Does the FLAME data put indacaterol/glycopyrrolate as a superior LABA/LAMA in the ex US scenario based on existing evidence to date?

Dr. Ferguson:   Okay, so first of all, we start with the disclaimers. This is personal opinion. I actually haven't read the complete FLAME data, which just came out in The New England Journal, none of the data is actually formally presented in abstract or other science format here, but it was part of a press release showing that there was an approximately 17% greater reduction in exacerbations in patients taking a LABA/LAMA in this particular case. The once-a-day product in Europe of indacaterol/glycopyrronium compared to the twice-a-day dry powder inhaler salmeterol/fluticasone. It had certain criteria which I think is important that we need to look at. One, it required everybody going into the study had to be an mMRC [modified Medical Research Council scale] of at least two, so they were definitely symptomatic. They had to have certain criteria for drugs that they were coming into the study on. They were only required to have one exacerbation out-patient, and not necessarily in-patient, to qualify for the study, so a risk group, but not a high, high-risk group, and then the outcome is as I described. There's a lot that we need to know, and this part is totally hear-say, because this is through somebody else who says some of the other analyses, that the benefit was exclusively in the patients who had one exacerbation, and if you had more than one exacerbation, there was no difference between the two. I don't honestly know about severe exacerbation. The net effect of it, from my standpoint, at this stage is it's good to have more information. This is helpful information. It's starting us down this pathway of trying to understand and separate out the role of ICS versus dual-bronchodilator therapy. It isn't the answer all. It's one study with one particular brand of medication, actually one that we don't have available in the United States. It's great information. Is it enough to make us change all of our guidelines and pathways and everything else we think about today? No. I clearly want to do and need to do more information gathering with it.

Dr. Mannino:   The epidemiologic perspective from me is that, as I said at the press conference, one good study is just that, one good study. It provides some additional evidence. I don't think at this point, it's going to change or should change practice, although it certainly might provide a level of comfort when we're having patients like the last one that we discussed where you're perhaps looking at stepping down or trying to figure out at what point there may be a benefit to go with a LABA/LAMA versus a triple. Again, I think we need additional data. A lot of times, in these type of studies, the devil is in the details, and you see a benefit in a select sub-group as opposed to the overall group. I just say stay tuned, and I would like to see additional studies that perhaps have these head-to-head comparisons. More are coming.

Dr. Ferguson:   They are coming, and that's the point. Because of the development of triple therapy, one of the key regulatory requirements is that you have to show that the triple therapies are better than double therapies, and the primary end points for all these are exacerbations. We do have ongoing studies that are in various stages—one almost completing, a couple that are ongoing—that are looking at LABA/LAMA versus LABA/ICS versus triple, and it's all in a comparative head-to- head same population. Between these couple of studies, in a couple of years, we will be able to actually answer this definitively. It's one more step, but we aren't there.