Greetings, and welcome to the Alkermes conference call to discuss regulatory update for ALKS 3831. My name is Melissa, and I'll be your operator for today's call. All lines have been placed in a listen-only mode. If you should require operator assistance during the call, please press star zero on your telephone keypad. Please note that this call is being recorded. Now I'll turn the call over to Sandy Coombs, Vice President of Investor Relations. Sandy, you may begin.
Thank you. Welcome to the Alkermes plc conference call to discuss the regulatory update for ALKS 3831. With me today are Richard Pops, our CEO, and Heather Faulds, our Senior Vice President of Regulatory Affairs. Before we begin, let me remind you that our discussions during this conference call will include forward-looking statements relating to, among other things, our expectations concerning next steps in the regulatory review and potential approval of ALKS 3831. These forward-looking statements are neither promises nor guarantees and are subject to a high degree of uncertainty and risk. Please see our press release issued this morning and our most recent annual and quarterly reports filed with the SEC for important risk factors that could cause our actual results to differ materially from those expressed or implied in the forward-looking statements.
We undertake no obligation to update or revise the information provided on this call as a result of new information or future results or developments. After our prepared remarks, we'll open the call for Q&A. Now I'll turn the call over to Richard.
Thank you, Sandy. This morning, we announced that FDA issued a complete response letter related to the new drug application for ALKS 3831. The items that led to the CRL relate only to the manufacturing of 3831 at our Wilmington, Ohio, facility, and we believe we have a clear path to resolution of those items. As you may have seen from other companies in the past few days, COVID-related issues are impeding FDA's ability to conduct pre-approval inspections. In normal course, we believe these CRL requests would have been addressed in the context of a pre-approval inspection. We'll talk a little bit more about that in a minute, but it's important to understand that the CRL did not identify or raise any concerns related to clinical efficacy or safety, and no further clinical studies were requested by FDA to support approval of the application.
We were quite surprised to receive the CRL following a week of active and productive discussions on the label with the Division of Psychiatry. I won't give any specific insight into the label until it's finalized upon approval, but it's important to understand that two different divisions of FDA are involved here. The review conducted by the Division of Psychiatry has gone according to our expectations, including the completion of the successful advisory committee meeting. The CMC review is conducted by a different office within FDA, the Office of Pharmaceutical Quality, or OPQ. In the context of COVID-19, OPQ is conducting only limited pre-approval inspections and is relying instead on document requests. We understand that the CRL was driven by OPQ, as the observations noted in the letter were related to the tablet coating process in certain development batches of ALKS 3831.
We believe that issue has been resolved for some time and that sufficient data are available to address these observations. We've been in contact with the FDA since we've received the CRL, and FDA has indicated that it hopes to work with us expeditiously to review our responses once they receive them. Heather Faulds, who runs our regulatory affairs at Alkermes, can give you a bit more color on this, I'll turn it over to Heather.
Thanks, Rich. Before I provide further detail on the complete response letter, I'd like to provide some additional context around the remote records review process. In normal course, a pre-approval inspection identifies any relevant observations and provides the opportunity for agreement on the provision of additional information or corrective action. However, earlier this year, in light of COVID-19's impact on FDA's ability to conduct inspections, FDA issued a guidance for industry stating that it intends to use other tools and approaches, including remote records requests in lieu of inspections where possible. In circumstances where the records review does not sufficiently support approval, FDA has two primary options to collect additional information. If a pre-approval inspection is required to address FDA's concerns before approval can be granted, the PDUFA date may be extended until such time that the PAI can be completed.
If the agency believes additional documentation may satisfy its concerns, additional information is often requested within the context of a complete response letter. It's important to note that if a question arises during the records review process, the FDA is not obligated to reach out to the sponsor until the action date, even if the sponsor may already have information responsive to FDA's concern. Consistent with guidance, the agency did not conduct a pre-approval inspection at our Wilmington, Ohio, facility during its review of this NDA and instead conducted a remote records review. On September 11th, FDA confirmed receipt of the records requested. Since that date, FDA has not communicated with us about any concerns stemming from this records review, despite our numerous requests for feedback.
The ALKS 3831 complete response letter noted that based on FDA's review of manufacturing records, the agency requires resolution of certain conditions related to the tablet coating process, which had resulted in some eroded tablets in certain development batches of ALKS 3831.
