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Biotech / Medical : Vertex Pharmaceuticals (VRTX) -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (318)	9/28/1999 12:03:00 AM
From: Miljenko Zuanic	Read Replies (1) \| Respond to of 1169

Rick: All in all, it appears to me that amprenavir do compare well with older PIs in potency with some improvement in resistance profile and metabolic side effects. Said this, and add GLX marketing experience for AIDS market it isn't impossible that amprenavir gain nice worldwide market share, at least for salvage therapy. I guess this will partialy eliminate WS concern about VRTX first drug performance and maybe start to look beyond what is in house. By no means I am expert for viral infection, so this may well be my BS. More important is that VRTX investment thesis is much more than amprenavir or pro-amprenavir. Also, one should keep in mind that GLX is fully responsible for finance of this projects, so no negative impact on VRTX balance shits. Only possible positive from amprenavir royalty. Post: Message 11350516 actually describe NIH and WHO growing concern (presented also in many press-news recently) about spread of the HCV and limited therapy option. Also, it is known than significant HIV positive population is also HCV positive. In this light recent in vitro study and first indication of efficiency in real word indicate new opportunity for new and more potent IMPDH inhibitor. So far VX-497 did show that it is more superior than anything on market or in trial. If this hold in late stage clinical trials and without side effects, HCV/HIV pts may have new treatment option in near future. Mycophenolic Acid Shows Powerful Synergistic Anti-HIV Activity With Abacavir -------------------------------------------------------------------------------- By Deborah Mitchell WESTPORT, Aug 19 (Reuters Health) - Abacavir, the first clinically available guanosine analogue HIV-1 reverse transcriptase inhibitor, used in combination with mycophenolic acid, results in a potent and synergistic inhibition of HIV-1 replication in vitro "...to an extent not previously observed with other antiretroviral combinations." "The use of inhibitors of purine nucleoside metabolism has been advocated for the treatment of HIV-1 infection," Dr. David Margolis, of the University of Maryland Institute of Human Virology in Baltimore, and colleagues explain. Mycophenolic acid, which is used in organ transplantation, is a specific inhibitor of lymphocyte proliferation via blockade of purine synthesis. Specifically, this agent "...acts on inosine monophosphate dehydrogenase to block conversion of inosine monophosphate to guanosine monophosphate." "Because of the antiviral potency of abacavir and the lymphocyte specificity of [mycophenolic acid], we hypothesized that these drugs might synergize in the inhibition of HIV replication without causing substantial cellular toxicity." Overall, the combination of these two drugs in vitro was "...exceedingly potent and synergistic," the researchers report in the August 15th issue of the Journal of Acquired Immune Deficiency Syndromes. The antiviral activity of abacavir was "greatly enhanced" by low concentrations of mycophenolic acid in activated peripheral blood mononuclear cells and monocyte-derived macrophages. "This effect was also seen when primary clinical isolates were used." Dr. Margolis' team also found that this combination was active against an HIV-1 strain that encoded the M184V mutation. "However, the combination of [mycophenolic acid] and zidovudine (ZDV) or stavudine (d4T) was antagonistic," they note. "These are laboratory studies," Dr. Margolis told Reuters Health, "...and the clinical implications need to be carefully tested in clinical trials." It would be "unfortunate" if this drug combination were used before clinical data are available, he said. Dr. Margolis emphasized that because the "...antinucleoside drug is targeted to the cell, not the virus," there would probably be "...inescapable side effects or toxicities with some patients." However, he envisions two possible treatment scenarios "...using this combination or similar combinations that use the same strategy." The first would be "...to augment the effectiveness of a drug in standard therapy before significant clinical drug resistance was established." The other use might be in established drug resistance, he continued. "Preliminary data show that this combination is highly effective against multinucleoside-resistant viruses." This salvage therapy approach is currently being pursued at the University of Maryland in a small, uncontrolled pilot study with "...patients who essentially have no other viable therapeutic options." The patients have only been on therapy for a few weeks, Dr. Margolis explained, but the "...very, very early results are somewhat encouraging." J Acquir Immune Defic Syndr 1999;21:362-370.