Tom, I was wondering what Barron's would say. Thanks in advance!
healthcg.com
The "take-home messages" from this session on the final day of ICAAC, from Dr. Joel Gallant in the article above: "Dual Protease Inhibitor Therapy: The Agony and the Ecstasy" are:
1. RTV/SQV is highly effective and durable when used in PI-naive patients.
2. RTV/SQV is not very effective as salvage therapy after patients have failed RTV or indinavir (IDV).
3. RTV/SQV may be more likely to work after IDV failure if the switch is made early, but support for this approach remains either hypothetical or anecdotal.
4. RTV/SQV appears to be more effective in patients with nelfinavir (NFV) resistance than IDV resistance, although the durability of the effect remains to be determined. This finding, if it is borne out in long-term follow-up, offers very preliminary support for the suggestion, based on genotypic resistance patterns, that NFV-resistant virus may be more treatable than IDV-resistant virus.
RTV-Ritonavir=Norvir (Abbot);
SQV-Saquinavir=Invirase (hgc) or Fortonase-sgc (Roche);
NLF-Nelfinavir-Viracept (Agouron);
IDV-Indinavir-Crixivan (Merck)
At present, the current recommendations and treatment guidelines of the International AIDS Society, in a Concensus Statement made on on June 25, 1997 remain and they recommend dual protease inhibitor therapy only after failure of triple drug therapy.
The recommendations at present include a three-drug regimen of 2 nucleoside analog reverse transcriptase inhibitors (NRTIs) and a protease inhibitor with strong in vivo potency. -indinavir, ritonavir, nelfinavir.
Gallant was hopeful in the studies by Dr. Henry showing that those who failed Viracept can respond to RTV/SQV. Dr. Henry's studies are discussed and it is concluded that a significant proportion of patients experiencing NFV failure will respond to RTV/SV. In Agouron's study 506/511, of 12 viracept resistant patients, all 12 had viral loads drop below 500, and at 16 weeks, 6/7 were undetectable. In study 525, 3 of 7 viracept resistant, heavily pretreated with up to 5 prior drug treatments, responded favorably. Two of those who failed had sub-therapeutic levels of the drugs, i.e., they were not adequate doses of medication. Furthermore, prior to switching therapies, 2 patients in the above studies had mutations associated with SQV resistance.
What has all this fuss been about? We can thank thestreet.com for their over zealous attention given to a small inconclusive study by Torres from St. Vincents Hospital.
This study is not even mentioned or included in Dr. Gallant's conclusions on the final day of ICAAC.
I wonder why Jesse provide information in the same article on the stock price and belief of the shorts of other companies like Vertex, Gilead, Roche, Merck, Glaxo, or Abbot?
In the same link given above, Dr. John Mellor gives an excellent review of Dual Protease Inhibitor Therapy.
He valuates each combination based on how well it meets the goals of dual-PI therapy. At present RTV/SQVhgc is the most extensively studied and most widely used.
Data is presented on interactions between PI's that have been tested as well as ongoing trials for the following combinations:
RTV/SQVsgc; RTV/NFV; RTV/IDV; IDV/NFV;NFV/SQV/sgc;
The Spice Study is to be presented this month at the Hamburg meetings, randomized patients to receive either
1. NFV/SQVsgc
2. NFV/SQVsgc + 2 nucleosides
3. NFV + 2 nucleosides
4. SQVsgc + 2 nucleosides
There is another ongoing trial giving 141 in the following combinations:
141/NFV; 141/IDV;141/SQVsgc.
Charles Flexner and Joe Gallant are working with investigators from Abbott and Agouron on RTV/NFV: a multidose trial (RTV 400 bid plus NFV 500 or 750 bid.
In a single dose trial, RTV increased the AUC of NFV by 2.5 fold. RTV may also accentuate the M8 metabolite of NFV possibly resulting in increased antiviral activity. The trial is in progress. |
