ZGNX (2020 - Q4)

Greetings, and welcome to the Zogenix, Inc. Fourth Quarter and Full Year 2020 Financial Results Conference Call. [Operator Instructions]. I would now like to turn the conference over to your host, Brian Ritchie with LifeSci Advisors. Brian Ri

Thank you, operator, and thank you all for joining us this afternoon. With me on today's call are Chief Executive Officer, Dr. Stephen Farr; Chief Commercial Officer, Ashish Sagrolikar; and Chief Financial Officer, Michael Smith. This afternoon, Zogenix issued a news release providing a business update and announcing financial results for the fourth quarter and full year ended December 31, 2020. Please note that certain information discussed on the call today is covered under the safe harbor provision of the Private Securities Litigation Reform Act. We caution listeners that during this call, Zogenix management will be making forward-looking statements. Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified by the cautionary statements contained in Zogenix's press release issued today and the company's SEC filings, including in the annual report on Form 10-K and subsequent filings. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, February 25, 2021. Zogenix undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. Now I'd like to turn the call over to Steve.

Thank you very much, Brian, and good afternoon to everyone who's joining us today. Despite the challenges we've all experienced since early in 2020, brought on by the global COVID-19 pandemic, I'm pleased to be with you here today to share details on what was a transformative year for the company. With the launch of FINTEPLA, we are providing an important new treatment option for many patients and families living with Dravet syndrome, and which is a result of many of the dedication and hard work by our team, and the clinical investigators supported us along the way. We're very pleased with the progress of our U.S. launch to date. And as Ashish will detail, we are seeing encouraging adoption by existing and new prescribing physicians and patients, as well as successful outcomes from our discussions with commercial and government payers to provide optimal access to FINTEPLA for our patients. Following U.S. approval earlier in 2020, we were excited in December to announce that the European Commission approved the MAA for FINTEPLA for the adjunctive treatment of seizures associated with Dravet syndrome in patients 2 years of age or older. We're pleased to report that as of the beginning of this month, FINTEPLA is commercially available in Germany, our first European country launch. I'll now turn the call over to Ashish for further details on how our launch is progressing in both United States and Europe. Ashish, over to you.

