Idenix Pharmaceuticals (IDIX)

[DewDiligence]

If those AASLD guidelines are still in place after the two-year Tyzeka data released last fall, then NVS and IDIX better get to work changing them because they are clearly out of date.

I’ve posted at length about the randomized head-to-head data showing Tyzeka superiority to Hepsera (#msg-21365649), which is the leading HBV drug in terms of sales.

The two-year resistance profile of Tyzeka in patients where the drug works is excellent—see #msg-14377860:

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“For telbivudine-treated patients who achieved PCR negativity at week 24, the per-protocol rates of resistance at two years were 4 percent in HBeAg-positive patients and 2 percent in HBeAg-negative patients. Per GLOBE study protocol, resistance was defined as HBV DNA return to >5 log, or to within 1 log of baseline.”
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The higher resistance figures in the references you cited are ITT figures, which are irrelevant for the reason mentioned in #msg-14403420: the resistance that occurs is almost entirely within the subgroup of patients where Tyzeka never works in the first place. (These patients will of course be switched to another drug.) There is no preclinical or clinical evidence I’m aware of that a short regimen of Tyzeka induces resistance to Baraclude or Hepsera.

Regarding HBV/HIV co-infected patients, this is a clear differentiating factor for Tyzeka because it has zero efficacy against HIV in animal models and thus it can’t cause premature resistance to HAART cocktails as Lamivudine, Baraclude, Hepsera, and Viread can. (The interferon drugs have this benefit too, but they are rarely used in HBV due to their poor therapeutic index.)

Lamivudine and Viread are approved drugs for HIV, Hepsera is a close chemical cousin of Viread, and Baraclude recently received a warning for its activity against HIV (#msg-17360663). With a modicum of marketing, Tyzeka should clearly become the HBV drug of choice in HBV/HIV co-infected patients.

I suspect the AASLD guidelines tend to lag behind the state of the art and this is one reason Baraclude took so long to ramp up despite being clearly the best approved HBV drug during 2005 and 2006.