David M. Shlaes Anti-infectives Consulting, LLC Stonington, CT

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David M. ShlaesAnti-infectives Consulting,
LLCStonington, CT

• Participation sponsored by
• Nabriva, Vienna, AU
• Novexel, Romainville, FR
• Consulting relationships with a number of
  biotechnology companies or investment firms
  working in the area of antiinfective discovery
  and development.

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PERSPECTIVES

• In the consideration of risk-benefit for
  antibacterials, the agency could reflect on drugs
  approved previously (including generics) based on
  efficacy data which, in retrospect, are
  questionable.
• Antibiotics with relatively low risk, but for
  which the prescription volume is high (esp.
  generics) may be associated with higher absolute
  risk.
• Severe hepatotoxicity is not the only potentially
  life threatening adverse effect in the antibiotic
  world.

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The Dilemma for Physicians and Patients

• Essentially no antibiotic has been developed
  based on placebo-controlled trials with
  bacteriology for ABS including the 1st choice
  Augmentin or Amoxicillin.
• 2nd line antibiotics have issues.
• Macrolides resistance which leads to clinical
  failure.
• Tetracyclines widespread resistance.
• SXT common allergic reactions.
• (Fluoroquinolones, others?)
• Do we no longer need more options?

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The Numbers Ketek vs. Drug of 1st Choice in ABS

• 10 million prescriptions for Ketek were surveyed
  in response to reports of serious but rare liver
  toxicity and death.
• The FDA has identified 12 cases of acute liver
  failure among the10 million courses of therapy
  (including 4 deaths).
• Based on the rate of fatal anaphylaxis for
  penicillin, among the 10 million courses of
  therapy as surveyed for Ketek we could expect 100
  to 285 deaths from acute anaphylaxis if the
  prescriptions had been for a penicillin.
• Even if we reduce the anaphylaxis numbers by 10X
  to account for poor reporting the event is
  still more common than fatal hepatoxicity due to
  Ketek.

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US Prescription Data 2005
Antibiotic US Prescriptions (MM) US Prescriptions (MM)
Pen-VK 10.3
Azi 39.2
Ery 7.8
Clari 6.9
Ketek 3.4
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Logical Conclusions

• FDA Should Withdraw the Penicillins as therapy
  for ABS (and AECB).
• Congress should inquire as to why the FDA did not
  act more expeditiously against the penicillins.
• The problem with argumentum ad absurdum is that
  sometimes one finds the absurdity valid.
• If we want efficacious new antibiotics for
  infections caused by resistant bacteria, we must
  be realistic (and consistent!) about the risks we
  are willing to take and the standards we impose.