Myelodysplastic Syndrome Discussion

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Myelodysplastic Syndrome Discussion

• 16 January 2006

Prepared by MedPanel, Inc.

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Myelodysplastic Syndrome Discussion
Outline

• Project Objectives
• MedPanel Methodology Panelists
• Major Takeaways
• Detailed Findings
• Conclusions

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Project Objectives MedPanel Methodology
Panelists Major Takeaways Detailed
Findings Conclusions
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Project Objectives

• Convene online focus group of hematologist-oncolog
  ists (heme-oncs) experienced in treating MDS
• Gather feedback from this group regarding
  recently introduced upcoming products
• Vidaza (azacitidine), FDA-approved 5/04
• Dacogen (decitabine), pending FDA approval
• Revlimid (lenalidomide), pending FDA approval
• Explore alternative indications and/or patient
  populations/sub-types
• Determine impact of products on current
  marketplace (immediate and 6-month perspective)

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Project Objectives MedPanel Methodology
Panelists Major Takeaways Detailed
Findings Conclusions
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MedPanel MethodologyPanelist Recruitment
We recruited based on a specific set of screening
criteria developed
Proprietary Database
Screening Criteria

• Hematologist-oncologists (n6)
• All panelists must be
• In practice 2-25 years
• Panel average 12 years
• Spending gt 75 time in clinical practice
• Panel average 93
• Treating a gt 10 MDS patients per month
• Panel average 22 patients/month

Outside the Database
Simultaneous discussion guide development
panelist recruitment

• Asynchronous, threaded discussion
• Panelists respond anonymously

• Questions posed by physician moderator to expand,
  probe, or clarify responses as necessary

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MedPanel MethodologyPanelist Details
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Project Objectives MedPanel Methodology
Panelists Major Takeaways Detailed
Findings Conclusions
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Major TakeawaysTreatment of MDS Patients
Treatment by patient risk-group

• Low-risk MDS patients are typically offered
  supportive care with transfusions of pRBC or
  platelets
• Intermediate-risk MDS patients receive supportive
  care with transfusions with or without
  chemotherapy
• Most high-risk MDS patients are treated with
  Vidaza monotherapy
• Patient age, PS, and IPSS-defined risk category
  help to determine which treatments are given
• Decreased progression of disease and improvement
  in toxicity measures are the most important
  product attributes for treatment of MDS
• Other important attributes include control of
  symptoms and improvement in quality of life and
  efficacy measures
• Most panelists expressed minimal satisfaction
  with the performance of current MDS treatments on
  the important product attributes
• The major unmet needs for treatment of MDS are
  the low treatment response rates and the lack of
  a cure

Key product attributes needs
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Major TakeawaysRole of Vidaza Dacogen
Vidaza

• Currently administered to in the outpatient
  setting at 75 mg/m2 per day for seven consecutive
  days every 28 days for 4 to 8 cycles or as long
  as beneficial
• Discontinued in up to 50 of patients most often
  due to unmanageable side effects, usually after
  2-3 cycles
• Major strengths include FDA approval, outpatient
  administration, prolonged survival, and
  improvement in quality of life
• Weaknesses include high cost, low response rates,
  no significant improvement in overall survival,
  myelosuppression, inconvenient administration,
  and short duration of response
• Major strength is the high treatment response
  rate
• Compared to Revlimid, its main advantage is that
  it is indicated for all MDS patients, not a
  subset
• Major weakness is its toxicity (myelosuppression)
• Compared to Revlimid its main disadvantages are
  that Dacogen is more toxic and is delivered
  intravenously

Dacogen
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Major TakeawaysRole of Dacogen Revlimid
Dacogen use drivers

• Dacogen is likely to be used primarily in
  high-risk MDS patients in the outpatient setting
  at a daily dose of 10 mg/m2 administered
  subcutaneously
• The major barrier to the adoption of Dacogen is
  lack of FDA approval a better dosing schedule
  would facilitate the acceptance and use of
  Dacogen
• Major strengths are its efficacy in patients with
  5q- syndrome and oral administration
• Major weaknesses include patient compliance,
  reimbursements issues, and added toxicity
• Barriers to the adoption of Revlimid include
  cost and reimbursement issues, side effects, and
  lack of clinical evidence
• While oral Revlimid would be used primarily in
  patients with 5q- syndrome, the majority of
  panelists would also consider it for patients
  with non 5q- disease
• Additional evidence of activity in patients with
  5q- syndrome, low cost, patient assistance
  programs, and availability of samples would
  facilitate Revlimids acceptance and use

