Download Phase 2 - Philadelphia University

Birth defects
caused by use of thalidomide
Example: Thalidomide
From 1956 to 1962, approximately 10,000 children were born with
severe malformities, including phocomelia, because their mothers had
taken thalidomide during pregnancy. In 1962, in reaction to the tragedy,
the United States Congress enacted laws requiring tests for safety
during pregnancy before a drug can receive approval for sale in the U.S.
O
N
O
NH
O
O
Thalidomide
Phocomelia presents at birth very short or absent long bones
and flipper-like appearance of hands and sometimes feet.
Example: Thalidomide
•Researchers, however, continued to work with the drug. Soon
after its banishment, an Israeli doctor discovered antiinflammatory effects of thalidomide and began to look for uses
of the medication despite its teratogenic effects.
•He found that patients with erythema nodosum leprosum, a
painful skin condition associated with leprosy, experienced
relief of their pain by taking thalidomide.
Teratogenic = Causing malformations in a fetus
Thalidomide
Further work conducted in 1991 by Dr. Gilla Kaplan at Rockefeller
University in New York City showed that thalidomide worked in
leprosy by inhibiting tumor necrosis factor alpha. Kaplan partnered
with Celgene Corporation to further develop the potential for
thalidomide.
Subsequent research has shown that it is effective in multiple
myeloma, and it is now approved by the FDA for use in this
malignancy. There are studies underway to determine the drug's
effects on arachnoiditis, Crohn's disease, and several types of
cancers.
Clinical Trials
• Phase I: Drug is tested on healthy volunteers
to determine toxicity relative to dose and to
screen for unexpected side effects
Clinical Trials
• Phase II: Drug is tested on small group of patients
to see if drug has any beneficial effect and to
determine the dose level needed for this effect.
Clinical Trials
• Phase III: Drug is tested on much larger
group of patients and compared with existing
treatments and with a placebo
Clinical Trials
• Phase IV: Drug is placed on the market and patients
are monitored for side effects