PARP (poly ADP-ribose polymerase) inhibitors have had a rough time of it in the clinic. Sanofi had one (iniparib) fail, but it later turned out, embarrassingly, that it wasn’t really a PARP inhibitor at all (update: more on this here). AstraZeneca had a legitimate one fail as well (olaparib). Merck got out of the area and outlicensed their compound to a small company called Tesaro, and Pfizer spun their molecule off to another small outfit, Clovis (who have since had a wild ride of their own with other compounds). Meanwhile, Medivation recently acquired Biomarin’s PARP inhibitor, talazoparib.
So it’s been pretty messy, but the potential of PARP inhibitors has remained in the “unproven” category. Until today, that is. Tesaro announced that neraparib, the ex-Merck compound, showed very solid results in progression-free survival in three different genetic varieties of ovarian cancer in a 500-patient trial. This has their stock up over 100% as I write, and the other folks developing PARP compounds aren’t doing badly, either. We don’t measure stock in the mood of patients who are actually being diagnosed with ovarian cancer, but I would guess that if we could, that index would also be up, and good for them, because they need all that they can get.
Interestingly, the AstraZeneca compound, olaparib, has been approved in ovarian cancer, but only for patients with the BRCA mutation (its clinical performance was not enough in other patients, to the point that going back and looking at the BRCA subgroup was something of a rescue operation). Neraparib worked very well indeed in the BRCA patients, but showed significance in others as well. It’s not clear to me why these two should be this different, and this illustrates (once again) the value of so-called “me-too” compounds. Now, all these things have been under development more or less simultaneously, so it’s hard to call any of them a “me-too”, but to an outside critic of drug development, they certainly would be. So many companies in the same space! So wasteful!
It’s not a waste, and today’s results show why. It’ll be quite interesting to see the clinical results of the other PARP compounds in this light. You’d expect more differences to become apparent as they are tried in combination with other agents, too. This story is being written as we watch.