We had identified and addressed this issue and have since manufactured multiple validation batches of ALKS 3831, none of which evidenced tablet erosion. The company believes that it has sufficient data to address FDA's observations and is currently preparing those data for submission. We plan to work expeditiously with the agency to address any remaining outstanding items to support approval of ALKS 3831. With that, I will turn the call back over to Rich.
Thanks, Heather. We can finish up there. I'll just finish by saying I'm confident in our processes and the ability of our team to address these outstanding CMC issues in support of the approval of 3831. We appreciate that this is as frustrating for our shareholders as it is for us. At this point in time, our anticipated launch timing planned for the end of Q1 next year may or may not be impacted. We will provide updates as we progress with FDA. We are quite excited about the opportunity 3831 represents for the patients and the company. We've developed a very clear go-to-market strategy, which leverages our growing presence in this market. You can expect to hear much more about that as we complete the regulatory process. With that, I'll turn the call back over to Sandy to run the Q&A.
Thanks, Rich. Melissa, we'll now open the call for Q&A, please.
Thank you. If you'd like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. In the interest of time, we ask that you each keep to one question and one follow-up. Thank you. Our first question comes from the line of Vamil Divan with Mizuho. Please proceed with your question.
Hi, great. Thanks for taking my question. Maybe just, despite limiting what you can say right now, but just I'll ask a couple questions at least. Just one, in terms of when you think you'll be able to speak to the FDA next and maybe provide a little more insight on the process around the manufacturing review. I'm not sure if there's anything officially scheduled or if there's any sort of general timeline we should expect and when we should hear back. It sounds like when this is resubmitted, ultimately it'll be a Class 1, so I guess a two-month sort of review process and not the six-month review. Can you just confirm if that's a reasonable assumption?
Yes. Hi, this is Heather. Thanks for your question. We've already been in contact with FDA, and we plan to collaborate and work expeditiously with them on the resubmission. Currently, within Alkermes, we are assembling the necessary documentation to address the issue, and we feel confident in that. This is a Class 1 resubmission, as you said. Generally, FDA acts on Class 1 resubmissions within two months.
Okay. Thank you.
Thank you. Our next question comes from the line of Cory Kasimov with JP Morgan. Please proceed with your question.
Hey, good morning. Thanks for taking the question. I guess, it sounds like the whole coding issue is something that you already identified and addressed. Is it really a function-- like, the hard part of this, at least from what the FDA said it so far, is taken care of and it's more the paperwork now. Is that the right way to think about it?
Yeah. Cory, it's Rich. Good morning. Yeah, that's what's so frustrating about it, is that this is an issue that related to development batches. Typically in development, you're working through various manufacturing issues. We had identified this and fixed it. It could have been resolved with a document request in the context of the review, We found out about it in the CRL.
Okay. As we think about potential timing, it sounds like much of this might just come down to whether or not the FDA decides they need to inspect this facility or just the electronic records would be sufficient, right? If they needed to do the inspection, This becomes more a function of COVID and how long it takes them to do it in the midst of the pandemic. Am I thinking about it right?
I'll give you my perspective, but I'll let Heather fill it in. That's right. That's why we're actually encouraged that it came back in the form of CRL as opposed to a delay in just pushing out the PDUFA date pending inspection. We're hopeful that it should be resolvable with documentation, but you never know until it's over. Heather, I'd be happy to hear your point of view on that.
I just wanted to underscore that we are encouraged that we received a CRL rather than a request for pre-approval inspection. We do feel like we have the documentation needed to resolve it, and we can move forward with the Class 1 resubmission swiftly.
Thank you, guys.
Thank you. Our next question comes from the line of Brandon Folkes with Cantor Fitzgerald. Please proceed with your question.
Hi, thanks for taking my question. Maybe can you confirm beyond the erosion if there were any other issues raised in the CRL? Just so that I'm clear on this, the issue has been identified and resolved. The PDUFA was Friday. In terms of documentation, was there anything submitted to the FDA in terms of that resolution prior to the CRL, or was it just that you thought this was just?
Identified as an isolated incident in terms of those batches and look at the totality of manufacturing? Any color to understand, in terms of how the issue's been resolved, given that the CRL has just raised it. Thank you.
