Replies to post #76542 on Biotech Values

[DewDiligence]

Re: Effect of ribavirin on the “front end” of HCV treatment

I think there’s some confusion in this thread because people are talking about two different things: i) the anti-replication effect of ribavirin per se; and ii) the incremental value of ribavirin in achieving RVR when it is combined with interferon.

I posted in #msg-36533555 that ribavirin as monotherapy has been found to produce a mean reduction in viral load of ~0.8 logs, which is not much. (This figure is based on comments from the CC’s of various HCV companies during the past few years.)

However, ribavirin’s low efficacy as a monotherapy does not imply that it has little incremental value in achieving RVR in combination with interferon; to the contrary, no less an authority than Josh Boger thinks that this is ribavirin’s main contribution in HCV therapy!

How can the two paragraphs above be reconciled — i.e. how can a drug with such weak anti-replication efficacy produce a substantial increase in RVR when added to interferon? This is the question to which no one knows the answer (yet).

[dewophile]

when i say lambda appears more potent i am purely stating that based on VL reduction - no commentary as to MOA

PS: i just got around to looking at the posters. they have a second poster modeling kinetics based on data from weekly dosing cohorts through week 4 to predict cEVR (a 12 week endpoint). per the model (which admittedly may be off given it"s based on only 22 patient data) .66ug lamda should yeild comparable efficacy to 1.5 of alpha

[iwfal]

Given that RVR is a good indication of SVR and that Rib significantly increases SVR, I would think adding Rib to interferon also increases RVR. If thats the case, then you would think Rib should play a role in early viral kinetics. However, I can't find data to support that hypothesis.

Just to close out this thread there are at least two separate papers indicating that this is, in fact, not true. Rib does not add to early response when combined with ifn-a - it kicks in later in preventing breakthrough and preventing relapse.

See ivillage site for details.

Note that this is interesting given that the logic you extoll above is reasonable - perhaps it is because rvr has a smaller false negative than false positive? (I do not actually know this is true - but suspect it)