Revlimid
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Major TakeawaysOther Key Issues
Details on 5q-

• Between 10 and 50 of panelists MDS patients
  are low-risk patients with non 5q- disease and up
  to 50 are high-risk patients with 5q- syndrome
• Patients with 5q- syndrome are currently defined
  by chromosome and cytologic analyses
• Reimbursement has a strong impact on therapy
  choices for the majority of panelists, however,
  none have had significant reimbursement issues
  for MDS
• Use of Revlimid for MDS treatment will be
  reimbursement-dependent, whether it is priced at
  4000 or 6000 per month.
• Aranesp, thalidomide, and arsenic trioxide will
  impact the MDS pharmaceutical marketplace, while
  Telintra, tipifarnib, and amifostine are not
  expected to have an impact
• Only one panelist was aware of products in
  development that would compete with Dacogen and
  Revlimid
• These include the liposomal form of TLKI-199,
  SCIO-469, tipifarnib, lonafarnib, and bryostatin-1

Cost reimbursement
Other potential MDS treatments
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Major TakeawaysFuture Treatment Patterns
Treatment landscape in 6 months

• In the next 6 months, the use of Dacogen and
  Revlimid is expected to increase while Vidaza
  will begin to decline
• Dacogen will meet unmet needs for the treatment
  of transfusion-dependent patients, while Revlimid
  will meet unmet needs for the treatment of
  patients with 5q- syndrome
• Dacogen will be used first-line for the majority
  of MDS patients, except for those with 5q-
  syndrome where Revlimid would be the treatment of
  choice
• The majority of panelists feel that Revlimid and
  Dacogen will not completely replace Vidaza
  although they will limit its use to a second-line
  treatment
• The ideal Vidaza patient will be those unable to
  tolerate Dacogen

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Major TakeawaysFollow-Up Survey Results

• Between 20 and 60 of panelists MDS patients
  are high risk
• Between 40 and 80 are low risk
• In one year, Dacogen use is expected to increase
  most in high risk patients while Revlimid will
  increase in both patient categories

High Risk Patients Current Expected Treatment
Low Risk Patients Current Expected Treatment
Average Percent of Patients Currently Treated or
Expected to be Treated in One Year
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Project Objectives MedPanel Methodology
Panelists Major Takeaways Detailed
Findings Conclusions
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Detailed FindingsCurrent Treatment of MDS
Both low- and intermediate-risk MDS patients are
usually offered supportive care with transfusions
of pRBC (packed red blood cells) or platelets

• Other treatment strategies for low-risk patients
  include
• Growth factors / Cytokines
• Procrit or Aranesp
• Observation

• Other treatment strategies for intermediate-risk
  patients include
• Growth factors / Cytokines
• Chemotherapy (Vidaza monotherapy)

• Most high-risk MDS patients are treated with
  Vidaza monotherapy
• Other treatment strategies for high-risk patients
  include
• Supportive care with prn transfusions of pRBC or
  platelets
• Growth factors / Cytokines
• Bone marrow transplantation
• Intensive chemotherapy (combinations and high
  doses)

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Detailed FindingsImportant Therapy Attributes

• Decreased progression of disease and improvement
  in toxicity measures are the most important
  product attributes for treatment of MDS
• Other important product attributes include
• Control of symptoms
• Improvement in quality of life measures
• Ease of administration
• Improvement in overall survival
• Minimal risk of cytopenia
• Decreased need for transfusion
• Minimal risk of infection
• Cost

• The panelists are dissatisfied with current MDS
  treatments performance on important product
  attributes
• Improving, but a long way to go
• Effective, but supportive in nature

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Detailed FindingsUnmet Needs

• The major unmet needs for treatment of MDS are
  the lack of a cure and the low response rates
  associated with current treatments
• Other unmet needs include
• High costs
• High toxicity rates
• Continued need for transfusion
• Short time to progression
• Increased risk of infection
• Inconvenient administration requirements

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Detailed FindingsMeeting Unmet Needs

• New products will meet some important unmet needs
  in select patient segments
• Vidaza
• Transfusion-dependent patients
• Dacogen
• Transfusion-dependent patients
• Revlimid
• Patients with 5q- syndrome
• Patients with low/Int-1 IPSS scores

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Detailed FindingsStrengths Weaknesses of Vidaza

