[00:00:00] Speaker 00: case number 23-5200, Vanda Pharmaceuticals, Inc., at balance, versus United States Food and Drug Administration, et al. [00:00:09] Speaker 00: Mr. Hughes for the at balance, Mr. Myers for the at police. [00:00:18] Speaker 06: Good morning, Mr. Hughes. [00:00:19] Speaker 06: Whenever you're ready. [00:00:20] Speaker 03: Good morning, Your Honor. [00:00:21] Speaker 03: May it please the court, Paul Hughes, for Appellant Vanda Pharmaceuticals. [00:00:26] Speaker 03: This case turns on a single question of statutory construction. [00:00:30] Speaker 03: Does Fast Track designation focus on the physical properties of the drug? [00:00:36] Speaker 03: That is, whether the evidence the drug may benefit patients with unmet medical needs, or does Fast Track designation turn instead on the status of the sponsor's drug development program? [00:00:47] Speaker 03: The text and manifest purpose of the statute compel the former reading, but FDA instead applies the latter. [00:00:54] Speaker 03: It did so here, and we think that was error. [00:00:57] Speaker 06: Why can't it focus on both? [00:00:59] Speaker 03: Well, we think, Your Honor, that that would both pervert the intent of the statute and also violate the direct terms. [00:01:07] Speaker 03: The way the statute operates is there's first an assessment of the drug's potential, that is, the drug as a molecule. [00:01:14] Speaker 03: Is there evidence that it could meet an unmet need? [00:01:19] Speaker 03: If the answer is yes to that, the purpose of Fast Track is for FDA and the sponsor to work together to facilitate the development program. [00:01:28] Speaker 06: And in the text, Congress very clearly- Sure, but in the current posture, we take as a given that the drug will not be approved unless and until you do animal studies. [00:01:45] Speaker 03: Well, Your Honor, that is, in the complete response letter, there are recommendations about things the company should undertake in order- This is the clinical hold, which you challenged and lost. [00:01:57] Speaker 03: Well, there is a clinical hold. [00:01:59] Speaker 03: Yes, your honor. [00:02:00] Speaker 06: It says no. [00:02:03] Speaker 06: Human studies are necessary to get the approval under the statute. [00:02:09] Speaker 06: The clinical hold says animal studies are necessary to justify human studies and you refuse to do the animal studies. [00:02:18] Speaker 03: Well, your honor, I think that's inaccurate in a couple of respects. [00:02:21] Speaker 03: So first, to begin with, and I think this is a bit of a merits issue that's not directly before the court, but the legal landscape from when the clinical hold issued to where we stand today has shifted pretty profoundly. [00:02:33] Speaker 03: And that's with the FDA Modernization Act 2.0, because at the time of the earlier litigation about the clinical hold, there was, as the district court judge found at that time, [00:02:44] Speaker 03: statutory language suggesting that animal studies may be required in essentially all cases. [00:02:50] Speaker 03: There's now a pretty profoundly different statutory structure against which FDA operates that Congress very clearly said we need to move away from mandatory animal testing in all cases and have a much more specific analysis [00:03:05] Speaker 03: as to what sorts of toxicity studies work in any given case. [00:03:10] Speaker 03: Now, again, I don't think that issue is before the court directly. [00:03:14] Speaker 03: My friends try to suggest that we're challenging somehow, collaterally, the partial clinical hold. [00:03:17] Speaker 03: And let me assure you, we are not. [00:03:20] Speaker 05: Certainly the way it comes across. [00:03:22] Speaker 03: That we're challenging the partial clinical hold? [00:03:24] Speaker 05: Absolutely. [00:03:25] Speaker 05: How could you not read these reviews and not think that was an issue? [00:03:29] Speaker 05: Greg, you should finish up. [00:03:31] Speaker 06: I'm just sorry. [00:03:32] Speaker 06: Just, um, just help me understand. [00:03:36] Speaker 06: You're saying there's been an intervening statutes since the clinical hold was put in place. [00:03:43] Speaker 03: Yes, your question. [00:03:45] Speaker 03: The FDA Modernization Act 2.0. [00:03:48] Speaker 03: And this is why, though, just to get to the focus of the case, the fast track program [00:03:55] Speaker 03: It's designed to facilitate enhanced conversations between a sponsor and FDA over development programs, especially those that are troubled. [00:04:04] Speaker 03: It's for FDA and sponsors to work together because there's a molecule that as its physical properties has promise, but is not reaching the hands of the American public where it can do good. [00:04:15] Speaker 03: That's the point of the program. [00:04:18] Speaker 05: The agency says this should occur at the IND stage, not once you submitted an application. [00:04:24] Speaker 05: Why is that wrong? [00:04:25] Speaker 03: Well, you know, I think the agency is quite clear that fast track can be approved anytime up until marketing approval. [00:04:32] Speaker 03: That's, I think, pretty plainly in the materials. [00:04:35] Speaker 03: I want to say it's joint appendix page 691. [00:04:39] Speaker 03: And here in the complete response letter, if the court looks that they submitted under 28J at page nine, for example, there's a whole list of recommendations that FDA has [00:04:52] Speaker 03: for the sponsor and suggests the sorts of studies. [00:04:55] Speaker 03: The whole purpose of Fast Track would be to facilitate, to enable those conversations between FDA and Vanda to occur to help those studies. [00:05:04] Speaker 05: Let me make sure I understand. [00:05:06] Speaker 05: The only issue that's before us based on what you've presented is FDA's denial of Fast Track designation. [00:05:14] Speaker 05: Yes, Your Honor. [00:05:15] Speaker 05: Parties have gotten off into a lot of collateral issues. [00:05:18] Speaker 05: That's the only issue. [00:05:19] Speaker 05: Your Honor. [00:05:19] Speaker 05: The agency, let me just tell you my concerns, please. [00:05:22] Speaker 05: The agency says there is no point to fast track. [00:05:28] Speaker 05: That's where we're at now. [00:05:29] Speaker 05: Because that should, if it's going to occur, it occurs at the IND stage. [00:05:34] Speaker 05: You file an application and they make a compelling argument. [00:05:37] Speaker 05: There are other ways to expedite consideration once you file an application. [00:05:42] Speaker 05: But fast track makes no sense. [00:05:44] Speaker 05: So the first question I have is, why are they wrong on that? [00:05:47] Speaker 05: And if they are right, that's the end of it as far as we're concerned. [00:05:51] Speaker 05: The case is over because the only issue is whether you were improperly denied fast track consideration. [00:05:57] Speaker 05: The other thing I'd like for you to answer for me, if you would please, what do you think you're going to get if you win on that issue? [00:06:09] Speaker 05: that you haven't already gotten, or that is like, what's the remedy? [00:06:15] Speaker 05: The only issue before us is whether you were improperly denied fast-track designation. [00:06:22] Speaker 05: That's the only thing that we should be considering. [00:06:25] Speaker 