Thank you, Steve. As Steve mentioned, we are very excited about the positive momentum we are seeing for FINTEPLA in the U.S. and now in Europe. The physician and caregiver interest and awareness continues to grow at a consistent pace. In the face of challenges and disruptions that the COVID-19 pandemic has caused to the Dravet community and medical practices, we experienced a steady physician enrollment into the REMS program and new patient starts throughout the fourth quarter. We believe this is a reflection of the significant unmet need faced by patients and families living with Dravet syndrome and FINTEPLA's potential to provide transformational and durable seizure reduction. There have been numerous reports of patients who have achieved a dramatic drop in seizure frequency and reached near seizure freedom since starting on FINTEPLA. In Q4, our first full quarter of commercial launch in the U.S., we recorded $8.1 million in net product sales for FINTEPLA. At the end of 2020, we had 416 patients on reimbursed commercial therapy. As a reminder, as of December 31, nearly 500 care professionals had registered in FINTEPLA REMS program and making them eligible to prescribe FINTEPLA. This number is up 53% compared to the number of registered physicians in the program at the end of third quarter 2020. Also, as of December 31, over 550 patients had been prescribed FINTEPLA and were referred to the FINTEPLA REMS program, which included 336 patients who were new to FINTEPLA. Of these 336 patients, 186 were enrolled into REMS in Q4. We are seeing the referral of new patients into the REMS program at a consistent pace during the early months of 2021. In addition, all patients who were part of our U.S.-based open-label extension studies and early access program were enrolled in the REMS program by the end of Q4. As of mid-February, approximately 95% of these patients are on reimbursed commercial product and the rest are on track to receive reimbursed commercial product by the end of Q1. Given that the Dravet syndrome is notoriously refractory to multiple therapies, and as per the approved level, FINTEPLA is being added to patients' current therapies. Although the data is very limited, we see that the most of the patients being prescribed FINTEPLA are already on 3 or more concurrent antiepileptic drugs, including the branded and reimbursed CVD therapy. I am extremely proud of the work done by our team in helping patients and health care providers to access FINTEPLA. Both physicians and caregivers have provided us with positive feedback on the seamlessness and the ease of REMS enrollment and onboarding process. Currently, on average, it takes 2 to 4 weeks from the time of patient enrollment in the REMS program to the dispensing of a reimbursed FINTEPLA prescription. As of December 31, approximately 90% of patients enrolled in the REMS program had completed their required baseline echocardiograms. We are very pleased with this onboarding efficiency, which reflects successful execution by our team. With respect to access, our discussions with the U.S. payers have been extremely positive. While it typically takes up to a year post-launch to establish full coverage, we are very encouraged by the positive coverage decisions we have already received, resulting in health plan policies established in favor of FINTEPLA our coverage approval through the medical necessity process. By the end of 2020, more than 85% of patients enrolled in the FINTEPLA REMS program had received positive coverage decision and the remaining patients were in process of receiving coverage based on the timing of their enrollment. This positive trend has continued in the early months of 2021. The ongoing COVID pandemic has impacted our launch in ways similar to others in the industry. Specifically, it has had an impact on our team's ability to travel and meet customers face-to-face. To address this, we are reducing the size of some large territories and adding 4 key account managers and one regional manager to mitigate these COVID-related travel restrictions. While we cannot have a specific benchmark or a numeric assessment on how the pandemic is impacting our launch efforts, the data from Symphony Health indicates that in the antiepileptic class overall, new-to-brand prescriptions were down by approximately 35% in the second half of 2020 from their pre-pandemic levels. Now let's discuss our progress in Europe. On December 21, FINTEPLA was approved in Europe for the treatment of seizures associated with the Dravet syndrome. The approval covers all EU member countries as well as the United Kingdom, Iceland, Liechtenstein and Norway. Following the approval, we began the process of securing reimbursement for FINTEPLA in major EU countries, beginning with Germany, where we can utilize the automatic first year reimbursement process. We have also submitted pricing dossiers to begin the negotiation process in the U.K., France, Italy and Germany. To support the FINTEPLA launch in Germany, our country office in Munich area is fully staffed with the leadership, medical and sales team. We initiated our promotional launch in Germany on February 1 with the first shipments of FINTEPLA to patients occurring during the first week of February. In January of this year, we received a temporary authorization for use designation from the French National Agency for Medicines and Health Products Safety. This authorization provides access to commercial product for Dravet patients in France before pricing and reimbursement negotiations are finalized. We expect that patients will begin treatment with FINTEPLA in France during this current quarter. In conclusion, this is a very busy and exciting time for the entire Zogenix team. We are extremely pleased with the significant progress achieved in the U.S. and Europe to date. As we advance through 2021, we expect continued strong acquisition and patient demand for FINTEPLA in both U.S. and Europe. We look forward to building on this momentum and solid foundation with FINTEPLA and updating you soon. Now I'll turn the call back to Steve. Steve?

