A review of a case study involving whether it would be proper to authorize the use of a drug whose approval had been withdrawn when it is believed to be the only hope for a dying child.

1. Presenter: Michael A. Swit, Esq., Vice President
Ethics in Clinical Trials Conference
San Diego, California
March 3, 2011
Special Challenges in Clinical Trials
Case Study: The Dying Child and
the Newly-Unapproved Drug

2.  Background: Mylotarg (gemtuzumab ozogamicin) –
approved by FDA under its “Accelerated Approval”
policy in 2000 for Acute Myeloid Leukemia (AML)
 Surrogate endpoint -- response rate (i.e., the percentage of
patients whose leukemia decreased or disappeared in
laboratory tests) -- observed in 142 patients with AML across
three clinical trials.
 Condition of approval – do study whether adding Mylotarg to
standard chemotherapy showed improvement in clinical
benefit (survival time) to AML patients.
The Scenario
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3.  Study results –
 no improvement in clinical benefit was observed
 a greater number of deaths occurred in the group of patients who
received Mylotarg compared with those receiving chemotherapy
alone.
 At initial approval, Mylotarg was associated with a serious liver
condition called veno-occlusive disease, which can be fatal.
 This rate increased in the postmarket setting
 2010 – Wyeth/Pfizer withdrew from market
 Existing supplies not recalled; patients on medication allowed to
continue
 Future use – FDA said had to be under an Investigational New
Drug (IND)
Scenario …
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4.  What FDA said about future use:
“As a result of the withdrawal, Mylotarg will not be
commercially available to new patients. Patients who are
currently receiving the drug may complete their therapy
following consultation with their health care professional.
Health care professionals should inform all patients receiving
Mylotarg of the product’s potential safety risks.
Following the withdrawal, any future use of Mylotarg in the
United States will require submission of an investigational
new drug application to FDA.”
Scenario …
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5.  The “Hypothetical” (this actually happened)
 Four-year old girl with potentially terminal cancer
 Would die in matter of days
 Doctor wants to try Mylotarg
 Hospital pharmacy – still has Mylotarg on shelves
 Girl not previously on Mylotarg
 Questions:
 Can doctor prescribe?
 Can hospital pharmacy dispense?
 Does an IRB need to get involved?
 Do we need FDA IND approval?
 If so, how?
 What are the risks?
 What would you do?
Scenario …
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6.  Prescribing
 Matter of state law
 FDA does not regulate practice of medicine
 Informed consent – needed?
 Research based consent needed -- is this research?
 Yes?
 No? –
 where is the goal of generalizable knowledge?
 As to the procedure even if not experimental?
 Yes –
 But, can this ever be informed under these circumstances that the
child is going to die anyway?
Question – Can The Doctor Prescribe?
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7.  Practice of pharmacy
 Matter of state law
 FDA (claims) says it does not regulate
 Issues
 The drug is now “unapproved”
 But, FDA approval here may be irrelevant because
 Product, when shipped in interstate commerce was lawful
 No technical prohibition on dispensing an unapproved drug that
was originally received legally (because it was approved at that time
Question – can the Pharmacy Dispense?
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8.  Caveat – I have no idea whether the hospital here had
internal procedures that might impact this even if we
conclude that an IRB approval is not needed
 Factors:
 Is this research?
 Even if research, how fast can the IRB assemble and consider
the issue?
 If not fast enough, can the IRB act by an “abbreviated” process?
Question – Does the Hospital IRB Need to
Approve?
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9.  FDA statement on future use of Mylotarg: “Following
withdrawal, any future use of Mylotarg will require
submission of an investigational new drug application …”
 Do you have time to file an IND?
 Does not matter – FDA has a mechanism to handle:
“In an emergency situation, the request to use the drug may be made via
telephone or other rapid means of communication, and authorization to ship
and use the drug may be given by the FDA official over the telephone. In
these situations, known as emergency INDs, shipment of and treatment with
the drug may begin prior to FDA’s receipt of the written IND submission
that is to follow the initial request.”
Source:
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/App
rovalApplications/InvestigationalNewDrugINDApplication/ucm107434.htm
 Note: FDA says you need IRB approval, but treatment can
begin as long as IRB is notified within 5 working days
Question – do we need FDA “approval”?
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10. So, what would you do?
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11. We contacted the FDA the next morning regarding the need for an IND. They
confirmed that because the drug was on our shelf (specifically as it was obtained
when it was approved, not recalled and not expired), we did not need an IND at
this point- even for a new patient (which is contrary to their statement of market
withdrawal indicating all new use needed an IND). They stated that once our
supply was exhausted however, we would then need to obtain an IND to
continue the treatment as the drug would need to be shipped (which again is a
little different than the statement of market withdrawal as at that point, this case
would not be a “new” patient but one “currently receiving the drug”). This
seems to confirm our discussion that the real deciding issue on the necessity of
the IND is if it is being shipped through interstate commerce. The FDA has a
dedicated person to Mylotarg due to its regulatory history/status and they
continue to receive a number of IND requests, which they state they grant
routinely.
What happened here … they called FDA
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12. About Your Presenter
Michael A. Swit, Esq.
Vice President
The Weinberg Group Inc.
Cardiff by the Sea, CA
+1 760.452.6568
+1 760.815.4762 (cell)
+1 760.454.2979 (fax)
michael.swit@weinberggroup.com
Michael A. Swit has been addressing critical FDA legal and regulatory issues
since 1984. His expertise includes product development strategies, compliance
and enforcement initiatives, recalls and crisis management, FDA regulatory
activities, labeling and advertising, and clinical research efforts. Mr. Swit
develops and ensures the execution of a broad array of regulatory and other
services to clients, both directly and through outside counsel.
Mr. Swit has been tackling critical FDA legal and regulatory issues since 1984.
His multi-faceted experience includes serving for three and a half years as
corporate vice president, general counsel and secretary of Par Pharmaceutical,
a publicly-traded, generic drug company and, thus, he brings an industry and
commercial perspective to his work with FDA-regulated companies. He then
served for over four years as CEO of FDAnews.com, a premier publisher of
newsletters and other specialty information products for the FDA-regulated
community. His private FDA regulatory law practice included service as
Special Counsel in the FDA Law Practice Group in the San Diego office of
Heller Ehrman White & McAuliffe and with the FDA practice at McKenna &
Cuneo, both in the firm’s D.C. and San Diego offices.
Mr. Swit has lectured and written on a variety of subjects relating to FDA law,
regulation and related commercial activities and is a former member of the
Food & Drug Law Journal Editorial Board. He earned his A.B., magna cum laude,
with high honors in history, from Bowdoin College and his law degree at
Emory University School of Law. He is a member (inactive) of the D.C.,
Virginia and California bars.
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