05: And let's say you win on that. [00:06:27] Speaker 05: You were improperly denied, and the agency is wrong. [00:06:30] Speaker 05: It doesn't have to be at the IND stage. [00:06:33] Speaker 05: It can be at any stage. [00:06:34] Speaker 05: Let's assume they're wrong, and you're right. [00:06:37] Speaker 05: What would we order happen? [00:06:38] Speaker 03: Okay, very, very, very important three questions. [00:06:42] Speaker 03: If I could take that in three parts, the first is the premise of what we're asking for, which I think is important. [00:06:46] Speaker 03: The second is, is there still a live controversy now that we're in the NDA stage and not at the IND stage? [00:06:51] Speaker 03: And the third is, if we're right about that, what do we get? [00:06:54] Speaker 03: What happens? [00:06:55] Speaker 05: Is that? [00:06:55] Speaker 05: I don't want you to think I want to wander into the model of muteness. [00:07:00] Speaker 05: I understand all of those arguments. [00:07:02] Speaker 05: I'm asking you a more specific, direct question. [00:07:06] Speaker 05: If you win, what do you think you'll get? [00:07:08] Speaker 03: Yes, OK. [00:07:09] Speaker 03: So to begin with the premise, I agree with your honor of the premise. [00:07:12] Speaker 03: There's one question here. [00:07:14] Speaker 03: Was fast track rightly or wrongly denied? [00:07:16] Speaker 03: And we think that essentially turns on one question, which is the statutory interpretation issue we've put forward. [00:07:20] Speaker 03: So I agree with your honor on the premise. [00:07:23] Speaker 03: To jump to the court's last question about what is it that we get, we get two things that the statute provides us. [00:07:30] Speaker 03: One, facilitation of the development program, and two, expedition. [00:07:33] Speaker 03: And this is really critically important at this very juncture where this development program lies. [00:07:39] Speaker 03: With the complete response letter, there are essentially two things that the company can do at this point. [00:07:45] Speaker 03: And again, the complete response letter came last week, but the regulatory structure gives, well, there are three options. [00:07:51] Speaker 03: They can withdraw entirely and be done. [00:07:53] Speaker 03: I can assure you that's, I don't think, occurring. [00:07:55] Speaker 03: The second is a resubmission. [00:07:57] Speaker 03: That is, go do more studies that FDA has laid out in the complete response letter. [00:08:03] Speaker 03: Or third, proceed with the process. [00:08:06] Speaker 03: And as this court in Nostrum Pharmaceuticals two years ago say, [00:08:09] Speaker 03: attempt to convince senior leadership at FDA that the complete response letter is wrong. [00:08:14] Speaker 03: So I want to talk about those two branches, because those are the two things that could occur from now. [00:08:19] Speaker 03: If the company were to choose to engage in more studies and go down the resubmission pathway, we are precisely at the point of fast track, which is having conversations with not just low level folks, but more senior officials at FDA to say, here's how you can design these studies. [00:08:37] Speaker 03: Here's what you need to do. [00:08:38] Speaker 03: and can listen to our concerns about how actually enrolling the number of patients that they suggest need to be enrolled is essentially impossible. [00:08:46] Speaker 05: So you're talking about in light of the agency's current concerns, there would be opportunities for expeditions. [00:08:55] Speaker 05: Yes, Your Honor. [00:08:55] Speaker 05: The challenge before us is the agency's past responses on fast track. [00:09:01] Speaker 03: But if this drug is designated as Fast Track, that would stay with the drug unless and until the agency at some point remove that designation. [00:09:11] Speaker 03: And so a designation of Fast Track would have very significant consequences at this moment as the agency, as Vanda wants to go to the agency and says, we need to talk about this because we have serious concerns about things you've said. [00:09:25] Speaker 03: We want to have a meaningful scientific conversation with the agency. [00:09:30] Speaker 03: That's what Fast Track allows pharmaceutical sponsors to be able to do in a meaningful way. [00:09:35] Speaker 03: That's what the company wants and needs. [00:09:37] Speaker 03: So having Fast Track. [00:09:39] Speaker 05: As my colleague has already mentioned, the case is at a different posture now. [00:09:43] Speaker 05: And they've confirmed the position about what you're missing. [00:09:46] Speaker 05: And you continue to balk at their clinical holding, which you not battled. [00:09:54] Speaker 05: What's to expedite? [00:09:57] Speaker 05: If you're not willing to pursue the studies that the agency has said that you must pursue, I assume you can continue to challenge the agency's rulings within and see what happens. [00:10:11] Speaker 05: But if you're not willing to do any accommodation on the clinical hold, you let that go. [00:10:16] Speaker 05: And they've said that's critical, and you're not prepared to move [00:10:21] Speaker 05: What's the fast track? [00:10:22] Speaker 03: Well, Your Honor, first, I don't think the company has taken or stated any public position about the complete response letter in the six days or so since it was issued. [00:10:30] Speaker 03: No, no, I totally understand. [00:10:31] Speaker 05: But you have taken a position on the clinical hold. [00:10:34] Speaker 05: And you said you're not going to do that. [00:10:35] Speaker 05: Well, Your Honor, you view the case differently. [00:10:39] Speaker 03: Your Honor, I don't think the company has said anything. [00:10:41] Speaker 03: And I couldn't tell. [00:10:41] Speaker 03: You didn't pursue an appeal. [00:10:43] Speaker 03: Yes, your honor. [00:10:46] Speaker 03: But in terms of what it is the company is going to do at this moment in response to a complete response letter that came out was it five, six days ago, the company has not made any public statements or committed one direction. [00:10:59] Speaker 05: That's why I'm not understanding what is it we would order happen. [00:11:02] Speaker 03: All we want is fast-track status. [00:11:05] Speaker 05: Why would we give you that when you have not satisfied their disposition on the clinical hold? [00:11:11] Speaker 05: Why would this court say, yeah, you're entitled, assuming they're wrong on when [00:11:16] Speaker 05: fast track occurs, IND or after you file an application. [00:11:20] Speaker 05: Let's assume their position is incorrect and you're right, you can get fast track at any time. [00:11:24] Speaker 05: Let's assume that's right. [00:11:25] Speaker 05: I don't understand what we would give you. [00:11:27] Speaker 03: Well, Your Honor, and I want to be clear about this. [00:11:29] Speaker 03: This goes to our fundamental disagreement on the statutory construction. [00:11:32] Speaker 03: We do not believe that a clinical hold is a valid basis standing alone to deny fast track status. [00:11:39] Speaker 02: Have the FDA ever granted fast track status after a clinical hold? [00:11:43] Speaker 03: You know, I don't have the full universe of FDA decisions. [00:11:46] Speaker 03: That may be a question for my colleague. [00:11:48] Speaker 