allotment, page-104

Worthind,

Your comparison is misleading. You have compared the Biotron phase I trial using 200 mg of drug in monotherapy (designed as polydrug component) over 7 days to Telaprevir over 14 days (with 50% rebound). Comparing like with like is only possible for the phase II trials (each at 28 days). A better comparison would use the most relevant phase IIa data (400 mg BIT225 combo caused a 4.0-log reduction over this period).

RCG,

"my constant references to insignificance are my trying to get the concept of statistical significance across to a few who don't seem to understand it"

Here we go. The data was statistically significant. What do you make of an average 90% in reduction in viral load over SOC with a natural probability of about 0.00000005? You don't seem to understand that you can't simply write off the significance because it suits you.

"But the Pharmasset trial presented at AASLD in Nov showed that in geno 2 and 3 at lease, a polymerase inhibitor in combination with ribavirin (which has a modest effect on viral load) could produce both RVR and SVR, and resistance did not develop. Hence the polymerase inhibitor is extraordinarily potent (at least 1000x more than BIT225) and has a high barrier to resistance."

This is incorrect. You are not referring to HCV-1, you are comparing to HCV-2 and HCV-3, against which BIT225 is untested. Additionally, HCV-2 and HCV-3 are easier to treat, allowing you to utilise wildly exaggerated figures (for which you have still not provided your calculations). Further, you underplay the importance of the ribavirin component - shown to increase reduction by 1.5-log.

In your rush to skew the data, you now also appear to be defeating your own argument. You claim:

"Remember that telaprevir ALONE is $50,000 for a course. Therefore, my guess is that the companies wanting to remain players in the HCV market will go for polymerase and protease inhibitors first."

It is for this very reason that these p. inhibitors will be priced out of a number of critical markets. For the substantial number left with the SOC, the addition of BIT225 could have significant impact on efficacy, dosing period and cost of any polydrug treatment. The cost of treatment can be impacted by the reduced dosing regimen. It is a multi-billion dollar market so it is hard to discount the potential of increased efficacy at similar or reduced cost. Development costs represent a small fraction of the potential revenue.

"With respect to side effects, it was the active drug group patients that seemed to have the problem, suggesting that it was not the SOC, which typically does not cause a lot of GI upset."

GI effects are common side effects, as I'm sure you're aware. In PEG IFN RIB (SOC) clinical trials, it is estimated that between 10% - 15% of patients drop out due to adverse effects (a much lower figure than in clinical practice). This is exactly in line with the ph IIa results. The off-target effects of the SOC are well documented, you will have trouble twisting them.

Your clever use of massaged data and skewed comparisons is starting to scrape the bottom of your barrel of reasons why BIT225 cannot enter a $20 billion market.