"Wolf" Brings Eyewitness Report on Boceprevir -- From Copenhagen

In the comment-box, tonight -- Wolf, a long-time friend to this blog -- has provided some expert on-site reporting, from Copenhagen -- and the 2009 EASL, thus:

. . . .Schering-Plough presented their SPRINT-1 data in Copenhagen today. This is their naive trial (not non-responders). A couple of initial observations although I am still digesting the data:

1. Discontinuation rates in the boceprevir arms ranged from 26%-50% vs the 10-15% we usually see with current standard of care ie.PEG+ribavirin. This observation was left unexplained however premature discontinuation in HCV trials is usually associated with some tolerance or compliance issue.

2. My greater concern is their numbers, as presented, do not add up. SP claimed a 75% SVR in their best treatment arm which included 103 patients ie. 77 patients had SVR. However they also report 27 patients discontinued. We are already at 104 patients not including the patients that did not respond (at least 8 patients, probably more from another slide, ie. n=112). What does this mean? In my mind it suggests that the 75% SVR being reported is not based upon an ITT (intent to treat analysis). Under ITT, patients that d/c should be counted as non-responders as they did not complete the protocol. It appears that SP may be counting some discontinuations as responders. The FDA typically will look at a strict ITT analysis when interpreting the data.

3. Their 38% response rate in Genotype 1 patients with PEG INTRON + Rebetol control arm is poor. If I were Roche, I would be capitalizing on this lacklustre reponse to gain greater market share for Pegasys + Copegus.

4. It is my opinion that TID (three times a day) dosing will be very challenging. The boceprevir pharmacokinetic profile suggests that the drug must be taken every 8hrs whereas the ribavirin component is taken every 12 hours. Standard rule: You do not mix bid and TID dosing. For example, if a patient takes their first dose of boceprevir and ribavirin at 8:00 AM (4 pills BP, 3pills riba), they must take their second dose of BP at 4:00 PM (4 pills), their second dose of riba at 8:00 PM (3 pills) and their 3rd dose of BP at 12:00 AM (4 pills). Repeat every day for the next 48 weeks! Add in once weekly interferon injections and you can imagine how difficult this will be from a patient pill burden and compliance point of view. Using HIV as a comparator, we suspect that upwards of 90% compliance will be required to avoid the emergence of drug resistance.

Significant advantage will go to the company that developes a BID (twice daily dosing). This would allow synchronization with the ribavirin dose and reduce the times in which drug is taken from 4 to 2 per day. Vertex has recognized this issue and have been doing these studies.

Advantage Vertex.

-- Wolf

Thanks, Wolf! -- this greatly enriches the dialogue, and my site (my squib on it, from stateside, today). Any chance you'll still be there for Vertex's "Late Breaker" session on Saturday? I'd love to have your take on that!