Thank you, Ashish. I'm very pleased with our commercial efforts for FINTEPLA in the United States and expect us to build on the initial success during this year as well as further advance our product launch in Europe. Let me turn now to our efforts for FINTEPLA for Dravet syndrome in Japan. As you may recall, in September, we announced positive top line results of our third global Phase III study of FINTEPLA in Dravet syndrome, which included patients from Japan. The positive results in this study will support a JNDA submission, which we expect will occur in the third quarter of this year. Upon obtaining marketing authorization for FINTEPLA in Japan, Zogenix will supply a manufactured product for commercialization by our distribution partner, Nippon Shinyaku. Now to switch to our second or potentially largest [indiscernible] indication opportunity, Lennox-Gastaut syndrome or LGS. 2020 was a year of significant progress for this key program. You will recall, in February of last year, we announced positive efficacy results from a pivotal Phase III trial of [indiscernible] LGS, named Study 1601, which will support both FDA and EMA submissions for the treatment of this severe epilepsy syndrome, where nearly all patients experience lifelong treatment-resistant seizures. More extensive data from Study 1601 were presented at the American Epilepsy Society or AES meeting in December last year. Including results that showed that FINTEPLA was highly effective in reducing generalized tonic chronic seizures or GTCs. This differentiated effect on GTCs was similar in magnitude to that observed in [indiscernible] Phase III trials. This is important because GTC seizures are recognized as a primary risk factor for [indiscernible] and sudden unexpected death in epilepsy or SUDEP. These data, combined with a novel mechanism of action relative to other approved LGS therapies have the potential to position FINTEPLA as an important treatment option for LGS patients. We're actively working on the supplemental NDA submission to seek a label expansion in United States for FINTEPLA in LGS. All required studies for the submission are complete, and we have turned our attention to study closeout activities, finalizing data analysis and conducting the integration of long-term safety data. We expect to submit the supplemental NDA in the third quarter of 2021, and to follow that with an MAA submission in Europe by year-end. Late last year, we were also very excited to see the promising initial results of FINTEPLA in CDKL5 deficiency disorder or CDD, from investigator-sponsored trial presented by Dr. Anda Vinski at the AES meeting. The study results showed that patients experienced a 90% median monthly reduction in generalized tonic crown seizure frequency, and a 55% median monthly reduction in tonic seizure frequency when FINTEPLA was added to their existing antiepileptic drug regimen. Based upon these highly encouraging results, in January, we announced that we were moving ahead with a Phase III trial of FINTEPLA in CDD. We anticipate meeting with FDA and EMA next quarter to obtain advice on the program, which we believe will allow enrollment to begin in the second half of the year. Now I'd like to discuss MT1621, our late age investigational therapy for the treatment of a mitochondrial DNA deficient disorder, called thymidine kinase 2 deficiency or TK2d. The MT1621 program is advancing with several studies ongoing. Study 102, the prospective safety and efficacy study has enrolled 47 patients. Study 107, the chart review study that captures data on TK2d patients treated with pyrimidine nucleosides outside of our studies also continues to progress. Our enrollment has begun in Study 106, a renal impairment study to support chronic dosing. We continue to plan through an NDA submission in the first half of 2022, and intend to submit for European approval soon after the U.S. submission. In parallel to the development work, we have initiated various diagnostics screening projects to identify more TK2d patients with clinical sites in the United States, Italy as well as other countries. Finally, we announced in December an early-stage partnership with Tevard Biosciences, a company pioneering tRNA-based gene therapies to discover and develop novel treatments with a goal of treating the underlying causes of disease for Dravet syndrome and other genetic epilepsies. This collaboration reflects our long-term commitment to continue seeking solutions to help transform the lives of rare epilepsy patients and their families, who we recognize face additional important unmet needs beyond seizure control. In summary, last year was an incredibly busy and productive year for Zogenix, as we continued to grow as a commercial stage rare disease company. With that, let me hand over the call to Mike for the financial review. Mike?

Thank you, Steve, and good afternoon, everyone. Today, we issued a press release announcing our business and financial results for the fourth quarter and full year-end December 31, 2020, which I'll now review. We recognized $8.5 million in revenue during the fourth quarter of 2020, and this was a result of $8.1 million in product sales of FINTEPLA in the U.S. and $0.4 million related to our exclusive distribution collaboration with Nippon Shinyaku for FINTEPLA in Japan. We recognized $1.9 million in revenue for the corresponding period last year. R&D expenses for the fourth quarter, $36 million, essentially flat as compared to the $35.8 million recorded in the corresponding period of 2019. SG&A expenses for the fourth quarter ended December 31, 2020, totaled $29.2 million, compared with $18.7 million for the fourth quarter of the prior year. The increase of approximately $10.5 million was primarily driven due to the continued investment related to the launch of FINTEPLA in the U.S., which began in the third quarter of this year, and for preparations related to our commercial launch in Europe, which is now ongoing. Net loss for the fourth quarter ended December 31, 2020, was $70.2 million or $1.26 per share, and this compares to a net loss of $56.1 million or $1.26 per share in the fourth quarter ended December 31, 2019. We ended the year with a strong balance sheet with cash and cash equivalents and marketable securities to $505.1 million. Please note, we intend to file our 10-K premarket on Monday, March 1, 2021. And with that, I'll now turn the call over to the operator to start our Q&A session. Operator, can you please open up the line for questions.

