The Impact of Lynparza as a Cancer Treatment

PE: Can you update current research efforts into new indications for LYNPARZA® (olaparib)?

Doti: LYNPARZA, as you know, is a PARP inhibitor, right? Now, like every other drug, not only in oncology, in everything, it has a desired effect and adverse events. Most of these adverse events sometimes in oncology come from, they’re called the “off target innovation”. So, you’re planning to block one target in one specific cell, but you also block that target in another cell that’s not intended, or you block more than one target. So, the next generation of PARP inhibition is selective PARP inhibition, and we’re already developing a next generation of PARP inhibitors. One of the first molecules that will come to market is saruparib, which is a PARP1 select. So, selecting just PARP1, into this inhibition by bringing the benefits that we get from LYNPARZA, but with less adverse events in the indications that we are currently operating, but potentially to become a safer drug to be used in combinations in other places where PARP inhibitions may play a role. Not only in solid tumors but in other areas as well. So, I think that LYNPARZA set up the tone on how researching this area should be delivered, and then saruparib will actually expand into PARP inhibitions into other areas as well. And potentially also combinations because. one of the problems when you have specific adverse events is it makes some of these drugs hard to combine. By being more selective, you can expand the number of combinations that you can bring to market.

PE: Out of all of its approved indications, for which cancer type do you think LYNPARZA has had the greatest impact?

Doti: This is like asking somebody which kid they love the most. So, it’s hard to say. I think that there's two ways of measuring this. If you measure by number of patients impacted, it's easy to say probably breast cancer or ovarian cancer, because this is where you have the broad indications. But you have a patient with pancreatic cancer that has no other resource, and you are identified by this BRCA mutation. For that single individual, what LYNPARZA can bring is unique. So, it’s hard to say the impact from a society perspective. You may have one answer and from a patient perspective, you may have another. I think the most relevant part of this is, whenever there's a potential that by using a PARP inhibitor, we can make a difference. We will definitely want to go there. It all started with ovarian cancer, and we have a long line of usage there, but we've seen also in breast cancer that early adoption. And I’ll give you an example, not only the early adoption for the drug itself, but I think what LYNPARZA changed completely is the early adoption of testing for BRCA. So, 10 years ago, only a handful of patients were tested for that. Now today, a lot of patients, most of them when they reach in their journey in breast cancer or ovarian cancer, they are being tested by BRCA, and if you find that patient who has that BRCA mutation, that unlocks testing in the family types. So, in breast and in lung, we’re saving lives, not only by using the LYNPARZA in that case that was identified, but by preventing ovarian and breast cancer in the family members that have that mutation and they don’t know. And wouldn’t know if it wasn’t by that individual in the family that has ovarian or breast cancer.