So, we have no reason to believe that that endpoint will not be appropriate or sufficient, but the Hi-DEF is also a good endpoint that will add additional information about how Dalzanemdor affects patient functioning.
Barry Greene: Yes, and Laura, it’s a really great question. As you’re well aware, with Dalzanemdor, we’re forging new pathways here. There’s not been a medicine specifically approved for cognitive impairment in Huntington’s disease. It’s a really huge unmet need. And given the orphan nature, again, data matter here, but we believe there’ll be tremendous flexibility in working with the package here.
Operator: We’ll move to the next question from Neena Bitritto-Garg with Deutsche Bank. Please go ahead.
Neena Bitritto-Garg: Hey, guys, thanks for taking my question. I just wanted to go back to the ZURZUVAE launch. So, just looking at some of the third-party script vendors, so specifically IQVIA, it looks like there’s a decently high capture rate versus what you’ve reported in terms of dispensed scripts. So, I’m just wondering if you can kind of comment on that and if we should look at those third-party vendors moving forward. And if you can talk at all about what you’ve been seeing kind of on a week-over-week perspective on scripts so far this quarter, that’d be great too. Thanks.
Barry Greene: Yes, Neena, let me start, and I’ll turn it over to Kimi to talk specifically about IQVIA. So, again, what we’ve reported out in the fourth quarter was roughly 10 days of commercial availability where moms could access healthcare providers to advocate for ZURZUVAE. We’re not really talking about the data specifically in January and February, other than the fact that we’re seeing positive trends continue. But Kimi, you want to talk more about the IQVIA data?
Kimi Iguchi: Sure. The launch is trackable through IQVIA. However, the data may not provide a complete picture of ZURZUVAE utilization. What you see in the data is shipments to patients, not prescriptions, and then data does lag by about a week. The data, I’d say, is directionally correct, but not precise. There are things like free goods that might not be captured in certain cases, or there might be specialty pharmacies we contract with that might not be covered. So, again, I’d say the data is directionally correct, but not precise.
Operator: We’ll move to our next question from George Farmer with Scotiabank. Please go ahead.
George Farmer: Hi, good morning. Thanks for taking my question. Back, still on the ZURZUVAE scripts, I mean, Biogen reported $2 million in sales in December, and you guys are reporting 120 scripts written over the same period. Just kind of back the envelope math suggests that all those scripts generated revenue. Are we thinking – is that the right way to think about this? And maybe you can comment on whether there were other scripts that didn’t get filled and how many – perhaps there were some other scripts that were part of the free drug program as well. Is that the right way to think about this?
Barry Greene: Yes, George, I’ll take that and thank you for the question. So, it’s important. Let me reiterate sort of the supply chain, if you will. When specialty pharmas need to stock the drug, they put an order in. When that order is sent to the specialty pharma, that’s where revenue comes in. So, revenue is drug into specialty pharma. The drug gets pulled from specialty pharma when a healthcare provider, and this is done mostly electronically, writes a script. That script automatically goes to specialty pharma, who does insurance verification, other backend processing. And when all that’s done, and it can happen in 24 to 48 hours, that prescription then is shipped to the patient. The IQVIA data that Kimi talked about are those shipment data.
So, that’s what you can see. We’re providing color on script, which as Chris mentioned, we’ll provide for the first couple of quarters, but likely we’ll drop that metric. So, it’s not a direct correlation. Now, the fact that we saw 120 scripts is exciting and encouraging in a very short period of time in December.
Operator: We’ll move to our next question from Sumant Kulkarni with Canaccord Genuity. Please go ahead.
Sumant Kulkarni: Good morning. Thanks for taking my question. Now that you’ve probably had some patients finish their 14-day course of therapy, what sort of real-world feedback are you getting from patients on how quickly ZURZUVAE may be working in the real world, and how patients might be feeling after the treatment, and if there are any unexpected positives or negatives you’ve seen post dosing?
Barry Greene: Yes, Sumant, great question. So, the early feedback we’ve heard from the field has been positive and we’re highly encouraged by the anecdotes of the early patient success stories. Of course, a bunch of anecdotes don’t add up to data. We’re also pleased that we’re hearing back from many healthcare providers, including OB-GYNs, primary care, and psychs, about ZURZUVAE. And in general, what we can say is in the real world, ZURZUVAE is performing, as we saw in clinical trials. And that is taken at night, rapid onset of options. 50 milligram is being prescribed and patients are completing the 14-day short course treatment.
Operator: We’ll move to our next question from Akash Tewari with Jefferies. Please go ahead.
Phoebe Tan: Hi, this is Phoebe on for Akash. Thank you for taking our questions. Biogen mentioned on their Q4 call yesterday that they aren’t sure if the initial set of prescriptions represents the bolus, given that ZURZUVAE was approved in August and then only launched in December. So, do you feel like demand may be a bit choppy out of the gate, and has there been – or has there been any increased demand in January? Additionally, just wondering why you didn’t guide to ZURZUVAE revs for 2024, and do you plan to guide in later quarters? Thank you.
