Project Objectives

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Project Objectives
Primary Objective To understand current
practices regarding the use of HIV therapies in
the EU and to assess the market potential of
Atripla.

• Determine current practice patterns in HIV.
• Quantify usage and market potential of agents in
  HIV patients.
• Gain understanding of recent data announced from
  the DAD and ACTG studies.
• Assess the impact of Atriplas label on its
  initial launch.

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Recruitment Study Methodology
QUANTITATIVE RESEARCH

• Quotas and Recruitment Criteria for Survey
• 50 physicians (infectious disease, HIV
  specialists) in the EU
• 2 to 30 years of experience post-residency
• Minimum 40 professional time spent in clinical
  practice
• Currently treat at least 50 (Germany and United
  Kingdom) HIV patients

• Survey Detail
• Self-administered survey
• Approximately 30 minutes duration
• 50 total respondents
• Fielded online from April 21, 2008 to April 30,
  2008

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Respondent Background Information

• Average Years in Practice Post-training 14.0
  Years Range 4 to 30
• Average Percentage of Professional Time
• Dedicated to Patient Care 84.2 Range 50 to
  100

Category of Physicians (n50)
Country
United Kingdom 52 (n26)
Germany 48 (n24)
Specialty
HIV 50 (n25)
Infectious Disease 44 (n22)
Internal Medicine Specialist 6 (n3)
Practice Setting
Academic/Teaching Institution 78 (n39)
Office-based Practice or Clinic 12 (n6)
Community Hospital 4 (n2)
Other 6 (n3)
Practice Location
Urban 94 (n47)
Rural 4 (n2)
Suburban 2 (n1)
Questions S1, S2, S5, S6
5
Respondent Background Information
HIV Patients Managed Mean Range
Currently 213.7 50 - 800
12 Months Ago 202.8 50 - 850
Questions S7 S8
6
DETAILED FINDINGS
SECTION ONE MARKET GROWTH
7
European or Country-Specific Guidelines
British physicians most frequently follow the
BHIVA guidelines and German physicians most
frequently follow the German-Austrian HIV
guidelines.
Guidelines Followed Number of Responses
British HIV Association (BHIVA) 23
German-Austrian HIV 8
Deutsche AIDS Gesellschaft (DAIG) 5
EACS 4
None 4
International 2
American 1
CDC 1
FDA 1
Penta 1
HIVNet 1
Q1. What if any European or country-specific
guidelines do you follow?
n50
Outliers of 400 NHL and 600 CLL patients were
removed from the mean calculation
8
Initiation of Therapy at Higher CD4 Counts Most
Important Driver of HIV Patient Increase
Revised treatment guidelines and more patients
seeking therapy also important drivers.
Importance Ranking for Drivers of Increase in Patients Treated for HIV Importance Ranking for Drivers of Increase in Patients Treated for HIV Importance Ranking for Drivers of Increase in Patients Treated for HIV
Drivers Mean Rank (1-9) Ranked 1
Therapy initiated at higher CD4 count 3.46 24
Revised treatment guidelines 3.90 14
More diagnosed patients seeking therapy 4.14 16
Increased convenience with reduced pill burden 4.86 2
Novel therapies provide more treatment options 4.98 16
Immigration 5.04 14
Higher utilization of HIV diagnostics 5.42 4
Increased risk taking behavior 6.30 8
Easier access to prescription medicines 6.90 2
Other Frequently Mentioned Drivers More
testing/diagnosing of HIV (4 mentions), better
tolerated medications (2), more successful
therapies/better prognosis (2)
Q2. Please rank the following factors that have
led to increased patients treated for HIV?
(1highest influence, 9 lowest influence
n50
9
Respondents Anticipate Increase in Patients on
HAART
HIV patient volume on HAART expected to grow by
9.5 from last year to next year.
Percentage HIV Patients on HAART
Q3. Over time, what percentage of you HIV
patients are treated with highly active
antiretroviral treatment (HAART)?
n50
10
CD4 Counts at Initiation of HAART Steadily
Increasing
Physicians expect CD4 count at initiation of
HAART to increase by 7.1 over the next year.