03: So I don't have particular insight as to that. [00:11:52] Speaker 02: The reason I ask that question is because Judge Edwards is referring to what you have not done in compliance with the follow-up letter or recommendations. [00:12:03] Speaker 02: But I wanted to know just generally if FDA has ever done that, because if they've never granted fast-track status based on a clinical hold, then is that a different matter than you not complying? [00:12:14] Speaker 03: Well, what we have put into the record is, I think, roughly six or so prior fast-track determinations. [00:12:21] Speaker 03: And in every case, they use the same worksheet. [00:12:24] Speaker 03: And the worksheet asks, is there a clinical hold? [00:12:27] Speaker 03: And if the answer to that is yes, the instructions say fast-track shall be denied. [00:12:31] Speaker 03: And our submission here, and this takes us to the central legal issue of the case, is that is a legal error. [00:12:37] Speaker 03: And the reason behind that is because FDA is focusing on the drug development program and not the molecule. [00:12:45] Speaker 06: We'll get to the legal error before you sit down. [00:12:49] Speaker 06: But I think what we're all probing one way or another is, why does it matter? [00:12:55] Speaker 06: Well, as I said, the document. [00:12:58] Speaker 05: There's something here that you folks in the business [00:13:02] Speaker 05: may have in the back of your minds. [00:13:03] Speaker 05: That seems terribly important to you. [00:13:05] Speaker 05: It certainly doesn't leap out on the pages. [00:13:07] Speaker 03: So again, let me just start again on the importance moving forward. [00:13:13] Speaker 03: Because as I said, there are two branches we could take. [00:13:16] Speaker 03: We could, as Nostrum Pharmaceuticals explains, try to convince senior FDA leadership that we are, in fact, correct in the submission as it now stands. [00:13:25] Speaker 03: That's option one. [00:13:26] Speaker 03: Option two is we could do the resubmission process, which is we do additional work, and then we come back to FDA. [00:13:35] Speaker 03: In either of those two scenarios, fast-track matters quite a good deal, and I'd be happy to explain why that is for both of those. [00:13:42] Speaker 06: Let me ask you this. [00:13:43] Speaker 06: If you get fast-track status, will you commit to doing animal studies? [00:13:51] Speaker 03: You know, Your Honor, that's a question I don't have authority to answer. [00:13:54] Speaker 03: I don't know the answer to that question. [00:13:55] Speaker 06: I mean, unless you answer that, unless either you say yes to that question or unless this recent order that just came out undid the clinical hold, which I don't think it did, but it just doesn't matter. [00:14:11] Speaker 03: You know, that again, we can say on mootness for a second, we can go to the merits. [00:14:15] Speaker 03: Our fundamental merits position is that is a wrong way to think about what when fast track is available. [00:14:20] Speaker 03: I'll spot you then. [00:14:21] Speaker 06: So let's say you were absolutely entitled to fast track status and all the benefits come with it. [00:14:29] Speaker 06: That wouldn't have barred FDA from saying, given where we are now, you need to do animal studies. [00:14:38] Speaker 03: Working with FDA, I mean, that suggests that there is an absolute and that there can't be an agreement between the parties, either because Vanda changes its position or FDA changes its position. [00:14:49] Speaker 03: And again, I know you've asked about Vanda changing its position, and that is, of course, something that the company always has the right to do. [00:14:54] Speaker 03: But it's also critically important to recognize, as I said earlier, the law has changed since the clinical hold came into place because Congress has said the mass killing of dogs for a pharmaceutical study isn't always justified. [00:15:06] Speaker 03: And you have to do a case-specific analysis [00:15:08] Speaker 03: And you have to look at new technology that exists now that didn't exist decades ago to see is the benefit of mass destruction of animal life justified in any particular case. [00:15:19] Speaker 02: But isn't it up to the FDA to consider what alternatives it would want? [00:15:23] Speaker 02: It's not something that you all get to require of the FDA. [00:15:26] Speaker 03: No, I think it's specific to each case. [00:15:30] Speaker 03: And what we want is to have a conversation with FDA to actually sit down and talk about the science and say, what about these alternative models that FDA Modernization Act 2.0 specifically requires the agency to consider? [00:15:44] Speaker 03: In our view, the agency has never given us an answer as to why those alternative models are insufficient here. [00:15:50] Speaker 03: Fast Track would have the facilitation where we could have those scientific conversations. [00:15:55] Speaker 03: And maybe FDA could convince Vanda. [00:15:58] Speaker 03: Maybe Vanda could convince FDA. [00:16:00] Speaker 03: The point is we don't know the outcome of that facilitation of those meaningful high-level conversations until they occur. [00:16:06] Speaker 05: And you've never had conversations with the agency officials [00:16:10] Speaker 03: You know, we've had the bare minimum of the regulations mandate. [00:16:14] Speaker 05: Your concerns about the clinical hall questions have never been discussed with agency officials. [00:16:20] Speaker 05: That's not the way I read the record. [00:16:21] Speaker 03: Well, Your Honor, I've been party to most of those calls and I can tell you most of the time we have [00:16:25] Speaker 03: very junior FDA officials who come and tell us those are regulatory questions that they cannot answer and will not discuss with us. [00:16:32] Speaker 03: And so we do not have meaningful conversations with anyone at the agency to actually engage on these issues. [00:16:39] Speaker 03: We think Fast Track would change that. [00:16:44] Speaker 05: I know you're frustrated because you don't think we understand your world. [00:16:47] Speaker 05: We're frustrated because you appear not to understand our world. [00:16:51] Speaker 05: What would our orders say? [00:16:52] Speaker 05: OK, they win. [00:16:55] Speaker 05: Now go back and talk. [00:16:57] Speaker 05: That's what we would say. [00:16:58] Speaker 05: And talk fast. [00:16:58] Speaker 05: Your honor, I want something less than that even. [00:17:01] Speaker 03: What I want is the court to find that the denial of Fast Track, that is a specific agency action that's before you, was premised on a legal error. [00:17:09] Speaker 03: That is all the court needs to find. [00:17:11] Speaker 03: And then this goes back to FDA. [00:17:12] Speaker 03: That's the one ask I have of you, which is a very straightforward ask under the EPA. [00:17:16] Speaker 05: Can we possibly say [00:17:18] Speaker 05: with any assurance that the denial of Fast Track was wrong, assuming you can get it once the application has been filed, assume the agency's wrong or not. [00:17:26] Speaker 05: How can we say it's wrong? [00:17:27] Speaker 05: When the clinical hold question looks to be a rather strong problem for you, a weighty problem against your position. [00:17:35] Speaker 05: That