Subject: U. S. Expected to License Firm to Make, Test Two AIDS Drugs
Date: Published: 9/18/87 95 lines
Source:  WALL STREET JOURNAL. Copyright Dow Jones & Co. Inc. 

   Bristol-Myers Is Expected to Get License
   From U. S. to Make, Test Two AIDS Drugs
    ---
   By Marilyn Chase
   Staff Reporter of The Wall Street Journal

   The U. S. government is expected to grant an exclusive
license to Bristol-Myers Co. for the manufacture and testing
of two potentially useful drugs against acquired immune
deficiency syndrome.
   The compounds, dideoxyadenosine and dideoxyinosine, known
as DDA and DDI, kill the virus in the test tube by slipping
false building blocks into its genetic material.  The drugs
belong to the same family as Burroughs-Wellcome Co. 's
azidothymidine, or AZT, which was approved last March by the
Food and Drug Administration as the first prescription drug
for AIDS. 
   Separately, researchers said the AIDS drug,
dideoxycytidine, or DDC, is turning out to have some
unexpected toxic side effects, which are raising questions
about the drug's ultimate usefulness.
   Bristol-Myers, though prominent in the field of cancer
chemotherapy drugs, hasn't had a very high profile in AIDS
research except through its Seattle-based division, Genetic
Systems.  A spokeswoman for the New York-based pharmaceuticals
concern confirmed that it is in negotiations with the
government for the exclusive license.
   Federal scientists said the government is now negotiating
final terms of the license to include a company commitment to
moderate pricing of the drugs, should they prove effective in
future clinical trials.  Wellcome PLC, the London-based parent
of Burroughs-Wellcome, caused a furor by setting the
wholesale price for a yearly dosage of AZT at almost $8,000,
which translates to about $10,000 retail, making AZT the
costliest prescription drug in history.  Company executives
defended the price in congressional hearings, maintaining the
drug had cost $80 million to develop and manufacture.
   Because Wellcome owns AZT and didn't need a manufacturing
license, the government hadn't any direct control over its
price.  This time, however, sources said, the government holds
the patent to DDA and DDI, which were developed in the
laboratory of Samuel Broder of the National Cancer Institute.
Dr. Broder was out of the country yesterday and couldn't be
reached for comment.
   After doctors and patients decried the cost of AZT, the
government put all potential licensees on notice by
publishing licensing criteria in the Federal Register that
emphasized a company's willingness to charge "reasonable"
prices.  "The government is in a very strong position" where
it's had a central role in the drugs' development, a source
close to the negotiations said yesterday.
   The other AIDS compound, DDC, has thrown researchers a
curve by provoking unexpected nerve damage and pain in a
substantial proportion of patients.  DDC, licensed last May to
Hoffman-La Roche Inc., has been tested on about 70 patients
according to Whaijen Soo, director of anti-viral research at
the Nutley, N. J. -based pharmaceuticals company.
   DDC causes a peripheral neuropathy -- tingling, numbing
and pain, principally in the feet -- that can require potent
painkillers such as morphine.  It isn't known whether such
side effects can be reversed, Dr. Soo said.  While AIDS also
causes some neuropathy, including both discomfort and
weakness in the hands and feet, the drug's worst side effect
is the foot pain.
   The drug, like some potent anti-cancer drugs, seems to
have a cumulative dosage limit that, once reached, triggers
the neuropathy.  The main question now is whether researchers
can find a lower dose that is still effective.
   DDC suppresses the AIDS virus, as shown by a lowering of
viral protein p24 in the blood.  It also is 50 to 100 times
more powerful than previously thought, according to Dr. 
Broder, the drug's developer, in a recent interview.
Researchers at the University of Miami have found that a dose
of DDC that is 100 times lower than the AZT dose can still
suppress the virus, he added, suggesting a safe dose may be
possible.
   Another possible strategy for avoiding side effects is a
regimen of DDC and AZT on alternating weeks, now being tested
by Thomas Merigan of Stanford University and others.  Doctors
hope the low-dose combination will work without inducing
either the anemia of AZT or the pain of DDC. 
   "We may be able to get around the toxicity by lowering the
dose either alone or in combination.  (But) if we can't find a
way around the toxicity," Dr. Broder warned recently, "the
drug will die."

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