We clearly think we have an opportunity to see it early given the specificity of PDC-E2 and the specificity of this therapy. That’s why we have a 120-day look, but we’re certainly going to learn from that. And that’s why we have this combination of need, meaning to demonstrate a T cell response and the liver function improvement. So certainly, the different mechanism is important to understand. And also, it’s very important to realize that we’re actually going for a very disease-modifying approach, not just moving bile flow through the liver better, which is a biomarker for potential benefit for liver disease.
Sravan Emany: So on your guidance question, Look, I think on high level, I’d say again. One, I think from our perspective, and it’s — the guidance we gave for 2024 accounts or the mix we anticipate in 2024, it’s our 2024 guidance. We expect to still see high single-digit prescription demand growth, and I think the decline is as stated, based on our overall annual guidance. This is a onetime adjustment. We’ve been pretty good as a brand over the last several years and anticipating with our estimates as with respect to what that mix is in a channel. Channel mix is pretty fluid and predicting LINZESS net sales can move in a positive or in a negative directions has always been true, but we’ve been pretty good about it over the years.
And I think at this point, we’re still expecting to deliver a mid-single-digit decline, as I said before, and that’s predominantly driven by the onetime out-of-period adjustment. Outside of that, I think we would have been in line with guidance for the full year.
Mohit Bansal: Got it. Helpful. Thank you.
Operator: Your next question comes from the line of Tim Chiang with Capital One.
Tim Chiang: Thanks. Mike, I was just looking back at the secondary endpoints from the STARS study, do you guys plan on showing, I guess, the earlier week data from the CIC patient population at DDW, especially with the secondary endpoints that you didn’t need statistical significance on.
Mike Shetzline: Yeah, Tim. If you’re referring to sort of specifically things like enteral autonomy or things you might see at 24 weeks versus the key secondaries at 48, the answers is yes. And we certainly think that data further supports our conviction of good efficacy in both stoma and CIC patient populations. So yes, we plan to see that — to have that at DDW as well as sort of the decrease in parenteral support volume and the relative change from baseline in that capacity as well. The DDW have planned oral presentation. It’s obviously still in development, but we have a lot done on it already, and it’s very data heavy. I think you’ll be very impressed with the amount of data. We’re certainly clearly very excited by it because it clearly supports our conviction that the drug is approvable and works in both colon in continuity and stoma patients. So we really are looking forward to sharing that more broadly with the community.
Tim Chiang: Mike, just one follow-up. Why is the placebo effect so high in these studies? Because I noticed on your third secondary endpoint, the placebo rate was almost 44%. Can you comment on that?
Mike Shetzline: Yeah. I mean I think the key to realize there is that the primary endpoint placebo response was 12.5%, right? And that’s the key driver for the study’s positivity statistically and the path to approval. So I think that’s a key thing to keep aware of. The other thing to realize is the 48 week endpoints never had been tested in a GLP-2 therapy before. And there can be a tendency for placebo response to change during a clinical trial. And it’s also important to realize that what we’re actually talking about here, placebo response is different at 24 weeks on the primary endpoint, meaning it’s the relative change from baseline versus the one day off, which is the third key secondary, you alluded to, that’s 44%. And then in addition, we instituted a new design in this trial, which is the winning algorithm.
So that’s clearly played forward through the study. We’re going to analyze that data real cost carefully to make sure we understand it. But there is a potential opportunity for the winning algorithm, which would be in place for both placebo and drug-treated patients could elevate the placebo response with later time points in the study. Because early in the study, it might be more volume-driven, whereas as people wean, then you may fall under the year an output threshold of 10% and you make it exposed to weaning out. We’re still looking into that, but that’s clearly one thing on the list to figure out if that’s what made the 48 week endpoint, we’ll see the response so high. And one final point to realize even though the placebo response was high at the third key endpoint on the CIC population, APRA was still numerically superior.
So when we get to this sort of aspect of approvability, that fact that APRA still did numerically better will be a positive in terms of not looking at it like we’re worse than placebo or things like that. That’s not the case. And then given the things we talked about on the primary and the first key secondary being positive in the whole population, we clearly think that bodes well for a high probability of success for approval for both populations.
Tim Chiang: And maybe just one last follow-up, Mike. Are some of these items, do you think that you could get them on the label? Because I think those would be important, especially in the colon-in-continuity patient population.
Mike Shetzline: Yeah. I think we’re going to work to get everything in the label we can. We certainly think the drug works very well in both patient populations. One of the reasons we included those additional secondaries was for exactly that reason. However, that challenge is higher now, obviously, because they didn’t meet statistical significance. But as I mentioned, both are numerically better. So we certainly have a strong confidence for approvability.
Tim Chiang: It’s okay. Great. Thanks.
Operator: Ladies and gentlemen, that concludes our Q&A session and today’s call. Thank you all for joining. You may now disconnect.