There were no other issues identified in the complete response letter. They were largely around the erosion issue. We didn't submit anything prior to the CRL because we didn't know that it was an issue before the CRL. The issue does go back to development batches, as Rich said. The team has resolved the issues, and we successfully executed on our validation batches. As part of the Class 1 resubmission, we'll be including those executed batch records along with the associated documentation.
All right. Thank you.
Thank you. Our next question comes from the line of Umer Raffat with Evercore ISI. Please proceed with your question.
Hi, thank you. Heather, Rich, here's my question. You mentioned there's two primary options FDA had. One was do the PAI, the pre-approval inspection, or just request additional documentation. You said they went with the latter. My understanding was that during COVID, FDA is only doing pre-approval inspections since July on "mission-critical" drug with a huge public health benefit. I wonder to what extent that tied into the lack of pre-approval inspection, or do you think there's additional things about this drug or about this facility that made FDA feel reasonably comfortable they didn't necessarily have to go in personally? Could you just elaborate on that?
Yeah, Umer, good morning. I'll give my point of view, then we'll ask Heather for hers. Yeah, I think it's what you mentioned. The Wilmington facility is an active GMP manufacturing site. We make VIVITROL, ARISTADA, multiple products there for a long time. It's been inspected many times. It had a successful pre-approval inspection in 2018. It's a site that's known to FDA. We expected in the context of COVID to have a remote records review under a provision of the law that's called 704(a)(4), which is the authority by which they conduct these remote records review. We were not surprised not to have a PAI. We weren't surprised to receive the CR on that focused topic. Heather, feel free to chime in on that.
Yeah, I would just underscore what Rich said, add, as we just stated earlier, that during the remote records review process, the agency has no obligation to reach out to the sponsor to ask for additional documentation or information prior to the complete response letter.
Got it. Okay. Got it. Rich, how has the timing not changed? I thought the reason it was end of Q1 launch was because of scheduling time. I got to believe you have to wait till approval before that process starts. I was just curious, the end of Q1 still possible?
No, that's a great question, Umer. Thank you for asking. I should have brought it up proactively. I see, because actually the descheduling process is not driven by 3831 per se. It's driven by samidorphan. Because samidorphan in development, because of its structure, was deemed a Class 2, category 2, during development. FDA has recommended DEA, and DEA has now recommended that samidorphan be descheduled. That descheduling process is still underway, it hasn't been affected by this FDA action. We continue to expect that to be resolved in Q1. When the approval comes for 3831, it will be a descheduled drug.
Thank you very much. Very helpful.
Thank you. Our next question comes from the line of Akash Tewari with Wolfe Research. Please proceed with your question.
Hey, guys. Your PR noted that you had not completed labeling discussions with the FDA on 3831. Would you know at this point if the FDA was going to raise any issues on labeling, let's say if they had issues with the REMS, and do you feel like these separate discussions could further delay approval? In terms of timelines, is it generally normal for labeling discussions to be occurring of the week of the PDUFA? Thank you.
Hi, this is Heather, I can answer that question. We were in active labeling negotiations with FDA through last week. We're happy with where things stand, and we expect that we'll be finalizing the labeling negotiations expeditiously with the agency after we submit our Class 1 resubmission.
Akash, it's Rich. Unfortunately, it's not unusual at all to be in label negotiations right up until the very last moment of the action date.
Okay. Just to be clear, on the issue of whether you're going to have a REMS program related to 3831, you guys currently feel like that will not be a requirement. Is that fair to say?
No, none of our assumptions have changed on that.
Good. Thank you.
Thank you. Our next question comes from the line of Jason Gerberry with Bank of America. Please proceed with your question.
Hi, good morning. Thanks for taking my question. Rich, I just wanted to follow up on the samidorphan part. I feel like we've been talking about the descheduling of samidorphan for two years. What is
I guess, taking so long and the confidence that you'll have it all sort of resolved in the near term. Is it just that you've gotten more concrete FDA guidance as of late as it pertains to the samidorphan descheduling?
Yeah, you're right. Unlike PDUFA, there's not a clock that this happens on. I think that the descheduling of samidorphan, in many ways, was still pending an FDA approval of the drug, or the expectation of FDA approval of the drug. We do know the process works where FDA makes a recommendation to DEA about scheduling or descheduling. Almost, I think, 100% of the time, DEA follows FDA's recommendation. We knew last spring that FDA had recommended DEA to deschedule samidorphan. Then it went into the DEA black hole, and we recently learned that it's come out of the DEA. It's gone to OMB, where they make a determination. It goes back to DEA. We expect it to be published in the Federal Register in short order. None of us know exactly when, but we expect that notification to be published fairly soon.