[Operator Instructions]. Our first question is from Paul Matteis with Stifel.

So a couple on -- one on the quarter and then just a couple on some of your 2021 commentary. On the quarter, was there any material changes in inventory? We're just kind of trying to get to this revenue number based on the patient data that you provided. And then separately, 2 questions on 2021. One, so Ashish, I was wondering if you could clarify and expand on any of your comments? It sounded like you kind of alluded to basically saying so far in 2021, the pace of patient adds has been pretty similar to what you observed in 4Q. And then separately, one of the confounding things with modeling average price quarter-to-quarter is that EAP or kind of patients in the [indiscernible] extension may already be passed the titration. So I'm kind of wondering now that you're through more of that, what's your expectation for the cadence of average dosing FINTEPLA this quarter and kind of the following quarters relative to what we saw early in the launch?

Thank you, Paul. I'll just start with revenue and how that reflects back to patients who are on drug. Just recall, we have a specialty pharmacy distribution for FINTEPLA. So in reality, our sales reflect drug that's being dispensed to patients. There's really not an inventory build up. And I think the other questions you had, you asked Ashish to address, which I think is a great -- it's good to do that. And Ashish, if you want to add anything to what I just said, please go ahead and do that as well.

Sounds good. Paul, yes, what Steve said is correct in terms of the inventory. There is no inventory -- as we just have one specialty pharmacy, and everything that you will see in the sales is straight to the patients. In terms of the commentary on the pace of patient-add similar, that is correct. We see similar patient adds as we have seen in the past 2 quarters. And in terms of modeling average dose, again, it's very early. But one thing I would say is all the clinical trial and early access patients are now transitioned, almost all of them, 95% of them. And their dose on an average was 0.48 with a weight average weight of 34.5 kilogram. So I think that will stay consistent going forward. And the new ones that are coming in, we are seeing similar dosing escalation schedule, somewhere between 3 and 6 months. And again, the data is so small in the first 3 months, it's really difficult to say if that trend will continue. But from a modeling perspective, I think, if we use the same trajectory of 3 to 6 months, that will be consistent with what is being seen.

Okay. Can you -- are you able to comment at all, Ashish, I'm just kind of, I guess, in the fourth quarter, are most of the patients who are on therapy already past the titration because of this? I don't know if you're able to clarify that, but that would be helpful.

Yes. So the one thing I'll tell you is that if you take, say, 3 to 6 months, so anybody who would have come in the pipeline say sometime in October would be at their optimal dose, say by this month. So that's the cadence if you want to model it that way.

Just one thing to add. The label does inform by titrating on a weekly basis. But what we've seen on the unexpanded or early access program, I think, is true for other drugs that use to treat epilepsy. Physicians tend to titrate more slowly that because they're adding the drug to an existing regimen drug. So they tend to go there more cautiously, which is why we modeled out 3 to 6 months that Ashish described.

Our next question is with Marc Goodman from SVB Leerink.

For 1621, can you just review where we are with some of the gating issues to file? I know in the past, you've talked about -- there was a nonclinical talks in dog study, there was reproductive talks. All the other things that you had not mentioned in your prepared remarks. And then maybe you could just give us a sense on FINTEPLA just are all patients pretty much staying on drug so far? I mean, I know it hasn't been that long, but have you noticed or heard of any dropouts at this point? I mean, it's been such a short period of time, but I'm just kind of curious, how retention was going so well? And the feedback just from the patients so far?