CD4 Count Prompting Initiation of HAART
Q4. In the following time periods, what CD4 count
prompts the initiation of HAART in HIV patients?
n50
11
DETAILED FINDINGS
SECTION TWO TREATMENT NAÏVE HIV PRACTICE TRENDS
12
In Naïve Patients, 2 NRTI 1 NNRTI Most Common
Nearly two-thirds of Naïve HIV patients receive 2
NRTI 1 NNRTI regimen.
Treatment Naïve Regimens
of Treatment Naïve HIV Patients on Regimen
Q5. For the given points in time, please estimate
the percentage of treatment naïve HIV patients in
your practice that receive the following regimen.
n50
13
Atripla Poised for Major Increase
Atripla expected to rise from 9 to 29 in 12
months.
NRTI-Based Regimen Mean Percentage Treatment Naïve HIV Patients on Each Regimen Mean Percentage Treatment Naïve HIV Patients on Each Regimen Mean Percentage Treatment Naïve HIV Patients on Each Regimen Mean Percentage Treatment Naïve HIV Patients on Each Regimen
12 Months Ago Currently 12 Months from Now Peak
Truvada 42 46 36 35
Epzicom 24 21 16 16
Combivir 21 15 13 11
Atripla 0 9 29 31
Other 13 9 6 6
Q6. For the given points in time, please indicate
the percentage of treatment naïve HIV patients in
your practice receiving the following NRTI-based
regimens.
n50
14
HAART in Naïve Patients Rising Toward 2.5 Years
Current naïve patient treatment duration 27
months.
Typical Duration of HAART (in Months) for
Treatment Naïve Patients
Q7. For your treatment naïve HIV patients, please
give the typical duration of HAART?
n50
15
10 of Naïve Patients Discontinue
Mostly due to side effects, but also due to
compliance issues.
Percentage of Treatment Naïve Patients
Discontinuing Therapy in First Year
Reasons for Discontinuing Number of Responses
Side Effects 28
Pill Burden / Compliance 18
Interactions 4
Switching 2
Q8. Please indicate the percentage of your
treatment naïve patients that discontinue their
therapy in the first year and the reasons why
they discontinue?
n50
16
Convenience Greatest Driver of Truvada in Naïve
Patients
Clinical trial data a relatively minor factor.
Importance Ranking for Factors Influencing Preference for Truvada (Treatment Naïve Patients) Importance Ranking for Factors Influencing Preference for Truvada (Treatment Naïve Patients) Importance Ranking for Factors Influencing Preference for Truvada (Treatment Naïve Patients)
Factors Mean Rank (1-9) Ranked 1
Convenience Ability to combine with Sustiva in single pill (e.g., Atripla) 3.16 18
Treatment guidelines 4.08 25
Favorable overall benefit / risk profile 4.24 15
More favorable tolerability profile vs. Combivir or Epzicom based regimens 4.41 10
Strong peer reviewed clinical data overall 5.00 6
More favorable efficacy profile vs. Combivir or Epzicom based regimens 5.06 14
Negative clinical trial data from other agents (e.g., DAD and ACTG 5201 trials) 5.41 6
Longer duration of therapy vs. Combivir or Epzicom based regimens 5.78 6
Favorable reimbursement 7.86 0
Other Factors Mentioned Good personal
experience (9) Toxicity (3) Renal problems (3)
Administration (2) Clarification on DAD (2)
Hepatitis co-infection (2) convenience (2)
Only answered by respondents with treatment naive
patients currently on Truvada
Q9. Please rank the following factors that
influence your preference for using a Truvada
based regimen in treatment naïve HIV patients in
the next 12 months? (1highest influence, 9
lowest influence).
n49
17
Ability to Combine, Experience Driving
Epzicom/Combivir
Efficacy compared to Truvada a relatively minor
issue.