is, you have refused to change your position and the agency, at least at first blush, appears to reasonably say, no, with the clinical hold problem as it is, [00:17:46] Speaker 05: That's it. [00:17:48] Speaker 05: There's nowhere to go. [00:17:49] Speaker 05: You've refused to move. [00:17:51] Speaker 05: And so the agency says, here we are. [00:17:53] Speaker 03: Well, Your Honor, this is why I think my request is much less than the court thinks that I'm asking of it. [00:17:58] Speaker 03: All we want is a set aside of a denial. [00:18:01] Speaker 03: We are not asking the court to compel the grants. [00:18:05] Speaker 03: What we say is we want a set aside of an order that was based on a legal flaw. [00:18:10] Speaker 03: And let's be clear about this. [00:18:11] Speaker 03: There are a lot of new facts that have occurred in the last two and a half years since fast track denial occurred. [00:18:17] Speaker 03: We're not saying the court needs to look at all of those intervening facts in two and a half years and dictate to FDA what the conclusion is. [00:18:25] Speaker 03: What we want is APA set aside relief under 7062, where then you say this was based on a legal error. [00:18:31] Speaker 03: Here's what the statute, the proper framework [00:18:33] Speaker 03: send it back FDA work with vanda and then we'll come to the legal error is what is the quality what is the what does the statute focus on for making the determination as to whether or not a drug qualifies as a fast track product our position just to crystallize this legal error [00:18:52] Speaker 03: is the statute is focused on what evidence about the physical properties of the drug is put forward. [00:18:58] Speaker 03: FDA's position is they can look at the entire development program and if they think there is a problem with the development program, deny on that basis. [00:19:06] Speaker 03: Our fundamental submission is that puts the cart before the horse because the purpose of the Fast Track program is to actually work with troubled drug development programs and help bring those products to the market. [00:19:19] Speaker 05: that it demonstrates potential to address unmet medical needs. [00:19:23] Speaker 05: And the agency's position, at least on paper, looks like a perfectly reasonable response in light of your resistance with respect to the clinical hold. [00:19:35] Speaker 05: I mean, you haven't shown [00:19:37] Speaker 05: at least as far as I can see, that this will address unmet medical needs. [00:19:43] Speaker 05: So that's what you want the disposition to hinge on? [00:19:46] Speaker 03: And your honor, this is exactly where the legal dispute between me and my friend occurs is because their view is this focuses on a review of the regulatory development program. [00:19:57] Speaker 03: Our view is this actually looks at what do we know? [00:20:00] Speaker 03: What are the physical properties of this drug? [00:20:02] Speaker 03: And there are a few reasons I think our interpretation is the correct one. [00:20:05] Speaker 03: First is in this statute, 356, Congress routinely distinguished between the term drug and the term development program. [00:20:14] Speaker 03: Congress knew that these are different things and it used these terms with precision. [00:20:19] Speaker 03: It says, does the drug have potential? [00:20:21] Speaker 03: And when we step back, this is what makes sense. [00:20:24] Speaker 06: The word potential, it seems like it's the key keyword in the statute, right? [00:20:31] Speaker 06: Are you a hockey fan? [00:20:35] Speaker 06: Let me give you a hypothetical. [00:20:37] Speaker 06: I hope this is helpful. [00:20:39] Speaker 06: Suppose I say, does Alex Ovechkin have the potential to break Wayne Gretzky's record? [00:20:50] Speaker 06: Really famous hockey record. [00:20:53] Speaker 06: He's very late in his career. [00:20:55] Speaker 06: He's very close to the record. [00:20:59] Speaker 06: I'm not clear whether he'll get there, right? [00:21:02] Speaker 06: Most people would say, yeah, he has the potential, right? [00:21:07] Speaker 06: So suppose I'll take it. [00:21:09] Speaker 06: Take that as take that as again, except the premise. [00:21:13] Speaker 06: Suppose the NHL now suspends him for five years. [00:21:18] Speaker 06: And you know, five years from now he's just too. [00:21:21] Speaker 06: He's going to be too old to play. [00:21:25] Speaker 06: If you ask me, does he have the potential? [00:21:29] Speaker 06: to break the record. [00:21:32] Speaker 06: Nothing about him has changed, but there's just an intervening legal rule that makes it impossible he will ever get there. [00:21:39] Speaker 06: I would say no, he doesn't. [00:21:42] Speaker 06: He can't get to the end point. [00:21:46] Speaker 06: And this situation feels more like that. [00:21:49] Speaker 03: But the question is, potential is a very important word. [00:21:53] Speaker 03: But the question is, what is it that has potential? [00:21:56] Speaker 03: And what the statute says is, does the drug have potential, not the current drug development program have potential? [00:22:03] Speaker 03: And this is an important distinction, because the drug is an immutable thing. [00:22:07] Speaker 03: Either it works in particular conditions or it doesn't. [00:22:10] Speaker 03: And what we're trying to do is gather the evidence to make a determination. [00:22:13] Speaker 06: It will not and cannot cure unmet medical needs [00:22:19] Speaker 06: Unless and until it's approved. [00:22:21] Speaker 03: Unless and until it's approved. [00:22:23] Speaker 03: But that's the purpose of Fast Track is to say if there is a resolvable obstacle between the pathway of where we are today and where we can get to get a valuable drug in the hands of American patients, the purpose of Fast Track is to work with the agency to see if those obstacles can be removed. [00:22:39] Speaker 03: So to your question, if there is a physical possibility, can a suspension be lifted? [00:22:44] Speaker 03: Perhaps. [00:22:44] Speaker 03: The question is, what are we looking at? [00:22:46] Speaker 03: Are we looking at, you know, the drug as the physical thing? [00:22:50] Speaker 03: Are we looking at the development program as it exists as a regulatory matter? [00:22:55] Speaker 03: Congress chose to use the words drug and potential. [00:22:57] Speaker 02: And again, because the purpose of this program is to fix troubled development programs, not to- You could define this by, are you going after long-term or short-term because you're quibbling with that too. [00:23:08] Speaker 03: And let me be very clear about that because I think that was murky in the briefs and probably we could have done a better job clarifying that. [00:23:14] Speaker 03: My secondary fallback argument, it is not my principle argument between long term and short term. [00:23:19] Speaker 03: My principle argument is FDA applied the wrong legal standard. [00:23:24] Speaker 03: And if we're right about that, we think that's all the court needs to decide. [00:23:28] Speaker 03: If you disagree with me in that principle submission, we also think that their analysis of the drug development program was wrong because they focused on long-term rather than short-term. [00:23:37] Speaker 02: But I want to be clear, these are