Yes. Marc the discontinuation rate is very small. So -- but I also want to caveat that with it's still relatively early in the launch, but we're certainly encouraged with what we're seeing today. And I think it sort of reflects that what we've seen both in our early access program and also in our long-term open-label studies where we saw a very robust efficacy response and a very low discontinuation rate. So hopefully, we'll continue on that same trajectory. Ashish provided some feedback in his prepared remarks, but we are seeing a curing of our patients are doing remarkably well, that have been new to FINTEPLA, were not part of our clinical trials and seeing the same response as patients saw in our clinical trials in terms of a dramatic reduction in seizures, recall that in our randomized controlled trials, we saw a dramatic reduction in seizures even during the titration phase of FINTEPLA. So the speed of onset is very fast, and we've seen a very durable response thereafter. So far, we've seen the same thing patients who are coming onto commercial product who are new to FINTEPLA. With respect to MT1621, all the tox studies are on track. So there's really nothing news worthy there. We're just continuing what we need to do in order to get everything ready by the end of this year for a submission in 2022, as we talked about.

So no issues with COVID slowing anything down?

Not on the alternate side. We continue to have to work around COVID on our clinical studies, particularly Study 102, which is the prospective [indiscernible] and efficacy trial. We had some periods last year because of the ban on international travel, patients couldn't get to study sites. But we've been able to, for the most part, get around that by them going to local offices or hospitals where they could get some of those assessments. But that's really been the biggest factor in that program -- it's really around Study 102.

Our next question is from Yatin Suneja with Guggenheim Partners.

Just a couple for me as well. Can you remind us what gross-to-net is where you currently are? And how should we think about GTN at the end of this year? And then in terms of the -- I mean, I understand you are early in the launch. Maybe talk about the type of patients you are seeing, do physicians still have to go through generic Epidiolex before they can start on FINTEPLA? Can you maybe give us a little bit flavor on the patient population?

Thanks, Yatin. Mike, maybe you can address the gross-to-net question. And then Ashish, you can address Yatin's second question about the type of patient coming on to therapy.

Sure. Yes. Most of our sales now, obviously, are in the United States Yatin, so -- we're in the beginning of launch gross-to-net roughly now is a little bit under 20% in the teens. So to speak, it will inch up towards that 20% number throughout the year. It will be a contribution of mostly the United States for this year and some in Europe.

Ashish?

Yes, Yatin, for your second question regarding the type of patients. Yes, as I said in my prepared remarks, I think, the patients we are receiving is typical [indiscernible] patients who already is on 2 or 3 or more different therapies. What we have seen is the majority of the patients, if not -- actually, all of the patients are on at least 2 products or more already, and majority of them are 3 and more. And in terms of them getting added FINTEPLA has been the [indiscernible]. And FINTEPLA just gets added, and that is per the label. And in that, we haven't really seen anything which will say that, hey, you have to try one product or the other product. Most of the policies that we have seen are primarily to the label, which is prescribed by the neurologist, try at least one antiepileptic products, enroll in the REMS program, do your ECHO and dose not exist -- dose not exceeding 26-milligram per day or 17 if you are still on FINTEPLA. One thing to mention is that the policies that we have received both on the Medicare as well as on the commercial side, the FINTEPLA is on parity with the other branded anticonvulsant drugs, which is really positive for us and the patients.

Got it. I just have one more follow-up. This is regarding the weight. This is regarding the price. Can you maybe remind us what percent of Dravet patients do you expect to be on stiripentol plus clobazam? Because I think those patients do receive -- I think half the dose was a little bit lower dose.

Yes. So stiripentol is -- in terms of usage of the product is very low, is what we have seen. In our clinical trial, you have seen a lot of them. And in the early days, that percentage is extremely low. Again, it's an early time. So maybe we'll be able to give better number in another 3 or 4 quarters once we have a little more robust set of data. But for a modeling perspective, I think, right now, the number is pretty low.

Our next question is with Jason Butler from JMP Securities.