Importance Ranking for Factors Influencing Preference for Epzicom or Combivir (Treatment Naïve Patients) Importance Ranking for Factors Influencing Preference for Epzicom or Combivir (Treatment Naïve Patients) Importance Ranking for Factors Influencing Preference for Epzicom or Combivir (Treatment Naïve Patients)
Factors Mean Rank (1-9) Ranked 1
Good experience combining with other agents 2.83 26
Longer experience with Combivir or Epzicom based regimens 2.96 35
Treatment guidelines 4.59 7
Strong peer reviewed clinical data overall 4.74 2
More favorable toxicity profile vs. Truvada based regimen 5.43 15
Favorable overall benefit / risk profile 5.54 4
Longer duration of therapy vs. Truvada based regimen 5.85 0
More favorable efficacy profile vs. Truvada based regimen 6.35 4
Favorable reimbursement 6.72 7
Other Factors Mentioned Renal pre-condition
(6) Co-morbidities (4) Combivir preferred (4)
Pregnancy data (4) CV risks (3)
Only answered by respondents with treatment naive
patients currently on Epzicom or Combivir
Q10. Please rank the following factors that
influence your preference for using a Epzicom or
Combivir based regimen in treatment naïve HIV
patients in the next 12 months? (1highest
influence, 9 lowest influence).
n46
18
DETAILED FINDINGS
SECTION THREE TREATMENT EXPERIENCED HIV PRACTICE
TRENDS
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Majority of Experienced Patients on 2 NRTI
Regimens
Respondents believe peak value has already been
achieved.
Treatment Experienced NRTI-Regimens
of Treatment Experienced HIV Patients on Regimen
Q11. For the given points in time, please
estimate the percentage of treatment experienced
HIV patients in your practice that are on 2, 1,
or 0 NRTI containing regimens.
n50
20
Treatment Regimen Type for Experience Patients
Appears Stable
Integrase inhibitor use expected to significantly
increase in one year.
Regimen Mean Percentage Treatment Experienced HIV Patients on Each Regimen Mean Percentage Treatment Experienced HIV Patients on Each Regimen Mean Percentage Treatment Experienced HIV Patients on Each Regimen Mean Percentage Treatment Experienced HIV Patients on Each Regimen
12 Months Ago Currently 12 Months from Now Peak
NRTI 77 76 76 76
PI 55 54 51 51
NNRTI 39 41 40 42
Entry Inhibitor 3 3 6 8
Integrase Inhibitor 1 3 10 13
Chemokine Receptor Inhibitor 0 2 6 8
Q12. For the given points in time, please
estimate the percentage of treatment experienced
HIV patients in your practice that are on the
following regimens (Note should sum to more than
100 due to combination use).
n50
21
Atripla Expected to Be the Major Mover in Coming
Year
Atripla allocation expected to nearly triple in
next twelve months.
NRTI-Based Regimen Mean Percentage Treatment Experienced HIV Patients on Each NRTI-Based Regimen Mean Percentage Treatment Experienced HIV Patients on Each NRTI-Based Regimen Mean Percentage Treatment Experienced HIV Patients on Each NRTI-Based Regimen Mean Percentage Treatment Experienced HIV Patients on Each NRTI-Based Regimen
12 Months Ago Currently 12 Months from Now Peak
Truvada 38 39 38 37
Epzicom 23 20 16 16
Combivir 21 18 13 12
Other 9 8 7 6
Viread monotherapy 4 4 4 4
Epivir monotherapy 3 2 2 2
Emtriva monotherapy 2 1 1 1
Atripla 0 7 19 21
Q13. For the given points in time, please
indicate the percentage of treatment experienced
HIV patients in your practice receiving the
following NRTI regimens.
n50
22
Experienced Patient Treatment Duration Continues
to Climb
3 years currently, expected to increase about 5
months in the next year.
Typical Duration of Treatment Regimen (in months)
for Treatment Experienced Patients
Q14. For your treatment experienced HIV patients,
please give the duration for a typical treatment
regimen?
n50
23
Truvada in Experienced Patients Driven By
Risk/Benefit
Ability to combine into Atripla the second most
important factor.
