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

To: Peter Singleton who wrote (3736)	2/4/1998 7:37:00 PM
From: Oliver & Co	Respond to of 6136

Studies show AIDS "cocktails" help children too February 4, 1998 04:58 PM By Maggie Fox, Health and Science Correspondent CHICAGO, Feb 4 (Reuters) - Strong triple-drug "cocktails" that show near-miraculous results in many adults in controlling the AIDS virus, are working in children too, researchers said on Wednesday. Children are not normally given "cocktail" treatments, partly because of fears the toxic drugs will make them too ill, partly because of some evidence they would not react as adults do, but most of all because of a lack of studies to show what doses they should be given. The standard advice has been to give them Glaxo-Wellcome's AZT, or perhaps a combination of just two drugs in the same class. Proper use of AZT during pregnancy and just after birth has been shown to dramatically reduce mother-to-child transmission of the disease. But scientists reporting at a conference on AIDS this week say they are starting to test multiple drug regimes in children -- and they are working. Sandy Burchett of Harvard University and a team from across the country tested 432 seriously ill children with a cocktail including didanosine (Videx or ddI, made by Bristol-Myers Squibb BMY ), AZT, and nevirapine -- a member of a new class of drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs) -- marketed by Boehringer Ingelheim as Viracept. All the therapies killed off the virus at first, though levels crept back up. Nonetheless the effects were good. "Only five percent of the subjects who were enrolled died. That is many fewer than we would have expected," Burchett told the Fifth Conference on Retroviruses and Opportunistic Infections. Overall, 40 percent of the children responded to triple therapy, as opposed to 14 percent of those on just ddI and AZT and eight percent taking only ddI and nevirapine. "Not all triple therapies are created equal. This group of subjects were very advanced in their disease," Burchett said. The good news was the drugs did not make the children as sick as had been feared."The therapies were fairly well tolerated," she told the conference. There was fever, malaise and stomach upset or diarrhea in 12 to 13 percent of all the children. "This was the first time we had exposed a large number of children to nevirapine," she added. More of the children who got nevirapine in the combination, 20 percent as compared to three percent of those given ddI plus AZT, developed a rash. Her group would now test four-drug therapies, Burchett said. "We don't know that they don't respond in the same way (as adults)," she said. A group at the University of California at Los Angeles, working with La Jolla, California-based Agouron Pharmaceuticals AGPH , treated 60 infected infants and children with Agouron's nelfinavir, a new protease inhibitor. The children tolerated the nelfinavir and levels of virus dropped -- especially when a reverse transcriptase inhibitor such as AZT or ddI was added. In adults, adding protease inhibitors to the older class of drugs that includes AZT and ddI proved to be what it took to suppress the HIV virus enough so that people got well again. The hope is that similar mixtures will help children recover as well -- even if their more active immune systems do not respond in quite the same way. REUTERS c 1998 Reuters. All Reuters articles are delayed at least 15 minutes.

To: Peter Singleton who wrote (3736)	2/4/1998 7:39:00 PM
From: Oliver & Co	Read Replies (2) \| Respond to of 6136

The problem with Fortovase is too many pills, and many patients have already been exposed to SQV. My patients do not like it.

To: Peter Singleton who wrote (3736)	2/5/1998 3:42:00 PM
From: margie	Read Replies (2) \| Respond to of 6136

