So from that perspective, I think we’re pretty well insulated. That is true. We saw 2 or more exacerbations in the last 12 months, whether it was during the COVID lockdown or outside of the COVID lockdown where the rates were going up or down, we know our patients are exacerbating patients, and that’s what we need in order to demonstrate the impact of the drug.
Sara Bonstein: I would just add the baseline characteristics that we put out from WILLOW and ASPEN, just the consistency on those on exacerbations, number of exacerbations, history of COPD asthma, that also just gives us comfort on very similar patients and the strength of the WILLOW data. We all are very aware of and looking forward to turning over the ASPEN data card Q2 of next year.
Joseph Schwartz: And then given you’ve been on the market in Japan with ARIKAYCE for a little while now, I was wondering if you can give us any insight into how the performance has been and how your trajectory looks relative to the U.S. at a similar point in the launch — in terms of things like sales rep productivity and penetration of physician practices or anything else you think might be important?
William Lewis: Yes. So I’m bullish on Japan. And the reasons for that are several fold. #1, I think the team out there has done a really good job in a very difficult environment. It’s hard for us to remember because we basically largely forgotten about the COVID era, I think, for a whole number of reasons. But it was only lifted in Japan in sort of the May, June timeframe of this year. Those restrictions were full on until that moment in time. And so they were working through that in the middle of a respiratory drug launch, which is hard to imagine. The other thing I would remind is that there were a number of surges of COVID where hospitals got filled up, and those were far more frequent and severe at the end in the last 12 to 18 months than they were in the U.S. and that made it even more challenging.
So the lifting of those restrictions is one driver that affords us the opportunity. But the more important one, in my opinion, is the new leadership we have in our Japanese territory. We brought on several key senior people in — at the beginning of this year, and they have really transformed the culture and the capability set of that team and their performance has matched that. And the reason we did that was because we knew not only do we have the refractory market to go and pursue, but we also have to get ready for bronchiectasis and what we expect will be frontline NTM so all NTM patients, and this is the team that can do it, and they’ve demonstrated that. So there are more patients, there are more hospitals, there are more relationships, and those are growing by the day.
Operator: Your next question comes from the line of Liisa Bayko with Evercore ISI.
Liisa Bayko: Congratulations on the data. First, can you give us a sense of when we can expect the next update from — I know you’re going to obviously amend the protocol and we get a peek at that data or more patients through the study for TPIP?
William Lewis: Yes. So I know that what I can tell you with confidence today is that we believe that we will have PH-ILD data in the first half of next year, the results of the study, and that’s probably the one anchor point I can give you. Will we update with additional PAH data? I suppose we can give that some consideration. I don’t see why we wouldn’t want to continue to at least give people the perspective that we’re seeing the same thing or what the trends are. This is an incredibly exciting dataset that we’ve seen grow and be consistent each time we’ve cut the data. So I don’t have a reason to expect it to change dramatically, but it could, and it’s important to highlight that. But so far, it looks good, it looks consistent and so I would expect to continue to be able to share that message. But as far as anchor points in time, I would look for PH-ILD trial results in the first half of next year.
Liisa Bayko: And will you make the same protocol amendment to that study as well?
William Lewis: No. It’s — the PAH study is the one that we’re doing the protocol amendment to for the open-label extension.
Liisa Bayko: Yes. Yes. The higher doses for PAH. And then just a question on ARISE. So I know in the placebo arm, you were at a 60% response rate and a much higher response rate on ARIKAYCE. As you look out to 12 months, how are you thinking of that placebo rate evolving if we look at kind of some papers out there, it looks like that could push into the 80% range just on — based on where it is today. And I know that’s some papers by Griffin, et cetera, but I just wondered how you’re thinking about that — I think you actually had like more like a 54% rate, but how that would evolve over the course of the second set of 6 months over the — to 12 months?
William Lewis: Yes. So I don’t — we don’t believe there’s much risk of the control arm sort of closing the gap with ARIKAYCE in any kind of significant way over the 12-month period that you would see in ENCORE. It’s not the pattern we’ve seen in the other well-controlled clinical trials in MAC lung patients that we’ve run. For example, if you think about convert in refractory MAC patients and now in the ARISE study, we saw that the patients who converted on standard of care therapies largely did so in the first 2 to 4 months of treatment. In fact, in ARISE, I think the conversion rate in the control arm stayed relatively consistent from month 3 through month 6, with the peak conversion rate occurring at month 4. So I don’t — I really don’t worry about that at all.
And that is certainly what you would hear if you talk to the KOLs that are out there who are in the disease. But we’ll see. We’ll flip the ENCORE card and see where we go. I just would reemphasize that the perception of the ARISE data is sort of universally and overwhelmingly positive. And I don’t think people feel like it’s vulnerable, I guess, is the right way to respond.
Liisa Bayko: Yes. I think — I mean, the most impressive thing is you come off therapy and you have very few people who revert back. So I think that’s just another point. But anyway, just curious how to think about that.
Operator: And your next question comes from the line of Leiyang Wang with Barclays.
Leiyang Wang: And thanks for giving us a peak the TPIP data. And on safety, [indiscernible] with incidence on in terms of irritation is pretty impressive. So on this, have you seen any GI —
William Lewis: I’m sorry, I’m having a hard time hearing you. Can you get closer to your microphone? I apologize. I want to make sure I can hear your question clearly.
Leiyang Wang: Sure. Is this better?
William Lewis: Yes. Thanks. Okay. Yes. I always have some problem with this mic. But — so anyways, so my question is in terms of safety, have you seen any GI issues in these patients? And any discontinuations that you’ve seen in either the PAH or PH-ILD patient population?
William Lewis: Nothing that is notable, but it didn’t rise to the level of discussion among the medical colleagues. So I’m not aware of anything in that arena.
Leiyang Wang: And one more question on safety as well. Given the differences in dosing, do you think the reason behind having 0 incidents of throat irritation, is that more of a kind of driven by TPIP? Or could this also be a factor in that for drugs like Tyvaso, we’ve seen even the placebo arm there is around mid-teens throat irritation, but that’s also dosed 4 times a day. So I’m just kind of curious on like what do you think is the factor driving the results on the safety side?
William Lewis: Yes. I think as I mentioned earlier, I think the fact that this drug is inhaled as a dry powder in inert form and only once a day is the key to the safety profile we’re seeing. You are correct. There are certainly placebo response rates. But as you say, if you’re taking a placebo 4 times a day and you’re affected by a disease that naturally causes cough already, it’s not surprising that you would see some of that irritation. But we’ve seen remarkably low levels, I would say, and the throat pain that is sometimes indicated and can be a dose-limiting effect for treprostinil, we don’t have that — we haven’t seen that in a way that has limited our ability to go up. So I think, once again, the safety profile here is what is permitting us to ask to go to double the current MAX dose, which is already at 640, 60% higher than the highest dose of Tyvaso in dry powder form, and we’re planning on going again double that.