Importance Ranking for Factors Influencing Preference for Truvada (Treatment Experienced Patients) Importance Ranking for Factors Influencing Preference for Truvada (Treatment Experienced Patients) Importance Ranking for Factors Influencing Preference for Truvada (Treatment Experienced Patients)
Factors Mean Rank (1-9) Ranked 1
Favorable overall benefit / risk profile 3.76 18
Ability to combine with efavirenz in single pill (e.g., ATRIPLA) 4.00 28
Strong peer reviewed clinical data overall 4.44 12
More favorable toxicity profile vs. Combivir or Epzicom based regimens 4.58 6
Achieving similar efficacy seen in published data in my practice 4.82 8
More favorable efficacy profile vs. Combivir or Epzicom based regimens 5.04 8
Negative data from other agents (e.g., DAD and ACTG 5201 studies) 5.1 14
Longer duration of therapy vs. Combivir or Epzicom based regimens 5.8 4
Favorable reimbursement 7.46 2
Other Factors Mentioned Resistance profile (4)
Data/Experience (3) Dosing/Administration (3)
Cheaper (1)
Only answered by respondents with treatment
experienced patients currently on Truvada
Q15. Please rank the following factors that
influence your preference for using a Truvada
based regimen in treatment experienced HIV
patients in the next 12 months? (1highest
influence, 9 lowest influence).
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Epzicom/Combivir in Experienced Due to Track
Record
Risk/benefit profile only the 5th most important
driver.
Importance Ranking for Factors Influencing Preference for Epzicom or Combivir (Treatment Experienced Patients) Importance Ranking for Factors Influencing Preference for Epzicom or Combivir (Treatment Experienced Patients) Importance Ranking for Factors Influencing Preference for Epzicom or Combivir (Treatment Experienced Patients)
Factors Mean Rank (1-9) Ranked 1
Experience combining with other agents 3.17 29
Longer experience with Combivir or Epzicom based regimens 3.50 30
Strong peer reviewed clinical data overall 4.35 4
Achieving similar efficacy seen in published data in my practice 4.43 7
Favorable overall benefit / risk profile 4.65 15
Longer duration of therapy vs. Truvada based regimen 6.07 2
More favorable efficacy profile vs. Truvada based regimen 6.09 7
Favorable reimbursement 6.22 4
More favorable toxicity profile vs. Truvada based regimen 6.52 2
Other Factors Mentioned Resistance profile (3)
Pregnancy data (3) Dosing/administration (3)
Use in various patients (2) Other drugs (3)
Cheaper (1)
Only answered by respondents with treatment
experienced patients currently on Epzicom or
Combivir
Q16. Please rank the following factors that
influence your preference for using Combivir or
Epzicom based regimens in treatment experienced
HIV patients in the next 12 months? (1highest
influence, 9 lowest influence).
n46
25
Vast Majority Willing to Use Truvada in Both
Settings
Largely depends on resistance.
Use of Truvada in Both Treatment-Experienced and
Treatment Naïve Settings for the Same Patient
Yes (Comments) Depends on Resistance
(21) Depends on Tolerability/Efficacy
(12) Possible Activity (3)
of Respondents
No (Comments) Lack of Approval (1) Backbone
Change (1) Doesnt Work (1)
Q17. If a HIV patient received a Truvada based
regimen in the treatment naïve setting, would you
consider also using it in the treatment
experienced setting?
n40
26
15 of Experienced Patients Become Resistant to
Tenofovir
Combovir/Epzicom also considered appropriate in
both settings by most.
Combivir/Epzicom Use in Both Experienced and
Naïve HIV Patients
Percentage of Experienced HIV Patients Becoming
Resistant to Tenofovir
Yes (Comments) Depends on Resistances
(23) Depends on Efficacy (9) Depends on Genotype
(3)
No (Comments) Depends on Resistance (3) Doesnt
Work (1) Side Effects (1) Unless Others Ruled Out
(1)
of Respondents
of Treatment
n50
n15
Q18. In your experience, what percent of your
treatment experienced HIV patients become
resistant to tenofovir? Q19. If a HIV patient
received a Combivir or Epzicom based regimen in
the treatment naïve setting, would you consider
also using it in the treatment experienced
setting?