two- You're saying what they did. [00:23:40] Speaker 02: I'm asking you a direct question about what is your position with respect to are you applying for long-term versus short-term? [00:23:48] Speaker 03: In terms of the the application, yeah, the fast track application. [00:23:52] Speaker 03: Yes, the fast track application. [00:23:53] Speaker 03: Your honor was it. [00:23:55] Speaker 03: It did not specify a duration of treatment. [00:23:58] Speaker 02: It said you were looking for pursuing assistance with chronic. [00:24:05] Speaker 03: Of conditions we were looking for assistance with symptoms of gastroparesis broadly and we didn't have a durational limit in part because [00:24:15] Speaker 03: The breakthrough therapy recommendation, the decision that we cite throughout the briefs, this was the letter signed by Dr. Bytes, specifically advised us to look at gastroparesis, including particularly for a short-term indication. [00:24:29] Speaker 03: That was, let me make sure I get a record of this site for the court. [00:24:36] Speaker 03: This is at page 657 of the joint appendix, where FDA says it sees, quote unquote, a potential therapeutic role for [00:24:44] Speaker 03: particularly for short-term relief of nausea in gastroparesis patients. [00:24:49] Speaker 05: Short-term need is not an unmet medical need. [00:24:53] Speaker 05: Sorry? [00:24:53] Speaker 05: It's not an unmet medical need, short-term. [00:24:56] Speaker 03: And let me be clear. [00:24:57] Speaker 03: I disagree with that, but I don't think you can disagree with me on that and still think that we win our principal argument. [00:25:03] Speaker 05: I'm just looking at the record. [00:25:04] Speaker 05: The record doesn't support any assertion to that effect, as far as I can see. [00:25:08] Speaker 05: Short-term, that's where you're bogging down, it seems to me, when you [00:25:13] Speaker 05: You're ignoring what my colleague's asking about the long term. [00:25:16] Speaker 05: Again, I think we're seeing the record the same way. [00:25:18] Speaker 05: The agency was essentially saying, and it explains the clinical hold, the need is long term. [00:25:24] Speaker 05: And you're not willing to do the tests that will show us that there's something really here. [00:25:30] Speaker 05: And so here we are. [00:25:31] Speaker 05: Now, what's the talk about? [00:25:34] Speaker 03: Be clear, your honor, even if the court disagrees with me on the long term short term issue, that doesn't say anything about our principle argument about the legal standard. [00:25:41] Speaker 03: So I just want to be clear what I need to win and what I don't need to win so we can separate those. [00:25:46] Speaker 05: Well, the long and short term have a lot to say about unmet medical needs, which is the statutory standard. [00:25:53] Speaker 05: Our point is that saying, as I understand it, you're not showing anything on the short term or if you want to work in the short term, fine. [00:25:59] Speaker 05: But on the long term, there's some serious work to be done. [00:26:03] Speaker 05: And that's where this potential medical needs. [00:26:06] Speaker 03: So let me respond to this in a few different ways. [00:26:08] Speaker 03: I'll get to them. [00:26:09] Speaker 03: I'll start with the merits between the short term and the long term. [00:26:11] Speaker 03: And then I'd like to try to explain why I also don't think if you disagree with me on that, that is in any way adverse to my position as a whole. [00:26:19] Speaker 03: So on the question of a short-term versus long-term need, to begin with, there is no therapy for idiopathic gastroparesis whatsoever. [00:26:27] Speaker 03: So when we exist in a world in which there is no therapy for a pretty important critical condition, a short-term therapy does have, does meet, by definition, an unmet medical need. [00:26:37] Speaker 03: And this is important because the only drug approved in this space, Reglan, is a drug that FDA approved for diabetic gastroparesis, but it is a short-term indication drug. [00:26:47] Speaker 02: And the point that I just... My problem is that when you're submitting your application, you as the movement of that application should be more specific because that's the one when FDA is reviewing it, they're looking at how you're presenting it. [00:27:03] Speaker 02: Short-term shouldn't be like a fallback position. [00:27:06] Speaker 02: You're going one route or the other, and that's how they're evaluating the application with respect to them requesting these clinical studies. [00:27:12] Speaker 03: About the precise indication, this is where we talk in our briefs, and I think FDA [00:27:17] Speaker 03: agrees with us as a broad matter, indications are iterative in the process in the give and take between an agency and the drug sponsor indications change all the time. [00:27:27] Speaker 03: So you generally start with a broader indication and then you work with FDA in saying, okay, maybe this is too broad, but the evidence is a little bit more tailored in this direction. [00:27:36] Speaker 03: So proposing an indication that doesn't have a durational limit on it, but with the view of that's part of the give and take of an agency, I think is an appropriate place to be. [00:27:44] Speaker 02: But then under the short term, as Judge Edwards was mentioning, you've already got a drug that's out there that's going to be assistive. [00:27:52] Speaker 02: So then that doesn't help. [00:27:53] Speaker 03: Well, for short term, it's only approved for their two branches of gastroparesis, idiopathic, and diabetic. [00:28:00] Speaker 03: It's only approved for the diabetic. [00:28:02] Speaker 03: And second, it's a very unsafe drug. [00:28:04] Speaker 03: It has the highest level of FDA rating of a black box warning saying, if you take this drug, it has very serious side effects. [00:28:11] Speaker 03: And again, let me just read what FDA itself said about short-term. [00:28:14] Speaker 03: I mentioned this a minute ago. [00:28:16] Speaker 03: It's at Joint Appendix 657. [00:28:19] Speaker 03: FDA says it sees, quote unquote, a potential therapeutic role for tridipidin, particularly for the short-term relief of nausea in gastroparesis patients. [00:28:27] Speaker 03: Given FDA has told us that there's a role in short-term relief, I think it's challenging for them to say that short-term, there's categorically no unmet need in that scenario. [00:28:40] Speaker 02: But was that comment to be taken that you should have follow up that you should further supplement your application in that regard. [00:28:48] Speaker 02: Can we look at it as them trying to help you out to say that there might be some possibility that you get approved, but you have more work to do. [00:28:55] Speaker 03: Yes, sir. [00:28:55] Speaker 03: I don't disagree with that. [00:28:56] Speaker 03: The point is the pathway they're suggesting is looking at it as a short term indication. [00:29:02] Speaker 03: And I just say that to respond to the court's point, the challenge of there is no short-term need here. [00:29:07] Speaker 03: We disagree with that. [00:29:09] Speaker 03: But to come back where I started. [00:29:10] Speaker 05: But you didn't want to focus on short-term. [00:29:13] Speaker 03: Your Honor, we want to focus on gastroparesis. [00:29:15] Speaker 