• Strengths of Vidaza include
• FDA approved
• Outpatient administration
• Prolonged median survival time
• Decreased risk of AML transformation
• Decreased need for transfusion
• Improvement in quality of life measures

• Weaknesses of Vidaza include
• High cost
• Low response rates
• 7 day treatment requirements
• No significant improvement in overall survival
• Myelosuppression
• Not curative treatment
• Inconvenient administration
• Short duration of response

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Detailed FindingsUses of Vidaza

• Vidaza is currently administered to MDS patients
  in the outpatient setting at 75 mg/m2 per day for
  seven consecutive days every 28 days for 4 to 8
  cycles
• Vidaza could also be used for the following
  patients
• High-risk patients
• Patients refractory to growth factor and
  cytokine treatment
• Patients progressing to intermediate- and
  high-risk status
• Patients in lower risk groups requiring multiple
  transfusions

• Vidaza is administered for as many cycles as the
  patient benefits and is discontinued due to
  unmanageable side effects
• Reasons for continuing Vidaza treatment include
• I give as long as improvement seen even if more
  than 4 cycles.
• Complete response may require more than four
  cycles.
• May take more than 4 cycles to see efficacy.
• or to best RR.

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Detailed FindingsStrengths Weaknesses of
Dacogen

• The major strength of Dacogen is its high
  treatment response rate
• Other strengths include
• Strong cytogenetic response
• Prolonged median survival time
• 5 day or once per week dosing schedule

• The major weakness of Dacogen is its toxicity,
  particularly myelosuppression (pancytopenia)
• Other weaknesses include
• Inpatient administration
• Lack of FDA approval
• Lack of clearly defined treatment regimen (dosing
  and administration)

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Detailed FindingsBarriers Facilitators for
Dacogen

• The major barrier to the adoption of Dacogen is
  lack of FDA approval
• Other barriers include
• Toxicity concerns
• Reimbursement issues
• Inconvenient dosing schedule
• Lack of clearly defined treatment recommendations

• A better dosing schedule would facilitate
  acceptance and use of Dacogen
• Other facilitators include
• Clinical evidence of efficacy (from large-phase
  III clinical trials)
• Improved toxicity profile

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Detailed FindingsUses of Dacogen

• Dacogen is likely to be used primarily in
  high-risk MDS patients in the outpatient setting
  at a daily dose of 10 mg/m2 administered
  subcutaneously
• Dacogen also could be used in the following
  patients
• Patients with intermediate 1-2 IPSS scores
• Patients refractory to growth factor treatment
• Revlimid non-responders
• Vidaza non-responders

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Detailed FindingsStrengths Weaknesses of
Revlimid

• Strengths of Revlimid include
• High response rates in patients with 5q- syndrome
• Oral administration
• Decreased toxicity and equivalent efficacy to
  thalidomide

• Weaknesses of Revlimid include
• Low patient compliance
• Reimbursement issues
• Toxicity
• Neutropenia
• Neuropathy
• Constipation
• Fatigue
• Hypercoagulation
• Bone marrow toxicity

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Detailed FindingsBarriers Facilitators of
Revlimid

• Barriers to the adoption of Revlimid include
• Cost
• Lack of FDA approval
• Lack of clinical evidence
• Reimbursement issues
• Myelosuppression in cytopenic patients
• Hypercoagulation
• Small target patient population
• Low patient compliance

• Acceptance and use of Revlimid would be
  facilitated by
• FDA approval
• Strong evidence of activity in patients with 5q-
  syndrome
• Oral administration
• Low cost
• Availability of samples
• Patient assistance programs
• Additional clinical data

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Detailed FindingsUses of Revlimid

• Oral Revlimid would be used primarily in patients
  with 5q- syndrome
• Revlimid also could be used in the following
  patients
• Patients with low/intermediate-1 IPSS scores
• High-risk patients
• Patients who refuse intravenous or subcutaneous
  treatment
• Patients requiring second- or third-line of
  treatment

• Most panelists would use Revlimid in patients
  with non 5q- disease
• till data says not to since there are no good
  drugs available and Revlimid appears to be
  non-toxic.
• as there is still some response in Low/Int-1
  IPSS scores patients
• should be well-tolerated in these patients.

