 0 (S c h izo p h ren ia )
P re s c rip tio n s b y p ro d u c t
R x /Q T R LEPONEX
F 2 0 ( S c hZELDOX
izo p h reAMITREX
n ia )
SEROQUEL
8,000
SEROQUEL
LEPONEX
ZELDOX
AMITREX
ALZEN
ALZEN
8.000
7,000
IPEP launch
7.000
IPEP launch
6.000
518% growth
6,000
518% growth
5.000
4.000
5,000
3.000
2.000
4,000
1.000
0
3,000
RX
OCT-DEC/02
RX
JAN-MAR/03
RX
APR-JUN/03
RX
JUL-SEP/03
RX
OCT-DEC/03
RX
JAN-MAR/04
RX
APR-JUN/04
RX
JUL-SEP/04
2,000
1,000
0
RX
OCT-DEC/02
RX
JAN-MAR/03
RX
APR-JUN/03
RX
JUL-SEP/03
RX
OCT-DEC/03
RX
JAN-MAR/04
RX
APR-JUN/04
RX
JUL-SEP/04
Role of Sales & marketing
• Drive recruitment of right doctors to maximise returns
• Pull through activities
• Investigator meetings during and after the IPEP
• Collect data sheets
• Creation of advocates
• Speakers
• Publications/case reports etc
• Deliver full results summary
Role of representatives
• Active promotion by the representative is vital for
the success of the IPEP
• Ongoing nature of the programme creates
opportunities over many months
• Aim to work with physicians as partners in a
scientific investigation, as opposed to a
traditional selling role
• Appropriate training for the sales force is
therefore essential
Logistics of Arimidex IPEP program
• Clinician to recruit 5 patients who are currently
receiving tamoxifen and are suitable for switch to
Arimidex!
• Baseline assessment and questionnaire
• Follow up after 3 months (or whatever is local
practice)
• Final assessment after a further 3 months
• Analysis of data
Components of the Arimidex IPEP folder
• Branded rationale - Mini detail aid highlighting benefits
of Arimidex in ATAC and ABCSG/ ARNO studies
• Invitation letter for doctor and patient
• Instructions for doctor
• Patient information leaflet
• CRF
• Patient questionnaire
• CD ROM containing graphics, files and implementation
guide
Outline of ARREST – Dutch Experience
Arimidex: Reason & Effect of Switch from Tamoxifen
• 200 patients in 70 centres
• Questionnaire
– 1: patient, reason switch, Fact B; 2: effect, Fact B
• Rep involvement
– Centre selection, briefing & monthly monitoring
• Investment/ROI
– Materials (€ 6000,-), fee (200* € 57,-), time
– More sales & contacts in problematic centres
– More switches on (50/200) and off (??) trial
KOL Activities for Arimidex
KOL Development Opportunities in 2005
•
•
•
•
•
•
•
•
•
Summit Meeting – March 11 - 13
‘Meeting in a Box’ (5% challenge)
Emerging & LCM Ad boards
Focus Groups & KOL Dinners (already planned for Italy &
Japan)
‘Meet the Professor’ Meetings (5% challenge)
Expert Prescribers Forum (Arimidex in premenopausal patients)
Clinicians Working Group (Arimidex in premenopausal patients)
Praeceptorships (visits to key centres by individual or small
groups of doctors)
Global/Regional Innovators programmes
Expert Prescribers Forum
OBJECTIVES
•
To create a new core of Arimidex Global and National Media Spokespeople to
support and defend Arimidex in 2005 and beyond including the concept of use
in premenopausal women
FORMAT/TIMING
•
Speaker presentations in the style of a press briefing to demonstrate the best
way of presenting information to the media
•
Target doctors:
•
–
–
Already acted as a national media spokesperson but need more motivation
Familiar with Arimidex in 1 setting but needs more information about use across the entire BC
continuum
–
Widely respected within the HCP community and could be an influential media spokesperson for
Arimidex if armed with the right information
Meeting to take place at ASCO (May 2005)
OUTPUTS
•
Facilitate National KOL support at local meetings and media briefings
•
Updated speaker slides for use with the Media
•
Increased pool of Global & National KOL Media Spokespeople
•
MC media briefing support pack
COSTS
•
No cost to MC assuming the delegates are already attending ASCO
Meeting in a Box
OBJECTIVES
•
To develop ‘off the shelf’ meeting programmes and content for use as
the basis of local meetings
FORMAT
•
•
•
AZ nominate a Steering Committee to develop the meeting content
Faculty meet over 1 day to agree programme and slide content (3
modules) for local ‘stand-alone’ meetings
Slide set & logistics/organisational package prepared for MCs
OUTPUTS
•
Steering Committee continue to be involved in the initiative through:
– Train the trainers
– Chair or participate in local or regional meetings if required
•
MC & Local KOL refine local meeting content adding:
– Local ‘hot topic’ or area of particular interest to KOL (not necessarily brandrelated)
Costs
•
•
Global will cover all costs associated with preparing the ‘Meeting in a
Box’ resources
MC to budget for local roll out of meetings modules including faculty
travel & honoraria where needed
Meeting in a Box - Timelines/ Milestones
April
• Chair approached & engaged
• SC approached & engaged
May
• SC meeting
June
• Slides prepared
• Logistics pack prepared
July / Aug
• Meetings in a Box 2005 finalised
Aug / November
• ‘Train the trainer’ meetings where needed (country specific)
•
•
Local Meetings held
Decision reached in consultation with MCs over modules for 2006
Developing KOL Advocacy
for the BC Portfolio
Influencing and Advocacy
Mapping
Key opinion Leader Advocacy
• KOL have differing levels of influence in the breast
cancer community and differ in the level to which they
will advocate for our brands
• Brand advocacy is to a large extent within our control
while the level of influence is dependent on external
factors
• Our goal is to ensure those who influence the breast
cancer community are also advocates for our brands
• Leading researchers and academics with knowledge
and expertise in the treatment of specific medical
conditions
– Highly respected by their peers nationally & internationally
– Found in leading medical schools and universities
How can we increase brand advocacy?
