Biotech Values

[DewDiligence]

Re: Precedence list of HCV drug-class combinations

Going from strongest to weakest synergy is as follows [according to IDIX]:

a) PI + NS5A inhibitor + purine nuke
b) PI + non-nuke + purine nuke
c) PI + pyrimidine nuke + purine nuke
d) PI + NS5A
e) PI + non-nuke
f) PI + pyrimidine nuke

Are purine nukes ipso facto better than pyrimidine nukes as an addend to protease inhibitors? Or do the HCV purine nukes in development (e.g. IDX184) simply happen to be better than the pyrimidine nukes in development (e.g. RG7128)? If we had some medicinal chemists here, we could get a good debate going on this question.

My initial reaction to the precedence list above is that IDIX is guilty of “talking book.” I.e., it’s not clear to me that purine nukes are ipso facto more synergistic with PI’s than pyrimidine nukes are.

The other salient point regarding IDIX’s precedence list is how low the non-nuke class has slipped. On this point, IDIX is not simply talking book insofar as IDIX does have a non-nuke in the clinic (IDX375); rather, I think it’s fair to say that non-nukes, with the notable exception of VRTX’s VX-222, have to date been the least impressive of the main HCV drug classes.