FDA
TALK PAPER

T97-44                      Ivy Fleischer Kupec:  301-827-6242
Sept. 22, 1997              
                            Consumer Inquiries:   800-532-4440



    FDA ISSUES APPROVABLE LETTER TO CELGENE FOR THALIDOMIDE


     On Friday, Sept. 19 the Food and Drug Administration issued
an "approvable" letter to Celgene Inc. for thalidomide as a
treatment for a leprosy complication: the skin manifestations of
erythema nodosum leprosum (ENL).  ENL is a serious, severe
complication of leprosy for which no good alternative therapies
are presently available for many people with this disease.  
     Issuance of an approvable letter is one of several
intermediate steps that can be taken by FDA during the drug
review process.  It does not mean that the drug is approved for
marketing in the United States at this time.
     This approvable letter means that the Agency has determined
that the submitted clinical data demonstrate that the benefits of
this product outweigh the known risks in the treatment of ENL
when the product is used under tightly controlled medical
supervision.  However, before a final approval decision can be
made, additional information, including the wording of the final  
labeling and the details of a restricted distribution control
system, must be submitted by Celgene and reviewed and agreed upon
by FDA.  As announced by Celgene, the company and the FDA are in
discussions at present about these further issues.
     In this approvable action, FDA, is acting under its
authority to restrict distribution of a product that presents
major safety concerns.  The letter makes clear that, if this
product reaches the stage of final approval in the United States,
it will be under the restricted distribution requirements (in
Subpart H of 21 CFR 314). 
     Thalidomide is well-known to cause severe birth defects. 
Because of this, FDA is committed to using every means possible,
including restricted distribution, to minimize the chance that
such will occur and to maximize the opportunities for health
practitioners and patients to be made fully aware of the
potential side effects of this product before they choose to use
it.  Celgene has announced that it agrees with this restricted
distribution concept: as mentioned previously, the details are
yet to be completely worked out.
     Timing of further FDA action on this application is now
dependent on Celgene's responses to the issues identified in the 
approvable letter and on the rapidity with which they and FDA can
come to agreement on these issues.
     FDA's action follows the recommendations made earlier this
month by a majority of FDA's Dermatologic and Ophthalmic Advisory 
Committee, a panel of outside experts asked to consider this
matter.
     Thalidomide is a drug originally marketed as a sedative
outside the United States from the 1950s to early 1960s, until it
was linked with severe birth defects.  In addition to causing
serious fetal deformities, thalidomide has been associated with
other adverse reactions, including peripheral neuropathy, a
disorder, that, in some patients, has resulted in permanent nerve
damage. The product has never been approved for use in the United
States.
     In the past several years, much has been learned about
thalidomide's potent ability to modify the response of the human
immune system.  By exploiting this good effect of thalidomide,
interest has risen in both the medical research community and in
many patient advocacy groups for increased testing of this
product for use in several severe diseases, like ENL, that are
mediated through the immune system and for which no other good
therapies are presently available.  
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