<<I'm not trying to diminish the achievement of VX-497, just discussing the implications of the data.>>
It is always good to have contrarian and/or one who ask questions.
As Peter pointed on Ribavirin effects and results on VL in HCV trials, somehow do not have pronounced effects, but in combination with INF do increase pts clinical response even for ones who didn't responded to INF alone and reduce VL (but by unknown mechanisms).
VRTX rationale is that potent IMDPH inhibitor like 497 will have similar results. So, they first want to check and confirm sustain ALT level reduction and stabilization (posible impact on VL) over longer period before moving forward with combination trial.
So far only INF show reduction in VL, and Rick note on new drugs targeting protease/helicase enzyme is next step. This approach is so hot that anyone from pharma or bts won't talk about. Still, it is far from clinical trials. It means that for now current therapy is best shot and one who can improve drug safety profile will be winner.
Miljenko
PS: Here are warning paragraph for Ribavirin/Intron and rationale to develop drug with improved safety profile.
WARNINGS AND CONTRAINDICATIONS
Hemolytic anemia associated with the use of REBETOL in combination with interferon alfa-2b (REBETRON Combination Therapy) may exacerbate symptoms of coronary disease or deteriorate cardiac function. It is advised that complete blood counts (CBC) be obtained at baseline and at week 2 and week 4 of therapy or more frequently if clinically indicated. The most common adverse experiences associated with combination REBETOL/interferon alfa-2b (INTRON A) therapy are ''flu-like'' symptoms, such as headache, fatigue, myalgia and fever, which appear to decrease in severity as treatment continues. Severe psychiatric adverse events may manifest in patients receiving therapy with interferons, including INTRON A therapy. DEPRESSION AND SUICIDAL BEHAVIOR, INCLUDING SUICIDAL IDEATION, SUICIDAL ATTEMPTS AND COMPLETED SUICIDES, MAY OCCUR.
Combination REBETOL/INTRON A therapy must not be used by women, or male partners of women, who are or may become pregnant during therapy and the six months after stopping therapy. Combination
REBETOL/INTRON A therapy should not be initiated until a report of a negative pregnancy has been obtained immediately prior to initiation of therapy. Women of childbearing potential and men must use effective contraception (two reliable forms) during treatment and during the 6-month post-treatment follow-up period. Significant teratogenic and/or embriocidal effects have been demonstrated for ribavirin in all animal species in which adequate studies have been conducted. These effects occurred at doses as low as one-twentieth of the recommended human dose of REBETOL. If pregnancy occurs in a patient or partner of a patient during treatment or during the 6 months after treatment stops, physicians are encouraged to report such cases by calling (800) 727-7064. |
