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Biotech / Medical : Vertex Pharmaceuticals (VRTX)
VRTX 467.46+1.4%3:59 PM EST
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To: Miljenko Zuanic who wrote (325)10/4/1999 8:55:00 AM
From: Casaubon  Read Replies (1) of 1169
 
you are right to take a consevative approach to any potential new drug.

MPA interact with NAD-cofactor:IMP-substrate complex, non-nucleoside and noncompetitive inhibition. Similar inhibitory mechanisms have 497. The
question is can this drug interfere with other mechanisms where NAD-cofactor is involved?

The major toxicities associated with MPA arise from a metabolism issue. The phenolic moiety on the aryl ring becomes glucuronidated and the metabolite accumulates in the gut. The accumulation acts as a slow release mechanism (very simplistic anaology) and causes destruction of the gut lining, because those cells turn over very rapidly. The inhibitory nature of MPA prevents the gut cells to be replaced and leads to the gastro-intestinal difficulites seen with MPA.

Ribavirin is a nucleoside analog, and can be expected to show toxicitites associated with those broad drugs.

VX-497 was designed to circumvent the tox issues I just discussed. That does not mean it won't have tox issues, just that it should not have tox similar to the competition.
Of course, if there is a mechanistic tox associated with t-cell inhibition ALL drugs designed to target thier inhibtion will exhibit that general tox. I don't know. Also, one can never anticipate any problems a drug will experience in the clinic so anything can happen. In my opinion, VX-497 will have different problems than the ones you have discussed, if it has any problems at all.
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