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DETAILED FINDINGS
SECTION FOUR ATRIPLA SPECIFIC QUESTIONS
The EMEA recently approved ATRIPLA, a single pill combination of emtricitabine, tenofovir, and efavirenz, for the treatment of HIV infection in adults with virologic suppression to HIV-1 RNA levels less than 50 copies/ml on current combination antiretroviral therapy for more than three months. Patients must not have experienced biological failure on any prior antiretroviral therapy and must be known not to have harbored virus strains with mutations conferring significant resistance to any of the three components contained in ATRIPLA prior to initiation of their first antiretroviral treatment regimen.
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Respondents Average 13.5 Patients on Atripla
Range 0-60
HIV Patients on Commercial Atripla HIV Patients on Commercial Atripla HIV Patients on Commercial Atripla
Mean Number of Patients Median Range
13.5 10.0 0-60
Q20. How many patients have you put on a
commercial Atripla regimen?
n50
29
TruvadaSustiva Most Common Before Atripla
CombovirSustiva a distant second place.
Top Prescribing Regimens Before Switching to Atripla n Mean Rank Ranked 1
Truvada Sustiva 32 1.1 91
Combivir Sustiva 18 2.4 6
Epzicom Sustiva 16 2.3 13
Truvada Virimmune 9 2.2 0
Truvada any PI 5 2.4 0
Combivir other 5 2.8 0
Combivir any PI 4 1.5 75
Truvada other 4 2.5 0
Combivir Virimmune 3 2.7 0
Other 3 2.7 0
Combivir alone 2 2.0 0
Epzicom any PI 2 2.5 0
Combivir Stocrin 2 3.0 0
Truvada alone 1 2.0 0
Epzicom alone 1 3.0 0
Epzicom Stocrin 1 3.0 0
Epzicom Virimmune 0 0.0 0
Epzicom other 0 0.0 0
Truvada Stocrin 0 0.0 0
Q21. Please indicate the top 3 most common prior
regimens before switching to Atripla.
n50
30
40 of Naïve Patients Deemed Atripla Eligible
Slightly less (34) of treatment experienced
patients deemed eligible for Atripla.
HIV Patients Eligible for Atripla
of Patients
Q22. What percentage of your treatment naïve and
treatment experienced HIV patients are currently
eligible for Atripla based on its labeled
indication (See specific label above)?
n50
31
72 of TruvadaSustiva Patiens Will Switch
42 of Combovir Sustiva will switch.
HIV Patients on Truvada Sustiva or Combivir
Sustiva to Switch to Atripla in the Next 12 Months
of Patients
Q23. Please indicate the percentage of your
Truvada Sustiva and Combivir Sustiva that
will switch to Atripla in the next 12 months.
Please comment on your reasoning for not
switching all patients?
n50
32
More than Half Expect Label Will Limit Naïve Use
Still, 40 suggested that it would not.
Atriplas Label Specification to Limit Use in
Naïve HIV Patients
Yes (Comments) Cant/Wont Go Against Label
(14) May Switch Later (5) Depends on Other
Regimens (3)
No (Comments) Do/Will Use (12) May Switch Later
(4)
of Respondents
Q24. Do you believe that ATRIPLAs labeled use
for the treatment of HIV infection in adults
with virologic suppression to HIV-1 RNA levels
less than 50 copies/ml on current combination
antiretroviral therapy for more than three
months will limit your use of ATRIPLA in
treatment naïve patients?
n50
33
Half Will Follow Label for Experienced Patients
As many stated they were already using in this
group as said they would follow the restriction.