It's Roy on for Jason. Just a couple of quick ones. You guys mentioned before essentially a Phase II basket trial contingent on COVID. Just wondering if you have any thought -- updated thoughts on that? And on 1621, Steve, I think you mentioned a couple of sites in the U.S. and Italy to identify additional patients. Just wondering if you could provide any more color on that. It sounds like the sites are open. Are they -- have they found any patients? And what are they doing to look for patients?

Thanks, Roy. Phase II basket trial. As you just recall, we paused on that study last year because of the COVID pandemic and an inability to really get study sites up and running as well as not wanting to put anybody in harm's way with respect to either our team or patients being participating in a study. But we decided this year on the basis of some investigator studies that continued last year to really prioritize a Phase III program in CDKL5 deficiency disorder. And it's interesting that the whole intent of Phase II basket trial was to demonstrate where the product may work that would inform us whether or not we could start a more formal development program. But we got back exact results out of the ISS they deducted back off the [indiscernible]. The data was so powerful. We really wanted to move forward a Phase III program. We'll continue to support investigator-initiated studies again to look for signal. And we haven't said we're not going to do the Phase II trial, but we're deprioritizing that at this moment in time in order to put all our best efforts into starting the CDD trial. 1621, it's 30 days with respect to what we're doing to identify patients and looking at -- we have a number of different initiatives that we're working on right now around sort of screening projects, diagnostic advisory boards, market research, United States and Europe, potentially partnering with diagnostic partners. And also running some studies to look for patients in various countries. All that is going well, and we do expect to have a better understanding of the overall patient prevalence by the end of this year and certainly in plenty of time before we submit the NDA for MT1621. I'd also make point that we are working with advocacy groups and mitochondrial diagnostic groups to really advance and support disease awareness, and we think that's critically important. And to ensure that we can get a diagnostic test, particularly to the -- understand the neuromuscular myopathy disease panels. We see that as critically important in order to really understand the overall patient prevalence.

Our next question is with Difei Yang with Mizuho securities.

Just a couple on FINTEPLA. Would you be able to comment on how many unique prescribers that have prescribed FINTEPLA, which I mean among those doctors who are REMS certified? And then beyond that, if there's a typical lag time between the certification of REMS to the first script written? The second question is around, how should we think about the uptake trajectory in Germany? Would it be somewhat similar to the U.S.?

Thanks, Difei. I going to ask Ashish to address your questions.

Difei, in terms of unique prescribers, we haven't broken out that number. But what I can tell you is that we are receiving prescriptions from the key centers that is the 450 physicians that we talk about as the core group, which treat around 80% of the [indiscernible] patients. So majority of them are part of this group, and they are prescribing. And we have also received prescriptions from physicians in the community setting who may have 1, 2 or maybe 3 Dravet patients and we have received prescriptions from that too. But mostly it is a lag time. It is all dependent on the physician and their ability to get the patient and get the patient through the entire process. And as we said -- commented earlier, I think, with the COVID situation, what does happen is that in many places where there's reluctance of families to switch the medication due to fears of concern. And this is what they had experienced in the past, especially things like diarrhea with some of the other products, which related -- which led to potential hospitalization. And in COVID situation, they really don't want to take that chance. And then we also have a situation with this rolling state-by-state shutdowns. And in January, we have a lot of places which were closed, and that reduces the access. And that kind of contributes in terms of when the physician will be able to get a patient and be able to put through the process. On the trajectory to Germany, we got to divide it in 2 things. One is the patients who are on the early access program and the clinical trial and then the new patients that are coming in. Again, it's been just 2 weeks. So it's very difficult to talk about the trajectory. But one guidance I would say is that by law, in Europe, once the product is approved and is reimbursed in these countries, you have to transition pretty quickly. So we expect that the early access patients and the clinical trial patients will be transitioned to the commercial product anywhere between 2, 2.5 months to 6 months, again, depending on the timing and when they are able to do their end of the study visits. But the early access program should have in a span of 3 months. That's the timeline we have seen with a lot of other products. And I have no reason to believe it will not be the same for FINTEPLA.

