So the results of the Aspen trial raise this very important question of, in clinical practice, what dose are we going to use. Uh, regulatory authorities in the United States, so the FDA have approved both the 25 mg dose and the 10 mg dose. Um, in, in Europe, CHMP, uh, have recommended the approval only of the 25 mg dose, and so it's likely. Uh, relatively soon, the 25 mg dose only will be approved in Europe. So, so why the difference and what should we be doing clinically in terms of dosing of benzacateib? I'll give you my personal opinion. Uh, the exacerbation efficacy data is similar, it's 20% for both doses. The additional benefit of the 25 mg dose is on preventing lung function decline, which I think is clinically very important, and also an advantage in terms of symptoms, and there's a debate about how large is that difference between the groups and is that clinically relevant for all patients. Uh, my view is, it's clinically relevant for many patients, and there is a, a better symptom improvement with the 25. For all of those reasons, my preference will be to prescribe the 25 mg dose to my patients, because I think the balance of benefit, uh, is there in favor of the 25, and the small increase in. The risk of hyperkeratosis that we see with the 25, um, is small, uh, and didn't result in discontinuation or significant problems for patients, and so I don't think it offsets the, the risk, and I think that reasoning is, is why the CHMP, why the European regulatory authorities have decided to go with a single dose. Uh, I struggle to think of any patient where I would want to start the 10 mg. I think the only scenario I can see where I would be looking to prescribe a 10 mg, if it was available, would be the very rare occasion where you've got a patient with persistent hyperkeratosis who needs the drug, but you want to drop the dose to reduce the risk of that side effect. I think that's really unlikely to, to happen, but I, that's the only scenario I can think of where I'd be looking to use the 10 mg. Um, so that, that's my personal opinion, but it's very much based on the extensive data from Willow and Aspen, uh, and a, a deep dive into the safety data in particular.
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