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

To: Steve Fancy who wrote (4714)	7/2/1998 11:57:00 PM
From: Peter Singleton	Read Replies (4) \| Respond to of 6136

Folks, hate to be the bearer of bad news, but here's a post from the Motley Fool AGPH thread. Testact is a frequent poster, and seems knowledgeable. I'm passing this on without judgment either way in the interests of full discussion on the company. Btw, I don't think he liked Peter Johnson's tie, either ... : ) Peter Subject: Re: Relative importance of NRTIs Date: Thu, Jul 2, 1998 10:04 PM From: Testact Message-id: <1998070222041700.SAA11819@ladder03.news.aol.com> I am back from Geneva and have the following response to your post and highlights from the meeting: NRTIs will remain the cornerstone of ARV in the future!!! I have no idea where your comment that their importance was diminished comes from. All patients on HAART receive two nucleoside analogs and the standar of care is 2 nukes and a PI....for now....sustiva will change that NNRTIs (actually let's just say Sustiva) will gain rapid acceptance in the treatment naive setting until the toxicities (lipodystrophy, diabetes, etc) are better understood. This was based on my conversations with at least 10 docs (many opinion leaders)! PIs will still play a major role in salvage (which is where most of the treated patients are) but Sustiva will have an impact on Viracept sales. I spoke with Peter Johnson at the meeting regarding the Shinogi compound; he obviously is excited about the prospect of it being active in Sustiva resistant strains. However this in in-vitro data and I am aware of better pre-clinical compounds than this one. The pharmakokinetics of this compound and dosing uncertianty (probably BID) make this a real question mark. Remune: spoke with A. Fauci and others....this compound is a dog and will see minimal uptake in the marketplace. Japan Energy PIs - to early to tell.....I was told by a few people at the meeting that these did not look as good as the Parke-Davis, PNU and BMS PIs in development. I have to say I am puzzled on some of the deals Agouron is doing and I think the analysts are as well......this is obviously reflected in their stock price. Keep in mind all of these product acquisistions mean more R&D......and less bottom line for a number of years. Don't count on Remune to add much in the short-term. My prediction is that if Agouron's stock falls another 10% someone will snatch them up for their salesforce, Viracept and somewhat questionable pipeline, but at $750MM versus $1.2Bn they become a better target. Testact

To: Steve Fancy who wrote (4714)	7/3/1998 2:53:00 AM
From: Peter Singleton	Read Replies (1) \| Respond to of 6136

Folks, more worthwhile stuff from healthcg's reporting from Geneva. This time on Viracept BID. When the rubble and debris are cleared away from the wreckage of Geneva, AGPH will still be plugging away, selling their product, building their business ... Key quotes: the walkaway quote: "As compliance with combination antiretroviral therapy regimens is a major determinant of long-term success, subsequent nelfinavir-containing regimens should be based on BID dosing of this agent. " based on: "BID and TID nelfinavir regimens provide equally potent suppression of plasma HIV RNA with approximately 80% of patients achieving viral loads of less 400 copies/mL. Of those patients who responded, approximately 90% remain "undetectable" after up to 48 weeks of nelfinavir therapy. Pharmacokinetic analyses support the concept of a BID dosing regimen. No increased adverse events seem to be associated with the BID dosing schedule." healthcg.com /* section on Viracept BID Five Big Blue Ones Twice a Day Just as Good as Three Thrice Daily Forty-eight week results comparing BID and TID dosing of nelfinavir (in combination with 3TC+d4T) were presented from the European Nelfinavir Clinical Trial Group here today [1]. Patients included in this trial had to have less than 6 months of any previous antiretroviral therapy, be naive to either 3TC or d4T (later amended to be mandatorily naive to 3TC) and have less than two weeks of prior protease inhibitor therapy. The rationale for the study was based upon nelfinavir's well-known 3.5-5.0 hour half life which theoretically should allow for BID dosing. This study evaluated both pharmacokinetic (q8 hours vs. q12 hour steady state dosing) and clinical antiretroviral activity of the approved 750 mg TID and a 1250 mg BID dosing schedule. (The original study design included a 750 and a 1000 mg BID dosing schedule but was amended in 11/97 and all study participants in those 2 dosing arms were collapsed into the 1250 mg BID dosing group.) Preliminary results from 288 patients included in this analysis with up to 48 weeks of follow-up showed mean change in HIV RNA from baseline of 2.2 log for the BID group vs. 2.4 log for the TID group. Eighty percent of the patients in each group achieved plasma HIV viral loads below 400 copies/mL and approximately 60% in each group achieved plasma HIV viral loads less than 50 copies/mL. CD4+ T cell count changes at week 48 were +189 cells/mm3 and +166 cells/mm3 for the BID and TID groups, respectively. The most serious adverse events were reported: 4 patients discontinued from the BID group due to adverse events: 2 due to rash and 2 due to diarrhea. Overall, 9 (11.8%) of the TID patients and 27 (12.7%) of the BID patients reported moderate to severe diarrhea. No adverse events resulted in discontinuation of therapy in the TID group. Two patients in each group were discontinued from the study due to treatment failure - defined as two consecutive plasma HIV RNA measurements above 10,000 copies/L in previous responders. Adherance was reported to be good, with only two patients in each group discontinuing treatment for non-adherence reasons. One patient in the BID group was reported to develop hyperglycemia judged possibly related to nelfinavir after 12 weeks of study therapy. Plasma pharmacokinetics demonstrated median steady-state AUC for the 1250 mg BID regimen to be 51 mgxh/L vs. 45 mgxh/L for the 750 mg TID group. The Cmin for both groups was approximately 0.5 micrograms/mL. The authors concluded that the BID and TID nelfinavir regimens provide equally potent suppression of plasma HIV RNA with approximately 80% of patients achieving viral loads of less 400 copies/mL. Of those patients who responded, approximately 90% remain "undetectable" after up to 48 weeks of nelfinavir therapy. Pharmacokinetic analyses support the concept of a BID dosing regimen. No increased adverse events seem to be associated with the BID dosing schedule. These data provide immediately clinically useful information for simplifying nelfinavir containing regimens, allowing patients to switch or to be begun on 1250 mg BID dosing regimens. It is anticipated that this change in regimen will enhance compliance in that it will coincide with the dosing of the most commonly used RTIs such as AZT, 3TC, d4T and nevirapine. The lack of difference in adverse events between the TID and BID regimens also recommends this change in dosing as well. As compliance with combination antiretroviral therapy regimens is a major determinant of long-term success, subsequent nelfinavir-containing regimens should be based on BID dosing of this agent.