Barry Greene: Yes, Phoebe, thanks for the couple of questions. I’ll start. I’ll ask Chris to comment more and then Kimi can talk about guidance. So, PPD is not a warehousing effect-type disease. We’re seeing tremendous demand continue into the early part of 2024. So, we can confidently say, there’s no warehousing here. We’re seeing demand continue. And the numbers, while encouraging, are really small relative to the half a million women a year potentially suffering from PPD. So, there’s a long way to go to help many of these women. Chris, you want to talk about through the early launch dynamic, and then maybe Kimi can talk about guidance?
Chris Benecchi: So, so what we’re hearing from clinicians out of the gate, and Barry touched on it in his opening remarks, we’re seeing strong positive performance coming from ZURZUVAE in and around prescriptions, prescribing patterns, patient support and coverage. Those are all areas that we’ve talked about significantly. But again, specifically around physician utilization of the medication, we’re seeing balanced prescribing across physician types, OB-GYNs and psychiatrists with a core group of PCPs that are also writing this medication as well, too. Those are clinicians that actually have women in front of them that are presenting in the moment with the signs and symptoms of PPD. These are not patients that have been waiting for the medication for a sustained period of time, as you might see in other categories.
So, we really believe here, and as Barry said, that this is a category where there is not warehousing effect. And we’re going to continue to make sure that we do all that we can through our sales organization and through our omnichannel efforts, in particularly digital, to provide physicians with the education, the information, and the support to prescribe ZURZUVAE in the moment when these women come through their offices. Yes, and before Kimi jumps in with guidance, Phoebe, let me highlight something that Chris said earlier on. We’re early in the launch, but we’ve already seen the paradigm shift from a healthcare provider suspecting depression and referring to a healthcare provider diagnosing and treating. We’re really in launch. So, that’s already a paradigm shift we’re seeing among these healthcare providers prescribing.
That’s highly encouraging.
Kimi Iguchi: On, on the revenue guidance, to start with, we’re pleased about the encouraging early launch of ZURZUVAE, as you’ve heard from our call. But we believe we need to take some additional time to better understand the dynamics around the uptake. We plan to communicate additional updates related to the commercial of ZURZUVAE in due course.
Operator: We’ll move to the next question from Yatin Sunej with Guggenheim. Please go ahead.
Yatin Sunej: Thank you for taking the question. Specifically on the PRECEDENT study, so the primary endpoint is the Wechsler Intelligence Scale. Could you help us understand like what is the relevance of the scale, number one? What do we see from a placebo perspective for this study? I understand maybe you’re not willing to go there and tell us what data you would like to see, but just help us understand how placebo perform on this scale so that we have a database line. Thanks.
Barry Greene: Yes, thanks for the question on Dalzanemdor and the PRECEDENT study. Laura, you want to take that?
Laura Gault: Sure. So, with the PRECEDENT study, we included the WAIS-IV coding as a primary endpoint based on information we had gotten earlier in our development program for Dalzanemdor. As I mentioned earlier, in the Dalzanemdor program, we conducted small probe studies in Alzheimer’s, Parkinson’s, and Huntington’s disease. And in each of those studies, we saw signals of efficacy in cognitive domains of executive function and learning and memory. And the WAIS-IV coding was a scale that we used in those early studies to detect that treatment difference. So, what we are doing now in the PRECEDENT study is using that as a primary endpoint, recognizing, of course, that it is not clear whether that could be a standpoint. So, the study also includes a number of other measures of cognition, including the MoCA and the SCOPA-Cog. And so, we will be looking at directional effects on those endpoints to make decisions about moving forward.
Chris Benecchi: And Laura, if I can add just one thing. I think across all these studies, it’s important to recognize that we are looking for an improvement upon baseline, not necessarily a slowing of change. And I think that will also factor into how we look at the differences versus placebo.
Operator: We’ll move to the next question from Vikram Purohit with Morgan Stanley. Please go ahead.
Vikram Purohit: Hi, good morning. Thanks for taking our question. We had one follow up on your initial read of prescribing behavior. So, I believe you mentioned in your opening remarks that there were certain providers who had written multiple prescriptions for ZURZUVAE in the first 10 days of the launch. So, we were wondering if there are any common characteristics across these providers or their patient bases that stick out to you. And more generally, if this gives you a read on how concentrated or not the prescriber base for ZURZUVAE could be throughout 2024. Thank you.
Barry Greene: Yes, thanks for the question. I’ll take that. I’ll ask Chris to add if there’s any additional color. So, we’re actually seeing broad prescribing across the United States among, as we said, psychiatry, OB-GYNs, and small numbers, but primary care. I don’t know that there’s trends that are indicative of multiple prescribers other than a prescriber that we assume had a positive experience, sees another patient suffering from PPD, and believes that ZURZUVAE is the right drug to reach for. As you know, our goal is for ZURZUVAE to be the first line treatment for women suffering for PPD, and we’re excited and encouraged by the early progress to date.
Operator: We’ll move to our next question from Marc Goodman with Leerink. Please go ahead. Yes, good morning. Two questions. First, for 324, can you remind us how long the drug is active, such that taking at night will still have activity throughout the next day? And then a question just on 718, can you talk about the rationale for using oxysterol in Parkinson’s? I understand that Huntington’s patients have low levels, but I didn’t understand why it makes sense in Parkinson’s. Thanks.