• Experience with drug
• Have good results when the drug is used (i.e.
encourage use in the right patients)
• Hear the experience of others who have used
the drug
• Invite opinion on how the drug should be used
Advocacy and Influence can be linked
• Building brand advocacy can in turn build
influence:
– Publications
– International Speaker engagements
– Clinical Trials
– Advisory Board involvement
Influence/Advocacy Grid
5 (high)
I
N
F
L
U
E
N
C
E
4
3
2
1(low)
1(low)
2
3
ADVOCACY
4
5 (high)
Influence/Advocacy Grid
Global
Thought
Leader
Competitor
Advocate
Global
Thought
Leader
4
Global
Competitor
Advocate
Global
Thought
Leader
Global
Thought
Leader
Global
Thought
Leader
Global AZ
Brand
Advocate
3
Global
Competitor
Advocate
Global
Thought
Leader
Global
Thought
Leader
Global
Thought
Leader
Global AZ
Brand
Advocate
2
National
Competitor
Advocate
National
Thought
Leader
National
Thought
Leader
National
Thought
Leader
National
AZ Brand
Advocate
National
Competitor
Advocate
National
Thought
Leader
National
Thought
Leader
National
Thought
Leader
National AZ
Brand
Advocate
5 (high)
I
N
F
L
U
E
N
C
E
1(low)
1(low)
Global
Thought
Leader
Global
Thought
Leader
Global
Thought
Leader
AZ Brand
Advocate
2
3
ADVOCACY
4
5 (high)
Influence/Advocacy Grid – Direction for Development
I
N
F
L
U
E
N
C
E
5
(high)
4
3
2
?
?
1(low)
?
?
1(low)
2
3
ADVOCACY
Key
VIP
Movers/Shapers
‘Rising Stars’
4
5 (high)
Influence/Advocacy Grid – Arimidex – Global Perspective
5 (high)
Eric Winer
Martine Piccart
Paul Goss
Nancy Davidson
G Hortobagyi
Cliff Hudis
4
I
n
f
l
u
e
n
c
e
3
Kathy
Pritchard
Trevor Powles
Matt Ellis (a)
Aman Buzdar
Jonas Bergh
Jim Ingle
Jack Cuzick
Aron
Goldhirsch
Dan Hayes
B Thurlimann
Mike Baum
Rich Gelber
Harold Burstein (a)
John Forbes
R Margolese
J Klijn
M Castiglione
Lori Goldstein
Melody Cobleigh
W Jonat
R Chlebowski
Kathy Albain
T Maumounas
Tony Howell
J-M Nabholtz (a)
Monica Morrow
A Costa
W Eiermann
R Carlson
R Jakesz (a)
M Dowsett
2
H Mouridson
Jacek Jassem
Antonio Wolff (a)
L Fallowfield
Gershon Locker
Kurt Possinger
Louis Mauriac
M Kaufmann
J Robertson
Jeff Tobias
M Martin
M Constenla
B McCormick
R Bianco
W Gradishar
J Mackey
R Mansell
P Ravdin
L Fallowfield
1(low)
Moise Namer
Advocacy
R Sainsbury
Richard Bell Sean
Duffy
W Distler
R Coleman
Patient Outreach
• Mobilise use of patient support groups
– eg interactive guide to AI CD
– use to disseminate data in easy to understand format
– awareness of options available to patients
• Early Detection
– self examination
• Breast Cancer Month
– How to raise awareness of disease, treatment options
• Use national media, magazines
– Sell in stories from ASCO
PR Opportunities
• Maximise extended adjuvant data - ASCO
• ‘ATAC publication
• St Gallen guidelines
• Local initiatives
• Case studies
Syndicate
• What do we need to do in order to increase our
marketing differentiation for Arimidex ?
• Please consider national, regional, global requirements
• Can include subjects we have already discussed ….
or brand new ideas
• Try to think of long-term, integrated strategic
requirements, in addition to short-term needs
• Could include IPEPs, promo materials, regional/national
events, KOL advocacy, nominations to Expert
Prescriber Forum, trials, training, PR, information …..
• Please present your ‘Wish List’ back to the group