Our next question is from Tazeen Ahmad with Bank of America.

Maybe one question on Dravet and one on upcoming for LGS. So for Dravet, Steve, I was just curious as to how your team is thinking about -- of the early months of the launch, what gating factor do you think is the most important right now to clear in order to meaningfully accelerate the pace of the launch? Is it doctor awareness? Is it REMS? Is it the COVID environment? Is it ECHO? Is it something else that you've been able to observe in the early part of this launch? So any kind of color on that would be great. And then as it relates to LGS and the potential for sales next year from that indication. Can you talk about any kind of differences there might be for LGS patients as it relates to weight or being underweight relative to Dravet patients? And how that might translate into what an average dose might be for an LGS patient, if it happens to be the case that they tend to be underweight a little bit more often?

Thanks, Tazeen. Why don't I take the LGS questions straight away, and then Ashish, maybe you could take the question that Tazeen had about a launch in Dravet. With respect to LGS, our clinical trials did include more adults, actually included adults. So on that basis, the average age and also the average weight in those studies was higher than it was in Dravet. And as a consequence of that, in the high dose group, where we saw a highly significant difference versus placebo. We had a fairly large proportion of patients who are on the maximum dose of 26 milligrams per day. So we expect that will also be the case for the ultimate commercial product. But because this is a disease that's recognized in adults as well as children, you'd expect the average dose to be higher because the average weight -- so the average dose is higher because the weight is higher because the patients are older. Hopefully, that addresses your question. If it does then, Ashish, maybe you can take the other part of Tazeen's question.

Thanks, Steve. Yes. Tazeen, in terms of the gating factor, as I said in my prepared remarks, I think our ability to execute once there is a prescription, and help the patients through the ECHOs, through the reimbursement process. I'm really proud of what the team has achieved and the investments we have done. I think the biggest wild card right now is the COVID environment. And how that impacts and how we are seeing that getting impacted on 2 fronts. One is our team's ability to travel and see customers face-to-face because you can do only limited things remotely, and that does take time. And also for the customer -- for the patients and the families and their reluctance in accessing the medical facilities during this COVID environment. And I think that's what we all say is the biggest one at this point in time. And it's corroborated by the data that I shared in the prepared remarks, where we saw in the second half. When you look at -- all the antiepileptic products, we saw the NBRx's down by almost 30% -- 35%. And we believe that and we have full confidence that as the thing starts opening up with the increased vaccination, we are already seeing a lot of facilities opening up, a lot of places where we did not have a face-to-face access, we are now getting face-to-face access. So I can just see this going up in the future quarters.

Okay. So if the predictions about going back to semi levels of normal are true about the second half of the year, should we expect to see meaningful acceleration in script trends in 2H based on what you said?

We should, but I don't have a reference point to say what it will be. Because we launched during the COVID time. So again, we will be in this launch more for at least a year or more, because there are certain physicians we haven't been able to reach in face-to-face. We have done that on the Zoom. So that's something I think we will continue to see. So it's difficult to give a guidance exactly what that will be because there is no benchmark at this point in time, at least, for our case.

Our next question is with Tim Lugo from William Blair.

You mentioned the effect of FINTEPLA on GTCs as being one of the kind of signals of effects physicians are honed in on. Are you going to be able to draw that out in the label as you prepare for the filing? And with CDKL5 kicking off in the second half of the year, is that a study which we should be able to see data from in 2022, yes, 2022?

Yes. Tim, with respect to the impact on GTCs, it wasn't, if you like, a prespecified endpoint, it was a post hoc analysis. So unlikely that you'll see that information specifically in the label. However, we will -- we're making the physicians aware all that differentiated effect, obviously, to publications, and we'll continue to do that. And interesting that this effect on GTC, we're now seeing in 3 different epileptic syndromes, starting the Dravet, than LGS and also in CDKL5. And that dramatic impact on GTCs is actually reflected -- in some very important animal data we have as well. And it's really good correlation to what we've seen in experimental animal models and what we've actually observed in patients. So that's gratifying. In terms of your second question, Tim, would you might just remind me again, what exactly...

