Clinical Advances and Challenges With Biosimilars - Episode 13
Bruce A. Feinberg, DO: If you’re bringing a product to market, and you don’t have to do clinical trials in 6 different indications, shouldn’t that price differential be a lot greater than 10% or 20%? And, is that hurdle very different when you’re dealing with life-threatening disease with a survival that could be measured in months or a few years?
Hope S. Rugo, MD: It’s a complex situation. I’m going to deal with the first question, second. First is, how do we think about extrapolation in cancer? We did our trial with the trastuzumab biosimilar from Mylan in the first-line metastatic setting. In others, including the other published trial with the trastuzumab biosimilar from Celltrion, I chose the neoadjuvant setting with a different chemotherapy regimen than we commonly use. Both studies show similarity. There isn’t a big difference in that area. If you do the trials in the neoadjuvant setting, you can’t control what treatment people get after surgery, and it may differ from whatever chemotherapy somebody else would give in the neoadjuvant setting. So, you’re always going to have issues with comparisons. In the biosimilar world, most of the people who get first-line metastatic treatment will not have previously seen trastuzumab, so it’s not really an issue. I think that both studies have validity.
Would you then choose one in one setting and another in another setting? No. I think that you’re going to use the biosimilar product across the different indications. With trastuzumab, and I think with these antibodies, we’re fortunate in that the drug—drug interactions are quite minimal. You’re not really worried about seeing any. For example, if you use trastuzumab with vinorelbine, instead of paclitaxel or instead of docetaxel, are you going to see a different interaction? We already know that’s not the case. A lot of studies have been used. We sort of give it with whatever, with impunity, and we have only seen interactions when it’s the other drug that’s interacting—like lapatinib, where you give a lower dose.
I don’t think that that’s going to be an issue. We also know that you can be exposed to the drug with different combinations, over a long time, without changing the toxicity profile. So, from an efficacy standpoint and a safety standpoint, we’ve already tested the originator product with a lot of combinations and have not seen a difference. I don’t think we need to do that. I think that people, in general, will be fairly comfortable with extrapolation. I think one thing that people have brought up in these conversations is, in the metastatic setting, you’re not doing it with the idea of cure, even though some people will have very long-term disease control. We know that to be the case. So, do you need to show survival impact?
And I think that, again, because you can show a correlation between response, progression-free survival, or disease-free survival, and overall survival depending on the setting—trastuzumab has been studied more than, really, any other drug in breast oncology—I think that we can feel very secure about that. I wouldn’t worry. We’ve also even seen recent data, from a study presented at the ASCO Annual Meeting, demonstrating that you could give 9 weeks of trastuzumab and, where it wasn’t equivalent—it didn’t meet the equivalency to a year of trastuzumab—it was still pretty good. And so, in countries where you can’t pay for very much, you could still give some, and it would be better than giving none.
How does that impact cost? Should you say, “You actually didn’t have to do all these clinical trials so, therefore, you should make your product even cheaper?” Well, again, there’s a huge amount of work to do. People show presentations about how to develop a biosimilar—these triangles. And the triangle is upside down for the originator product, where your clinical part is really big. But, it’s the opposite way around for the biosimilar, where you had to do all these studies and show similarity. You had to do a lot of different trials, and you’re coming up with a different agent where there’s a lot of competition. So, you actually have to think about that. You have to think about the amount of money and work that goes into getting to that place, where you get approval and it goes onto market, and also the competition, which, of course, the originator product doesn’t have. What does that mean for cost? It is my hope and, I think, many others’ that the competition will drive down costs—not just of the biosimilar, but the originator product as well. And, we’ll end up with a much bigger cost differential, over time.