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Detailed FindingsDacogen vs. Revlimid

• The main advantage of Dacogen compared to
  Revlimid is that Dacogen is indicated for all
  patients with MDS
• Other advantages include
• Increased patient compliance with intravenous
  administration
• Decreased reimbursement issues with intravenous
  administration
• No hypercoagulation
• Higher response rate

• The main disadvantages of Dacogen compared to
  Revlimid are increased toxicity and intravenous
  administration
• Other disadvantages include increased
  myelosuppression

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Detailed FindingsPatient Subtypes

• Familiarity with published clinical data from the
  New England Journal of Medicine as well as data
  submitted to the FDA influence the panelists use
  of Revlimid
• Use in low-risk patients with non 5q- disease
• depending upon patient motivation, availability
  and insurance.
• Use in high-risk patients with 5q- syndrome
• I will use as first line.
• up front in early stage disease.

• Patients with 5q- syndrome are defined by
  chromosome analysis and cytology
• Between 10 and 50 of the panelists MDS
  patients are low risk with non 5q- disease
• Between 0 and 50 of the panelists MDS patients
  are high risk with 5q- syndrome

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Detailed FindingsReimbursement Cost Issues

• Physicians have not encountered any reimbursement
  issues to date for MDS treatments, however,
  reimbursement does strongly impact their therapy
  choices
• Representative comments include
• The cost threshold is not my concern, it is for
  the patient and their payers to decide.
• I do not give any chemo in the office if there
  is a loss. I will still give the proper chemo
  but in the hospital clinic.
• There is no specific number, the criteria for
  use, no matter what the cost is. If no
  reimbursement, then no treatment in the office.
  If reimbursed and it is the best for the patient,
  then it would be given no matter what the cost.
• Of course cheaper the drug then its better for
  hospitalif patient does not have to pay out of
  pocket cost then cost would have minimal impact
  as long as this drug is indicated clearly and
  used appropriately.
• In a situation where cure is not possible
  w/multiple options I discuss all w/the patient.
  Some will decide on the best copay.

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Detailed FindingsNovel MDS Treatments

• New and existing agents will impact the adoption
  and use of Dacogen and Revlimid
• Novel agents
• Liposomal formulation of TLK-199
• SCIO-469
• Tipifarnib
• Lonafornib
• Bryostatin-1
• Existing agents
• Aranesp
• Thalidomide
• Arsenic

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Detailed FindingsFuture Treatment of MDS

• In the next 6 months, there will be increased use
  of Dacogen for the treatment of MDS
• Other anticipated changes include
• Increased use of Vidaza, Revlimid, and Dacogen
  as opposed to supportive care
• Increased patient selectivity when utilizing new
  drugs
• More treatment options
• New combinations of novel and existing drugs
• Higher treatment response rates
• Increased use of Vidaza in overall MDS patient
  population

• Revlimid/Dacogen probably will not completely
  replace Vidaza
• The majority of panelists believe Vidaza will not
  be replaced
• I do not think either Revlimid or Dacogen will
  replace Vidaza completely but Vidaza can still be
  used as 2nd, 3rd, or lower line when the others
  fail to work.
• A small number believe Vidaza may be replaced
  within 2 years

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Detailed FindingsIdeal Use of Dacogen Revlimid

• Dacogen will be used for the majority of MDS
  patients, not including those with 5q- syndrome
• Other candidates include
• High-risk patients
• Patients who have relapsed or are refractory to
  other treatment

• Patients with 5q- syndrome are the ideal
  candidates for Revlimid treatment
• Other candidates include patients with non 5q-
  disease as second-, third-, and fourth-line
  treatment

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Project Objectives MedPanel Methodology
Panelists Major Takeaways Detailed
Findings Conclusions
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Conclusions

• Decreased progression of disease and increased
  tolerability are the most important attributes
  when selecting a treatment for MDS
• Most panelists are not satisfied with the
  products currently available to treat MDS due to
  low treatment response rates and high toxicity
  rates
• Although there are currently no reimbursement
  issues with MDS treatment, reimbursement is
  essential and requires FDA approval
• Additional clinical evidence and/or FDA approval
  would increase the use and adoption of both
  Dacogen and Revlimid
• Dacogen will meet unmet needs for the treatment
  of transfusion-dependent patients Revlimid will
  meet unmet needs for patients with 5q- syndrome
• In the near future, the use of Dacogen for the
  treatment of MDS is expected to increase,
  especially in high-risk patients
• Revlimid use also is expected to increase,
  especially among 5q- patients
• Vidaza use will continue, although it may be
  reserved for second- or later-line treatment