Sure. Yes, CDKL5, are you -- should we be able to see data coming out of that in 2022? And maybe just general broad strokes what the study will look like? If you're going to use 0.4 and 0.7 doses? Is it going to be 250 patients? Is that -- is it going to be kind of similar to historically run trials?

Yes. We're still finalizing the protocol, and we need to obviously share that with FDA and EMA, as I mentioned in my prepared remarks. So probably it's too early to tell you exactly what the trial design would be like. But I think it's safe to assume it will be very similar to what we did in Dravet syndrome. And because of the high effect size that you did see in the open-label trial, we do expect that the sample size will be the same as in Dravet so around 40 per arm. And so I think that sort of covers as much as I can say about the protocol for now. But obviously, we'll have more information as we go through the next several weeks. In terms of will data be available next year. It's really too early for me to predict that. We haven't started the study yet. We don't know what the enrollment rate is going to be. So it's hard for me to project when we would get data. But obviously, it's when we get the study up and running after this year, we see that trend, we can more appropriately inform investors and when they should expect to see data.

[Operator Instructions]. Our next question is with Danielle Brill from Raymond James.

I have a quick follow-up to a prior question. Ashish, you mentioned that the EAP patients in Germany will convert to reimbursed drug pretty quickly. Can you remind us how many patients you have in the EAP program in Germany? And then I'm also wondering what we should expect in terms of use in France in 1Q?

So, Danielle, I think, from EAP patients number in Germany is approximately a little less than 100. So I think that's the number we will expect to convert pretty quickly. In France, it's very difficult to give the usage primarily because the temporary authorization to use is primarily for physicians to apply and get the reimbursement and then start the process. So this is something which we cannot promote. We cannot talk about and we are not going to do that. But we just got to make it available. And if the physicians have a patient that they need to put on, we do have a program they can reach to our medical team or they can reach to the central team. And through that, they will access the product. So -- but it's very difficult to project what utilization will be. But what we do know based on the interest, and that's why we went ahead and asked for this authorization, we do expect that there will be patients who will be accessing the product through this facility.

Our next question is with Paul Matteis with Stifel.

I was just looking back at our notes, and I might have this wrong. But I thought the LGS submission was supposed to be first half or second quarter, and it looks like it's third quarter now. Am I right that, that is a push? And is there anything else to that, that you could kind of help clarify?

Yes. Paul, it has been pushed out. And it's a [indiscernible] basically [indiscernible] all the studies are complete. So we're now in the data analysis mode. And as part of the preparation for the sNDA we have to rely upon outside parties and vendors to do site visits before study closeout as well as do a lot of analysis for us. On the basis of that, we've sort of under the timelines that we're receiving from CROs. I think it's best to estimate that we'll be going into the third quarter for the submission. Clearly, we are focusing on ensuring that we can submit the highest quality sNDA as we can. And if that moves into third quarter, which we predict it will then I think that's the best course to take.

Okay. All right. I appreciate it. Do you have any expectations for the duration of the review for the sNDA?

Well, it's a 505(b)(2) supplement. So we will either be priority review, which is a 6-month review clock, or it will be a standard review, which is 10 months. We will be doing our best to justify why the FDA should be awarding a priority review for this. But at the end of the day, it's something which they need to determine and decide upon as opposed to than we can. But -- so it's either 6 or 10 months, Paul.

Ladies and gentlemen, we have reached the end of our question-and-answer session, and I would like to turn the call back over to Steve Farr, CEO, for the closing remarks.

Well, thank you very much, operator, and thank you to all of you for joining us on today's call. We're obviously very pleased to share our progress over the past year. We've transitioned now to a commercial stage rare disease company. We are looking forward to further growth in the year ahead and for providing further updates on our commercial and clinical activities throughout 2021. Thanks again for joining us on our call today, and enjoy the rest of your day. Bye-bye now.

This concludes tonight's conference. You may disconnect your lines at this time. Thank you for your participation.