03: And we want to work with FDA for whatever they would give us. [00:29:18] Speaker 05: They expect a long-term. [00:29:19] Speaker 05: There's work to be done. [00:29:20] Speaker 05: They told you to focus on short-term. [00:29:21] Speaker 05: You didn't want to. [00:29:23] Speaker 03: Your Honor, we focused on gastroparesis as a whole with the view of we want to work with what FDA- Short-term, long-term. [00:29:29] Speaker 05: You did not want to be pushed to focus on short-term. [00:29:32] Speaker 03: You know, I think that suggests that this nature is some adversarial process between us and FDA, where the real nature is, and this is why we want Fast Track, it's supposed to be collaborative, where we say, we're trying to study gastroparesis, we're trying to get a drug that's going to help gastroparesis patients, let's work together to figure out where this evidence leads and what becomes approvable. [00:29:52] Speaker 03: That is, again, I think goes to why Fast Track is critical. [00:29:57] Speaker 03: But the court can disagree with me on the long-term, short-term, [00:30:00] Speaker 03: and still agree that the fundamental legal issue that we've talked about is all we need in order to win that the fast track denial was unlawful and should be set aside. [00:30:12] Speaker 06: Okay, we'll give you a rebuttal. [00:30:14] Speaker 06: Thank you. [00:30:30] Speaker 04: Good morning, Your Honors. [00:30:34] Speaker 04: May it please the court, Stephen Myers on behalf of FDA. [00:30:37] Speaker 04: I have a lot to say about the merits, but before I get there, I want to start by talking about moodness because this case has really been entirely taken over by events. [00:30:47] Speaker 04: When we filed our brief in February, we explained that Vanda had already submitted a new drug application and thereby gotten all of the benefits to which it might have been entitled for my fast track designation. [00:30:59] Speaker 04: In other words, the point of fast-tracked was to facilitate the submission of the application. [00:31:04] Speaker 04: As we explained in our letter last week, FDA has now completed its initial review of that application by issuing a complete response letter. [00:31:12] Speaker 04: It's not a final order. [00:31:14] Speaker 04: It's not a final order. [00:31:15] Speaker 04: That is correct, Your Honor. [00:31:17] Speaker 04: And so the ball is now in Vanda's court to decide. [00:31:20] Speaker 05: Let me ask you, underlying this argument, I'm sorry to interrupt you, but I don't have this question answered because I'm curious. [00:31:26] Speaker 05: Your argument, the initial argument that I'm seeing between the parties as I read this stuff is you're saying if you can request fast track, it can only be requested during the IND period. [00:31:38] Speaker 05: They're saying that's not true. [00:31:40] Speaker 05: Even if we file an application, we can still seek it. [00:31:43] Speaker 05: What's your statutory support? [00:31:46] Speaker 05: You may have a guidance that says that. [00:31:48] Speaker 05: What's the statutory support for that position? [00:31:50] Speaker 05: Because it seems to me it's critically important that we have that strength, because that's critical to your argument, including your mootness argument. [00:32:00] Speaker 04: So I want to be clear about what our argument is in terms of what the effects are and what the benefits are of a fast strike. [00:32:07] Speaker 05: No, that's not my question. [00:32:09] Speaker 05: My question is, what is your statutory support [00:32:14] Speaker 05: or the position that an applicant can only seek fast track at the IND stage, not once an application has been filed. [00:32:24] Speaker 05: So the statutory side is 356B. [00:32:26] Speaker 04: I know. [00:32:28] Speaker 04: And you think that's support of your position? [00:32:30] Speaker 04: So again, I just want to be clear on what the position is I'm trying to articulate. [00:32:32] Speaker 04: And it's really not about when a fast track application can be filed. [00:32:36] Speaker 04: It's about what you get from fast track. [00:32:38] Speaker 04: And all of those benefits pertain to the developments of a drug. [00:32:43] Speaker 04: Once an NDA is submitted. [00:32:44] Speaker 05: Let me ask, can we clear that table so there is no such argument? [00:32:48] Speaker 05: They can raise the fast-track question at any time they want. [00:32:52] Speaker 05: Is that right? [00:32:52] Speaker 05: You're not conceding that. [00:32:54] Speaker 05: Because that's not what the briefs say. [00:32:56] Speaker 05: So let me make sure I have that straight. [00:32:58] Speaker 05: Right. [00:32:58] Speaker 05: Anytime. [00:32:59] Speaker 04: So candidly, I am not exactly sure when you can request FastTrack. [00:33:05] Speaker 04: But it doesn't really make any sense to think about it. [00:33:07] Speaker 04: Because the benefits of FastTrack, again, all pertain to things that happen while you are developing the drug. [00:33:13] Speaker 04: And then there's the possibility of rolling review. [00:33:18] Speaker 05: Maybe I'm looking at it. [00:33:19] Speaker 05: The way I look at it as a judge and read your argument, your argument clearly suggests that that's what your position is, that they can't advance it beyond. [00:33:27] Speaker 05: Now you support it by saying, and this makes sense because there's no advantage to doing it. [00:33:33] Speaker 05: Later on you're saying once the application is filed. [00:33:36] Speaker 04: There's no advantage So the stack certainly can't trust and certainly once an application has but I don't see the statute saying that and you're not supporting it Again, your honor. [00:33:44] Speaker 04: I'm pointing to 356 be one and and be three which I think are the key provisions But I just I want to take a step back here and emphasize That once there has been a complete response letter again The ball is in Vanda's court to decide where to go from there. [00:33:58] Speaker 05: Here's here's a simple [00:34:00] Speaker 05: to that, I think, if I understand the law correctly, capable of repetition yet evading review is a simple response to your most current mootness argument. [00:34:10] Speaker 05: I mean, it was there before. [00:34:11] Speaker 05: It's certainly here now. [00:34:13] Speaker 05: You say, well, but we've done something, which is not a final order. [00:34:16] Speaker 05: And I'm saying, yeah, but if they really want to push moot, and this is capable of repetition yet evading review, because they're going to come back and say, see what happens? [00:34:24] Speaker 05: This moves too fast. [00:34:25] Speaker 05: They think we can only ask at the IND stage, and we'll never be able to get this resolved. [00:34:30] Speaker 05: We think there's a legal issue to be resolved now. [00:34:33] Speaker 05: And even more so, because they're telling us to come back [00:34:36] Speaker 05: and start again and start doing some new things. [00:34:39] Speaker 05: Their fast-track argument has heft now. [00:34:41] Speaker 05: They're saying we want it done on fast track. [00:34:43] Speaker 05: So there's a legal question we have to decide. [00:34:45] Speaker 04: So a couple of points there, Your Honor. [00:34:47] Speaker 04: First is that, as my colleague said, Vanda has