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

To: Casaubon who wrote (342)	11/8/1999 9:48:00 PM
From: scaram(o)uche	Read Replies (3) \| Respond to of 1169

I said that it was a well-written release, not proof of concept. Your highlighting is supporting my point. So far, I do not consider the data proof of concept. It's a miserable failure of POC. We already knew, from the quarterly conference call, that such was a given (alluded to in a couple of Miljenko's posts?). Didn't expect the wording to be so strong in that regard, however. I'm not sure it's "a good thing" to reduce the ALT levels without a concommitant reduction in viral load. I'd lean toward betting that it is. However, as you know, one can't take that out of the context of toxicities (including immunosuppression) and competitive projects. Perhaps there will be statistical significance in reducing viral load in combination with interferon. Looks like we're going to find out. It would be great if the world of pharmaceuticals could be perfect. It isn't, but many scientist-investors feel that a specific cure for every ailment is just around the corner. The mechanism of synergy between IFN and ribovirin has not, to my knowledge, been described. I'm looking forward to helicase and protease inhibitors, but, for the mean time and if said synergistic activity is a reflection of IMPDH inhibition, I feel that there's reason to proceed with the testing of 497. I might give it away if I were JB, however...... tiny or no upfront, rigid performance standards, and good royalties. Could be a big product. Can you tell me that it won't be? Does anyone know if any companies other than SGP are working on PEGylated IFN? Roche??

To: Casaubon who wrote (342)	11/9/1999 1:11:00 PM
From: Biomaven	Read Replies (1) \| Respond to of 1169

So far, I do not consider the data proof of concept. Perhaps there will be statistical significance in reducing viral load in combination with interferon. I'm not sure it's "a good thing" to reduce the ALT levels without a concommitant reduction in viral load. Well ribavirin doesn't markedly reduce viral load as a monotherapy either: J Hepatol 1998 Jul;29(1):29-35 Related Articles Effect of ribavirin on virus load and quasispecies distribution in patients infected with hepatitis C virus. Lee JH, von Wagner M, Roth WK, Teuber G, Sarrazin C, Zeuzem S Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe-Universitat, Frankfurt a.M., Germany. BACKGROUND/AIMS: The combination of ribavirin and interferon alfa has potent synergistic effects in the treatment of chronic hepatitis C. The antiviral mechanism of ribavirin is unknown. We investigated whether a transient initial antiviral effect of ribavirin was sufficient to improve the response to interferon. METHODS: Fifteen HCV-infected patients (ten male, five female; mean age 45.4+/-11.0 years) treated with ribavirin (1000-1200 mg) and 17 untreated patients with chronic hepatitis C (11 male, six female; mean age 45.6+/-9.9 years) were investigated. All patients were either non-responders to (n=19) or relapsed after (n=13) previous interferon treatment. Serum HCV-RNA concentrations and HCV quasispecies distribution were serially measured over 4 weeks by quantitative reverse transcription-polymerase chain reaction and single-strand conformation polymorphism analysis, respectively. RESULTS: In six of the 15 patients treated with ribavirin, but in none of the controls, serum alanine aminotransferase levels declined by at least 30%. Pretreatment HCV-RNA levels ranged from 5.0x10(5)-5.0x10(7) copies/ml. After initiation of ribavirin treatment, minor (0.5-1.0 log) or no changes (<0.5 log) in total hepatitis C viremia were observed in ten and five patients, respectively. In HCV-infected patients without treatment 7/17 patients had minor and 10/17 no changes in viremia. Polymerase chain reaction amplification of the hypervariable region-1 of HCV was successful in 13/15 treated and in 17/17 untreated patients. Changes in HCV quasispecies according to the single-strand conformation polymorphism band pattern occurred in only one patient treated with ribavirin and in three of the untreated patients. CONCLUSIONS: Ribavirin monotherapy has no initial antiviral effect on total hepatitis C viremia nor on HCV quasispecies. Unlike the rapid emergence of antiviral drug-resistant strains in HIV-infected patients, no viral escape phenomena are observed in HCV-infected patients treated with ribavirin. Seems to me (as Miljenko said) that VX-497 looks like a potentially better version of ribavirin. Peter