Evaluating A Systemic Therapy Psoriasis

1
Evaluating A Systemic TherapyPsoriasis

• Efficacy
• Safety
• Labeling

2
What patients want!!!

• Effective
• Clear or nearly clear is what patients want
• Keeps on working
• Patients do not wish to constantly use therapy
  when the disease returns treatment should work at
  least as well.
• Convenient- limited trips to MD
• Not messy
• Does not require much time

3
What patients want contd.

• Safe
• Does not make patient uncomfortable (or worse)
  while being used
• Safe long term / repeated use does not preclude
  or interact with other treatments

4
Psoriasis

• Psoriasis is a chronic disease (average duration
  about 50 years!!!
• Extent and impact vary greatly among patients and
  in the affected individual over time.

5
Questions for today

• Does it work?
• Does it keep working?
• Is it safe?
• Do its potential benefits outweigh its risks?

6
Does it work?

• In what types of patients has efficacy been
  demonstrated?
• How well/often does it work?
• (statistically significant is not enough)
• What are factors associated with success/failure?
• ( Do available data help select patients for
  when the drug is most effective?)

7
Does it keep working?

• Psoriasis is a chronic disease.
• If a treatment has risks, its utility depends on
• Low incidence of rebound
• Length of remission
• Efficacy (by patient criteria)

8
Is it safe?

• Short time and long term safety with use repeated
  must be assessed
• Concerns for this class
• Infection
• Cancer especially lymphoma and SCC
• Immunologically mediated diseases (LE, MS, etc).
• Immunologic reaction to the drug (I.e.
  antibodies)
• May decrease efficacy
• May be a health risk

9
Is it safe contd

• Do we have sufficient and robust data?
• Is it likely PMS will provide timely and Robust
  date? (I.e can we rely on Phase IV commitments?)

10
Do its benefits outweigh its risks?

• Short term perspective insufficient.
• A long term view is needed
• Do available data allow us to recommend approval?
• What labeling will put the drug in proper
  perspective given when we know?

11
PASI

• This meeting is not about the PASI ( or what
  percentage improvement represents significant
  clinical improvement.)
• The PASI is a flawed scale.
• We could (and have) spent many hours extolling
  its virtues and condemning its shortcomings.

12
Past Comments about the PASI at Advisory
Committee Meetings

• Dr. Joseph McGuire I think no one is satisfied
  with the clinical fidelity of PASI.
• Dr. Robert Stern Lets pass on the PASI
• (not a compliment to the PASI)
• Dr. Mark Lebwohl
• Now I entirely agree with Dr. Stern, we have to
  pass on the PASI..

13
The Literature

• Dr. Michael Bigby ( JAAD, 1996)
• The major problem with indices ( PASI) is that
  they confound area of involvement with extent of
  disease.
• Until better scales are developed trials with
  the simplest and most objective outcome variables
  are best. ( Bigby, JAAD, 1996)

14
A Proposal

• Acknowledging the limitations of the evaluation
  metrics utilized in the studies we will review
  today, let us agree to utilize the agreed upon
  two primary end points today.
• PASI 75 improvement
• Clear or almost clear
• And try not to complicate the discussion of
  this product with debate about how to measure
  psoriasis.

15
Current Labeling (Indication) of Systemic
Therapies for Psoriasis.
16
Caution Methoxsalen is a potent drug.

• Photochemotherapy (Methoxsalen with long wave UVA
  radiation) is indicated for the symptomatic
  control of severe, recalcitrant disabling
  psoriasis not adequately responsive to other
  forms of therapy and when the diagnosis has been
  supported by biopsy.

17
Soriatane

• Soriatane is indicated for the treatment of
  severe psoriasis.
• Because of significant adverse effects
  associated with its use, Soriatane should be
  prescribed only by physicians knowledgeable in
  the systemic use of retinoids.
• Methotrexate is indicated in the symptomatic
  control of severe, recalcitrant, disabling
  psoriasis that is not adequately responsive to
  other forms of therapy, but only when the
  diagnosis has been established, as a biopsy
  and/or after dermatologic consultation.

18
Neoral

• Psoriasis Neoral is indicated for the treatment
  of adult, nonimmunocompromised patients with
  severe (I.e extensive and/or disabling)
  recalcitrant, plaque psoriasis who have failed to
  respond to at least one systemic therapy.

19
Amevive

• Amevive is indicated for the treatment of adult
  patients with moderate to severe chronic plaque
  psoriasis who are candidates for systemic therapy
  or phototherapy.

20
Todays Task

• Answers FDAs questions.
• Judge if benefits outweigh Risk
• Suggest Additional Data Needs for Judging Long
  Term Role