not committed to any direction at this point in response to the complete response letter. [00:34:54] Speaker 04: So we don't know, as we stand here today, or certainly Vanda. [00:34:57] Speaker 05: Your Honor, you started off wanting to clear out the mootness. [00:34:59] Speaker 05: I'm telling you, you can't clear it out. [00:35:01] Speaker 04: And I'm trying to hold repetition to an evading review. [00:35:03] Speaker 04: Right. [00:35:04] Speaker 04: So two questions, I think. [00:35:05] Speaker 04: One, might it recur with respect to the development of tributant for the treatment of gastroparesis? [00:35:11] Speaker 04: That can only happen if Vanda elects to continue developing tributants for that purpose. [00:35:18] Speaker 04: There are no benefits from Fast Track if Vanda chooses to go up the agency appeal process towards judicial review. [00:35:25] Speaker 04: That's not what Fast Track is about. [00:35:27] Speaker 04: Fast Track is about having more meetings in the development process. [00:35:31] Speaker 04: With FDA so if they elect to say you know what FDA we think you got it wrong we're going to. [00:35:36] Speaker 02: Fast track when you're trying to expedite the process you'll get more meetings so why wouldn't that in and of itself. [00:35:44] Speaker 04: So those are meetings that pertain, again, to the development process, not with respect to the appeal process. [00:35:50] Speaker 04: And so if Vanda elects to do the agency appeal and ultimately try to get back in this court, Fast Track has nothing to do with that. [00:35:57] Speaker 04: Fast Track is only going to be relevant if they say, you know what, FDA, interesting points in your letter. [00:36:02] Speaker 04: Let's keep working together. [00:36:03] Speaker 04: And as my friend said, they have not committed to that. [00:36:05] Speaker 04: But more broadly on the point about this case being capable or this issue being capable of repetition, I think the critical point is that the question in this case is whether or not FDA properly applied the statutory standard to the set of data that was before it in February of 2022 when it denied the Fast Track application. [00:36:25] Speaker 04: Any further [00:36:28] Speaker 04: And now any further application of that standard will be to an entirely different set of data that, at a minimum, includes the results of the phase three study, and this much is public in Vanda's press release, a study that did not meet its pre-specified primary endpoint. [00:36:45] Speaker 04: And so any future consideration of Fast Track is going to be on an entirely different record. [00:36:53] Speaker 04: And so any determination from this court [00:36:55] Speaker 04: is not going to be relevant to that. [00:36:58] Speaker 02: And what's that determination with respect to priority review, though? [00:37:02] Speaker 04: I'm sorry, Your Honor. [00:37:02] Speaker 02: With respect to priority review, is that a different review than fast track review? [00:37:08] Speaker 04: So priority review is separate from fast track review. [00:37:10] Speaker 04: That's correct. [00:37:11] Speaker 04: Fast track gets you eligibility for rolling review, and then there's a separate standard for priority review. [00:37:16] Speaker 06: Here's the problem I have with your mootness argument, which is [00:37:21] Speaker 06: even before you get to the exceptions to mootness. [00:37:26] Speaker 06: The benefits of fast-track status are facilitate the development and expedite the review. [00:37:37] Speaker 06: of the drug. [00:37:39] Speaker ?: Right. [00:37:39] Speaker 06: So why isn't, why couldn't this be useful for, put aside for a second the clinical hold, which I want to ask you about. [00:37:48] Speaker 06: Of course. [00:37:48] Speaker 06: Just writ large, there's a pending application before FDA. [00:37:56] Speaker 06: You said in the complete response letter, not good enough yet, but everyone seems to agree that's part of an iterative process. [00:38:05] Speaker 06: And if we're not [00:38:07] Speaker 06: talking about development, we're at least talking about review. [00:38:11] Speaker 06: FastTrack gets them expedited review. [00:38:13] Speaker 06: That seems to keep the issue alive. [00:38:17] Speaker 04: So I think, as my colleague said, Vanda has not committed to what they're going to do in response to the complete response letter. [00:38:22] Speaker 04: In other words, I take that to mean they have not committed to continuing to develop this drug in consultation with FDA. [00:38:29] Speaker 04: And so it is not clear that there will be anything left to FastTrack. [00:38:34] Speaker 06: Right. [00:38:34] Speaker 06: I guess I'm trying to. [00:38:37] Speaker 06: I'm trying to separate in my mind the question whether the case is moot because you all just issued a response letter. [00:38:51] Speaker 06: Right. [00:38:51] Speaker 06: Or whether [00:38:53] Speaker 06: I'm not sure if this is a mootness issue, but or whether our getting involved is pointless. [00:39:00] Speaker 06: Let's just loosely say because they won't do the animal study. [00:39:03] Speaker 06: They seem to me different issues. [00:39:05] Speaker 04: They are different issues and I'm happy to talk about them. [00:39:08] Speaker 06: I'm skeptical about your mootness argument. [00:39:10] Speaker 06: I'm interested in the. [00:39:13] Speaker 04: animal studies. [00:39:15] Speaker 04: Let me please move to the animal studies. [00:39:17] Speaker 06: Am I missing something on the threshold? [00:39:20] Speaker 04: I think the critical point, the really critical point on threshold that I just want to underscore is that none of this matters to Vanda unless Vanda is going to continue working [00:39:31] Speaker 04: cooperatively with FDA to try to develop this drug leading into animal studies but put the animal studies aside like imagine that clinical hold had never issued and there was just a complete response letter that said you know we can't approve it yet here are the deficiencies period if certainly if vanda just says you know what we agree this drug doesn't work [00:39:50] Speaker 04: then this case is moved. [00:39:51] Speaker 06: Sure, but I mean, it seems like they want to work with you as much as they can without having to say, yeah, we'll do the animal stuff. [00:39:59] Speaker 04: I hope that Mr. Hughes can answer that question on rebuttal, because I heard him to say it's not yet clear if Vanda is going to work with FDA or seek a hearing before the commissioner, which again, leads to judicial review back in this court. [00:40:12] Speaker 04: The administrative appeal for which. [00:40:15] Speaker 04: Fast Track has nothing to do with that. [00:40:17] Speaker 04: Fast Track does not get you faster appeals or anything like that. [00:40:20] Speaker 04: So if they're going that direction, none of this matters and they haven't said yet. [00:40:24] Speaker 06: Well, but if they take the administrative appeal and then seek judicial review for. [00:40:29] Speaker 06: The current. [00:40:33] Speaker 06: What's the term CRL the response letter that. [00:40:36] Speaker 06: wouldn't preclude them from continuing the process with FDA going forward if they lose all that, right? [00:40:42] Speaker 04: I suppose that's true, but that's all speculation at this point. [00:40:45] Speaker 