It's just something that proceeds at its own pace. We are making progress.
Got it. If I could just squeeze a follow-up in. Are you expecting to be able to, it sounds like, submit within weeks or one month, or can you be any more specific how quickly you can turn around and resubmit?
We're going to go as fast as we possibly can. Heather's in charge of the actual operations to do it, so I'll let her provide a little bit more color if she can. The fact is we activated right away, and we're going like hell, and the fact is, we think that this is probably already solved. That's helpful.
Yeah, just to build on that, the team is moving swiftly to put together all the documentation needed for the resubmission. There's not a need to generate new data, so it's just a matter of assembling documentation and getting the submission out the door.
Got it. Great. Thank you.
Thank you. Our next question comes from the line of Terence Flynn with Goldman Sachs. Please proceed with your question.
Hi. Good morning. Thanks for taking the question. I was just wondering if you can talk at all about what's left on the commercial preparation side as you head into next year, and then any perspective on pricing, as I'm assuming most of your discussions with payers have happened. That would be great if you could weigh in there. Thank you.
Morning, Terence. Yeah, I won't comment on pricing now other than it's a very standard approach to think about pricing a new psychiatry product in these markets. Commercial is actually quite exciting, I was hoping that on this call, we'd be talking more about that, had we not gotten a CR. We're quite excited about a couple things. One is that we're integrating a lot of the knowledge and learnings of the last few months under COVID and the advent of telepsychiatry and remote interactions with caregivers and so on into what we think is going to be a very modern, streamlined, and efficient launch plan that leverages our current presence in the market with ARISTADA. You'll hear more about that as we get through the regulatory process and we then prepare for launch.
What we really like is the fact that we have a really fine long-acting injectable antipsychotic, now we think we're going to have a really fine oral as well. The two share features of strong efficacy and excellent patient tolerability. I think those are really important elements in the marketplace.
Thank you. Our next question comes from the line of Douglas Bell with H.C. Wainwright. Please proceed with your question.
Hi. Good morning. Thanks for taking the question. If you could maybe help me understand the chronology a little bit. It sounds like you had, prior to the CRL, identified these issues on your own and corrected them. I'm just curious why you actually didn't reach out to the FDA to inform them that these corrections have been made. Was it just that you didn't think that they would be of sufficient magnitude to warrant the CRL? Then just as a follow-up question on the commercialization and still staying on track. Does that mean that given the news and your confidence in approval, that you're going to proceed with the pre-commercialization activities that you would have done if you had gotten an approval today? Thank you very much.
Okay. I'll start with the second one, and I'll ask Heather to answer the first. Yeah, we're going to continue to proceed per the anticipation for the launch of the drug because we think that's going to happen in Q1, and we want to be ready for that. Heather, you might want to comment on some of the chronology.
Yeah, certainly. In regards to the chronology and identifying issues on our own, we did, and that's part of the normal development process. The issues were identified in development batches, as I mentioned before, and the team addressed the issues and have successfully manufactured a number of batches since then. There was really no need to reach out to FDA because it's just part of normal drug development. Like we said, we were surprised that it was an issue in FDA's mind, and we didn't hear about it or learn about it until the complete response letter.
Just as a follow-up, Heather, it sounds like as part of the NDA, there was data from subsequent batches that had corrected this issue. Is that correct?
Yes. That were not included in the NDA because with small molecules, the validation reports are not included in NDAs.
Okay.
Doug, just to make a finer point on that. In normal course, you have a pre-approval inspection. The pre-approval inspection concludes with a closeout report that either results in some discussion about remedial things that should be done, the issuance of a Form 483 and corrective actions. You have immediate feedback on what needs to be done. Under this new 704(a)(4) provision, they request records, we send records in, then you might not hear anything until the CR. I don't think anybody in the industry thinks that's a good plan, but that's the current plan that's operative under COVID.
Thank you. Ladies and gentlemen, there are no further questions. At this time, I'll turn the floor back to Ms. Coombs for any final comments.
Thank you. Thanks, everyone, for joining us on the call this morning. Please don't hesitate to reach out to us at the company if you have any follow-up questions. We'll make ourselves available. Thank you so much.
Thank you. This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.