Atriplas Label Specification to Limit Use in
Experienced HIV Patients
Yes (Comments) Approval/Restrictions
(13) Depends on Previous Tx, Resistances (7)
No (Comments) Already Use, No Effect (15) Not
Relevant / Few Eligible (8)
of Respondents
Q25. Do you believe that ATRIPLAs labeled use
for the treatment of HIV infection in adults
with virologic suppression to HIV-1 RNA levels
less than 50 copies/ml on current combination
antiretroviral therapy for more than three
months will limit your use of ATRIPLA in
treatment experienced patients?
n50
34
Atripla Viewed Very Positively Overall
Compliance the obvious primary reason minority
claimed not a major advance.
Overall Opinion of Atripla (select comments) Number of Responses
One Pill / Compliance Win 31
General Positive Comment 20
Not a Substantial Change 4
Side Effects Still an Issue 3
Q26. What is your overall opinion of ATRIPLA and
how it influences your treatment decisions in
HIV?
n50
35
Overall Use of Truvada Expected to Increase in
Naive
Similar use overall in experienced HIV patients.
Anticipated Truvada Use Given Atriplas Approval
Stay the Same
of respondents
Decrease
Increase
Q27. Given the approval of Atripla, do you
expect your use of Truvada either alone or in
combination to increase, decrease, or stay the
same in treatment naïve patients and treatment
experienced patients?
n50
36
DETAILED FINDINGS
SECTION FIVE RECENT CLINICAL DATA
Results from two recent studies, the DAD study and the ACTG 5202 study, were recently reported. Brief summaries of each of these studies are presented below. DAD Study Designed to test whether NRTIs increase the risk of myocardial infarction (MI) in HIV patients. The trial used Poisson regression models to quantify the relation between cumulative, recent (currently or within the preceding 6 months), and past use of zidovudine, didanosine, stavudine, lamivudine, and abacavir and development of myocardial infarction in 33,347 patients. There was no association between the rate of MI and cumulative or recent use of zidovudine, stavudine, or lamivudine. In contrast, recent - but not cumulative - use of abacavir or didanosine was associated with an increased rate of MI (compared with those with no recent use of the drugs, relative rate 190, 95 CI 147245 p00001 with abacavir and 149, 114195 p0003 with didanosine). ACTG 5202 Study Designed as a randomized double-blind comparison of emtricitabine tenofovir vs. abacavir lamivudine. The trial showed virologic failure rates were significantly higher amongst those randomized to abacavir lamivudine than to tenofovir emtricitabine. Randomization for the study was stratified by screening plasma HIV-1 RNA levels gt or lt 100,000 copies/mL (high or low viral loads). The excess virologic failures occurred within the high viral load stratum. The estimated hazard ratio for cumulative virologic failure in this stratum was 2.33 (95 CI 1.46, 3.72), log-rank test p-value0.0003. The DSMB also noted that subjects within this stratum who received abacavir lamivudine had significantly higher rates of protocol-defined safety endpoints including higher Grade 3 fasting lipids and general body aches.
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DAD and ACTG 5202 Familiar to Most
Most underwhelmed by the findings, suggest
minimal impact.
DAD and ACTG 5202 Clinical Data Awareness

• Opinions on Data Presented
• Insufficient data (29)
• Changes prescribing behavior (12)
• Need to assess patient CV risk (6)
• Not enough to change behavior (6)

of Respondents
Q28. Is this the first time that you have seen
these data? Q29. What is your opinion of these
data?
n50
38
Abacavir Used in One Quarter of Patients
Didanosine rarely used (6).
HIV Patients on Didanosine or Abacavir Containing
Regimens
of Patients
Q30. What percentage of your patients are
currently on a didanosine or abacavir containing
regimen?
n50
39
One in Four At Risk Patients on Abacavir Will Be
Switched
22 on abacavir are at risk for MI.
HIV Patients on Didanosine or Abacavir at Risk of
MI and Who Will Be Switched to Truvada
of Patients
Q31. Of your patients on a didanosine or abacavir
containing regimen, what percentage are at risk
for MI? What percentage of these patients at risk
for MI do you plan to switch to a Truvada
containing regimen?
n50
40
One Third Have High Viral Load
HIV Patients with High Viral Load
of Patients
Q32. What percentage of your HIV patients have a
high viral load (gt100,000 copies/mL) at baseline?
n50