When we last looked in on the long-running saga of PARP inhibitors around here, Tesaro had posted excellent clinical results for their compound and re-invigorated the whole field. At the time, I wrote “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.” We now have some more data that bear on both those statements.
AstraZeneca has reported more data on their own compound (Lynparza, olaparib) in ovarian cancer (where Tesaro’s compound niraparib, which used to be Merck’s compound, had performed so well). And the AZ compound delayed progression of ovarian cancer for two years compared to placebo. As that first link in the paragraph (from Adam Feuerstein) mentions, though, this is very similar data to the Tesaro trial, and the two trials were different enough that the two compounds may be functionally identical. So we now know that other PARP compounds can be equally effective, but there may not be such big differences, in the end. If such emerge, it might well be in combination regimens or in side effect profiles. The biggest problem with hitting PARP seems to be anemia, so that will be worth watching to see if one of the entries can differentiate itself out in clinical practice.
I had mentioned Clovis and their PARP inhibitor (Rubraca, rucaparib), which used to be Pfizer’s compound, and Clovis got approval for that just at the end of last year – again, for ovarian cancer. Feuerstein makes the point that this news is probably best for them, since they’re the smallest company with an approved drug, and it looks like they can probably ride on the results of these larger trials, in the anticipation that their compound is just as good as anyone else’s. Tesaro is hoping to get approval soon for niraparib, and Pfizer has an entry, too, ironically. After ditching their own compound to Clovis, they found themselves with another PARP inhibitor (talazoparib) when they bought Medivation (for other reasons), just in time for these compounds to become valuable again. It’ll be a crowded market, but women with BRCA-mutated ovarian cancer are going to benefit a great deal.
As an aside, it’s worth following those links above to the individual compounds to have a look at their structures. They are some of the most “med-chem” compounds you could ever want to see, at least to my eyes. And while they all have similarities, they all have somewhat different features as well. That just shows you how many ways there are to skin the cats in this business, since all of these compounds look to eventually make it through into the market.