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

To: scaram(o)uche who wrote (5322)	9/18/1998 10:59:00 AM
From: margie	Read Replies (1) \| Respond to of 6136

The side effects are not so minimal, if Dupont reports that "1/2 of patients had central nervous system side effects such as dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming." Persons on the Crix list have complained of inability to concentrate, inability to think, feelings of being in a drunken stupor/disorientation, nightmares etc. And they are reported as not being so minor. The 600 mg dose, which is the one approved, has the highest incidents of these side effects, as opposed to doses of 200 mg or 400 mg. Originally Dupont said the best way to avoid these CNS side effects was to take the 600 mg dose at night (threee pills once a day-200 mg). But I think Dupont recommends it twice a day to avoid other side effects, such as rash. Which means the CNS side effects will still be present. Remember how the press releases at Geneva raved about the tolerability. CNS side effects appearing in 50% of patients are not insignificant. The drop out rate was around 20%. Note they comment that it is priced less than the standard combination regimen which includes a protease inhibitor. AIDS organizations were circulating petitions to ask Dupont NOT to price Sustiva similar to protease inhibitors, but to price it the same as other drugs in the class. It looks like it is priced closer to PI's than to NNRTI's, although I'm not sure how other NNRTI's such as delavirdine or nevarapine are priced. Less, I suspect. Duponts says: "When used in triple-combination therapy, as it was in studies, Sustiva will be less expensive than the current standard of care including protease inhibitors, DuPont said." It should be, according to the petitions being circulated by HIV groups, physicians, some institutions. "DuPont Pharmaceuticals said the accelerated approval of Sustiva is based on analysis of plasma HIV-RNA levels and CD4 cell counts in controlled studies of up to 24 weeks in duration. At present, there are no results from controlled trials evaluating long-term suppression of HIV-RNA with Sustiva, the company said." In one Dupont study 005 that started with 137 patients, in 3 treatment arms, (about 37 patients each): at 24 weeks, there were about 21-23 patients remaining at 24 weeks, and only 11 patients remaining at 36 weeks i.e. only 30% of patients remained at 36 weeks. And this included patients who had changes made to their regimens at 16 weeks, if the viral loads were detectable. It will be interesting to see if the press release includes On Treatment analysis or Intent to Treat or Time to Viral Failure. I think that the FDA is now requiring data to be reported as Intent to Treat or Time to Viral Failure. Both methods are more stringent than On Treatment analysis, which only looks at patients remaining in the study, and makes the results look much better than they really are. Many have said all along, that although Sustiva and other NNRTI's are potent initially, the effect is not sustained. And in all the studies so far, the maximum effect was reached at 16 weeks or 24 weeks and then declined. And better results were obtained in all studies which included a combination of an NNRTIsuch as Sustiva or Nevaripine or Delavirdine, PLUS a protease inhibitor and one or two nukes. "Safety data from trials showed Sustiva is generally well tolerated. The most significant adverse events associated with Sustiva therapy are nervous system symptoms, including dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming. These symptoms were reported in about half the patients using the drug." Plus rash occurs in about 1/3 of patients, other side effects are nausea, vomiting, flu-like symptoms. Apparently the most disurbing side effects are the CNS symptoms.