Differentiate the Brand
The market is very competitive...
Women atincreased risk*Noninvasivecancer(DCIS)1stLineadvancedBC2ndLineadvancedBCEarly BC Primary AdjuvantEarly BC Extended AdjuvantLicensed IndicationsData & Ongoing Studies
DifferentiationClinical differentiation vs tamoxifenClinical differentiation from AIsData differentiation from AIsMarketing/sales differentiation The major focus today will be differentiation from AIs focusing on ARIMIDEX vs letrozole.
Treatment options in early breast cancer AnastrozoleLetrozoleExemestaneInitial adjuvant therapy
Efficacy vs tamoxifenTolerabilitySwitching from tamoxifenEfficacy vs tamoxifenTolerabilityExtended adjuvant settingEfficacy vs placeboTolerability? ? ? Full risk:benefit profileKey Issue: Differentiation vs letrozole Establish Arimidex as the standard of care for early BC
Comparison of safety between ATAC and BIG 1-98There are clear differences in the safety profiles of anastrozole and letrozole in the primary adjuvant settingLetrozole??NS ?Anastrozole NSHot flushesVaginal bleedingVaginal dischargeHysterectomyEndometrial cancerCardiovascular events (grade 3-5)Cardiovascular deathsCerebrovascular deathsThromboembolic eventsJoint symptomsFracturesCompared with tamoxifen?=not reported, NS=non-significant
Letrozole StrategyTreatment effectiveness vs durationNo duration of treatment data for AIs beyond 5 yearsClinical decision therefore a balance between AI from start for 5 years OR TMX first then extending adjuvant for a further 5 yearsDeal with this Stratify patientsHigh risk Start with most potent option letrozole for 5 yearsLow risk Start with tamoxifen for 5 years, then letrozole for 5 years
Letrozole Sales Story Flow
Guiding Principles for Marketing & Sales TeamsDont be distractedFocus on replacing tamoxifenStay focused on the Arimidex core story flowBe 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 backTamoxifen 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 sizeSo 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 dataYou 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. Isnt this the best you can offer her?This is why Arimidex is now the bestendocrine treatment option and the new standard of care in early breast cancer
Our Position on BIG 1-98The trial provides more evidence that TMX is no longer the standard of care in postmenopausal women with early breast cancerThere are no overall efficacy benefits emerging from this early analysis that have not already been demonstrated by ATACHowever, at 26 months BIG 1-98 raises serious safety concerns stroke, cardiac events, hypercholesterolemiaUnlike Arimidex , the most selective of the AIs, letrozole does not appear to reduce the risk of endometrial cancerWith 68 months follow up in ATAC, the numerous safety and tolerability benefits of Arimidex vs tamoxifen are knownThere 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 interchangeablyOnly 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 forpostmenopausal women with hormone-sensitive early breast cancer
Customer Segments - Delivering the message CORE STORY FLOWHighlight lack of overall efficacy benefitDifferentiate from AI based on:SafetyData maturity Only AI licenced Why take the risk with letrozole? Letrozole User Proactive letrozole messagingAll othersReactive letrozole messaging
Key AI Data expected in 2005/2006BIG 1-98St Gallen 2005Arimidex extended adjuvant (ABCSG6) ASCO 2005Exemestane adjuvant (TEAM) Q1 2006Letrozole switch data (BIG 1-98) Q4 2006
Differentiation Adrenal FunctionArimidex -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 ABCLetrozole significant impact on adrenal function in postmenopausal women with ABC at standard dose for 3 monthsis less selective than ArimidexExemestane no significant effect on basal concentrationsno data on ACTH-stimulated cortisol and aldosteroneSelective inhibition of aromatase is essential to avoid toxicity due to disturbance of complex pathways of steroid synthesisThe 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 LipidsArimidex -no clinically relevant effect on lipid profiles In 3 month and long-term studies Arimidex has shown no clinically relevant impact on lipid profilesLetrozole significant adverse effects on serum lipid profiles in postmenopausal women with ABC significantly affected lipid profiles and increased atherogenic risk ratiosExemestane appears to have unfavourable effect on serum lipid profiles in postmenopausal women with ABCincluding reducing HDL cholesterol and increasing LDLChange in lipid profiles are major risk factors for CHD, MI and strokeData 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 activityArimidex no androgenic, oestrogenic or progestogenic activity observed in 1,000,000 patient years experienceIs that enough ?!Letrozole no androgenic, oestrogenic or progestogenic activity observed Exemestane androgenic side effects reported at clinical doses in patients with ABCincluding acne, hirsutism and weight gaindue to the fact that it is a steroidal molecule, designed to mimic androgens and to bind into the androgen-binding site on the aromatase enzymeSide effects of androgenic activity distressing and potentially dangerousArimidex and letrozole exhibit no adverse androngenic, oestrogenic or progestogenic activity
Differentiation - BoneATAC trial data quantify the long term effects of Arimidex on bone in women with early breast cancerThe overall risk:benefit ratio is in favour of Arimidex over TMX Letrozole claiming that fracture risk is lower on BIG 1-98 than ATACbut fracture rate per 100 patient years = 2.2 in each trialno information re co-prescription of biphosophonatesmean age of ATAC patients 3 years older and 25% US patientsExemestane no evidence of any positive impact on bone mass in women with breast cancerno published data on fracturesexemestane claims are on rats and healthy volunteersno robust BMD data from a relevant patient populationArimidex : Impact on bone is known and manageableArimidex is the only AI with long-term data quantifying its impact on bone in women with early breast cancer.
Differentiation CV Class EffectArimidex CV events do not represent a serious safety issueNo statistical difference between Arimidex and tamoxifen no significant effect on lipid profile, and +ve effect on HDLLetrozole CV events DO represent a serious safety issuemarked difference in favour of tamoxifen MI and strokeletrozole is less selective then Arimidexnon-selective AIs are known to cause side effects (Cytadren)appears to have an unfavourable effect on lipid profile
Is CV toxicity a class effect ? Novartis say it is ..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
Differentiation Support Materials Arimidex vs letrozole issues management document ATAC vs BIG1-98 slides set including key slides to support the selectivity argumentTo follow objection handlers CV events Sequencing vs switchSub groups