Viracept's market share increased to 37.7% in December, while Crixivan market share was 31. 6% in December, based on IMS Drug Distribution Data, which surveys monthly manufacturer sales to all channels. Also confirmed in Lehman report that Joe E. just posted. As far as your comments: <<Apparently, there's a lower rate on Roche sales of their own PI, a higher rate on Roche sales of Viracept, and they pay AGPH the greater of the two.>> I believe the arrangement is that Agouron gets royalties on whichever protease inhibitor sells more, and the larger the difference, the higher the royalties, an unusual arrangement, but it seems like that is more favorable for Agouron. L. Moss on AOL pointed out what the royalty arrangement was and IR confirmed it. Also Roche did not 'choose' to present data comparing Saquinavir to Crixivan, that is the way the European CHEESE study was designed originally, to compare the two protease inhibitors. Not too many companies would pass this opportunity to issue a press release to that effect, especially when the results showed such an increased rate of recovery of CD4 cells with Fortovase compared to Crixivan, at least in that study. As far as being worried about Fortovase being 'better,' look at the data at a new web site: natap.com which is still under construction. Check 'What's New' and look at the index for Fortovase. It all depends which particular study you look at. I am sure you noticed that Vertex chose to issue a press release which compared a very small study of different protease inhibitors in groups of only 5 or 6 patients, even though the abstracts at the retro meeting seemed to include data with more patients. Study NV 15355: Comparing New Fortovase to Old Saquinavir HGC 16 week analysis of 48 week data, Saq +2 nrti's Fortovase Saquinavir Baseline N 81 90 Baseline CD4 448 408 Baseline viral load, 63,000 63,000 CD4 increase 16 weeks +97 +115 HIV RNA <400 80% 43% HIV RNA <50 copies 46% 28% HIV RNA decrease <400 -2.0 log -1.6 log HIV RNA <50 copies -2.5 log -1.8 log SUN STUDY Fortovase+AZT/3TC This is an open-label, non-comparative examination of the triple regimen of saquinavir SGC (soft-gel capsule, Fortovase}, plus AZT and 3 TC. 42 treatment-naive individuals Mean baseline, HIV RNA 4.8 log 10, 63000 range Mean CD4 419 cells The study is ongoing and the following data is preliminary. The investigators reported that after 20 weeks: -the reduction in viral load was 3.34 log (range: -4.5 to 2.2 log). for 23 patients that could be evaluated. -91% were <400 copies/ml (undetectable) -60% <20 copies/ml. CD4 increase +259 from baseline of 419 cells -19/42 participants had withdrawn from the study by week 20 and were not included in the analysis. Two withdrew due to adverse events, 3 due to non-compliance, 4 due to refusal of treatment, 6 lost to follow-up, and one missed the week 16 visit. The most frequent side effects related to study drug (>5%): nausea, vomiting, diarrhea, and headaches. Lab abnormalities: One person had a grade III AST/ALT (liver function tests) at week 2 which resolved after discontinuing study treatment. One person had a grade IV AST/ALT at week 12 associated with acute hepatitis A. One person had a Grade III AST/Grade IV ALT at week 20 associated with acute hepatitis A. An approximate 20% incidence of diarrhea has been reported associated with saquinavir SGC in a different study. The European data that Agouron reported is more comparable to the data from the CHEESE study. Three 24-week studies were designed to assess BID regimens of VIRACEPT in combination with two nucleoside analogs. 46 patients Mean viral load - Baseline 4.9 log10 mean CD4+ cell count -Baseline 346 cells/mm3. Thirty-six patients received: 1250mg VIRACEPT + d4T + 3TC BID 1250 mg Viracept +AZT/3TC BID 10 patients received: 1000mg VIRACEPT+ AZT + 3TC. BID After 24 weeks of therapy: 93% (14/15) of patients who received the 1250mg VIRACEPT BID regimen and 10/10 at 1000mg VIRACEPT BID regimen had viral loads below the limit of detection (<400 copies/ml). Of these patients with HIV RNA below the standard assay limit of detection, 100% (12/12) of those receiving 1250mg BID and 70% (7/10) of those receiving 1000mg BID were also below the limit of detection of an ultrasensitive assay (<50 copies/mL). Upon completion of the 24-week study, patients who were on the 1000mg BID VIRACEPT regimen will be increased to 1250mg BID. The BID regimens were well tolerated. Further data from the SPICE study in Europe, in patients na‹ve to protease inhibitor and reverse transcriptase therapy: At 24 weeks: 100% of patients on Saquinavir and Nelfinavir plus two non-nucleoside reverse transcriptase were undetectable using the ultrasensitive assay <50 copies For experienced patients, 86% were undetectable <400 copies/ml, and 75% were undetectable <50 copies. This combination demonstrated very robust viral load suppression in pretreated and na‹ve patients. Both Viracept and Saquinavir are potent, and in combination, they appear more potent.