04: I haven't heard them commit to the fact that they're going to do that. [00:40:49] Speaker 04: It's their burden to show mootness, and it seems like they're still engaged. [00:40:53] Speaker 04: Let me also try to underscore the point then that [00:40:56] Speaker 04: Even if this court were to find that fast track was wrongly denied, again, in February of 2022, which I think I heard Mr. Hughes say is all the relief they're asking for, that would not be relevant to a future fast track request on additional future data that is necessarily going to be on a different record and is going to include the results of the phase three study that again, Vanda itself has said. [00:41:20] Speaker 06: It would structure the inquiry. [00:41:22] Speaker 04: Was not successful. [00:41:23] Speaker 06: it would structure the inquiry. [00:41:25] Speaker 06: I mean, they've isolated what seems to be a pretty clean and maybe interesting and close legal question about whether the fast track inquiry looks at the nature of the drug or also includes the ongoing negotiations with the agency. [00:41:43] Speaker 04: So I think the answer to that is that it would arise in such a different context that a judgment from this court would not be addressed. [00:41:52] Speaker 04: But let me move from talking, if I may, to that. [00:41:55] Speaker 04: Let's go to animal studies. [00:41:56] Speaker 04: Let's talk about the merits in animal studies. [00:41:58] Speaker 02: Quickly on that. [00:41:59] Speaker 02: Sure. [00:41:59] Speaker 02: The statute itself potentially makes this not moved, just because we talked about the expedited review and the facilitation and more meetings to be had. [00:42:10] Speaker 02: However, when you get to the issue about that they won't do the clinical studies, then that affects the remedy. [00:42:16] Speaker 02: So maybe we're here, but then there's nothing for us to do because they won't comply. [00:42:21] Speaker 04: So again, we are trying to make two separate arguments and mootness, which I've been talking about so far this morning. [00:42:27] Speaker 04: The argument is that in light of the complete response letter and pending further action from Vanda, there's nothing left to fast track. [00:42:35] Speaker 06: Okay, so putting that aside, let's talk about animal studies. [00:42:39] Speaker 06: Is that an alternative mootness argument or is it something else? [00:42:44] Speaker 04: I don't think it's a mootness argument. [00:42:45] Speaker 04: I think it's a merits argument. [00:42:48] Speaker 04: So our argument is that if you look at the statutory text, you know, which requires a demonstrated potential to address unmet medical needs, [00:42:57] Speaker 04: There are basically two elements there that are highly relevant and demonstrate why the decision here was correct. [00:43:04] Speaker 04: So first of all, it needs to be more than just a theoretical potential. [00:43:09] Speaker 04: It needs to be a demonstrated potential. [00:43:11] Speaker 04: And so FDA looked at the data that was... I'm sorry. [00:43:14] Speaker 06: This is just... Now you're talking about what the statute means. [00:43:18] Speaker 06: Right. [00:43:19] Speaker 06: I had thought there was a separate issue [00:43:24] Speaker 06: Not mootness and not what the statute means, but the point, even if they're right about what the statute means, if they're unwilling to do animal studies, like this dispute just doesn't matter. [00:43:39] Speaker 04: So their unwillingness to perform the animal studies, which is the basis for the clinical hold, which again cannot be challenged at this time. [00:43:48] Speaker 04: feeds into why FDA determined that they had not satisfied the statutory criteria for fast-track. [00:43:54] Speaker 06: I agree with that. [00:43:56] Speaker 06: I wonder whether it has independent significance. [00:44:00] Speaker 06: But all right, you can go to the merits. [00:44:03] Speaker 04: OK, so on the merits, the question is, again, have they demonstrated the potential to address an unmet medical need? [00:44:11] Speaker 04: And FDA looked at this in a very practical, fact-specific sort of way. [00:44:16] Speaker 06: Your position makes a lot of practical sense, but you said have they demonstrated the potential? [00:44:25] Speaker 06: And the statute says has the drug demonstrated the potential? [00:44:29] Speaker 06: And that seems like it's a not insignificant difference. [00:44:32] Speaker 04: So I guess I would answer to that. [00:44:34] Speaker 04: The potential to do what? [00:44:35] Speaker 04: And it doesn't say the potential to work in a test tube or work in a lab or have a particular chemical reaction. [00:44:41] Speaker 04: It says the potential to actually address an unmet medical need. [00:44:46] Speaker 04: And so if there are barriers that stand in the way of the drug being developed and being brought to market, those are barriers that relate to the drug and are going to prevent it from being able to address an unmet medical need. [00:45:02] Speaker 04: Another point I would make about about the relevance of the clinical hold as pertains to the drug is to emphasize that the clinical hold didn't just arise out of thin air. [00:45:12] Speaker 04: This wasn't just like a bureaucratic box checking exercise. [00:45:16] Speaker 04: It's explained in the appendix is that J I think 4 to 6 to 4 to 9. [00:45:20] Speaker 04: that there were specific reasons with respect to tradipotent based on existing animal studies to be concerned that there might be toxicity issues and therefore to want additional non-rodent studies before allowing the human trials to go longer than 12 weeks. [00:45:40] Speaker 04: And so our position is that the attempt to sort of divorce the drug from the drug development is really incorrect. [00:45:47] Speaker 04: And if the drug [00:45:49] Speaker 04: cannot ultimately have the studies that's going to lead to it potentially being approvable, then it's not going to be able to address or have the potential to address unmet medical needs. [00:45:59] Speaker 06: And that's the problem here. [00:46:00] Speaker 06: Your friend said there was an intervening statute which undercuts the basis for that. [00:46:09] Speaker 06: What's your next question? [00:46:10] Speaker 04: Yes, it's it's he does say that and it's a little bit puzzling to us because the clinical hold was litigated to find out to final judgment for judge Bates and didn't appeal. [00:46:21] Speaker 04: It did not raise a claim about the modernization acts in district court in this case. [00:46:27] Speaker 04: And if I could point the court to page 62. [00:46:29] Speaker 04: The modernization act was on the books at the time. [00:46:32] Speaker 04: At the time in district court, correct. [00:46:35] Speaker 04: Page 62 of the joint appendix. [00:46:37] Speaker 04: This is counsel Fervanda. [00:46:38] Speaker 04: I want to be clear. [00:46:40] Speaker 04: We're not saying that the question of what safety data is necessary or not is before this court, not at all. [00:46:46] Speaker 04: This case can't be a challenge to the clinical hold. [00:46:48] Speaker 04: That was litigated to finality elsewhere. [00:46:52] Speaker 04: If I could just very briefly make one additional point. [00:46:56] Speaker 04: In addition to the clinical hold, the determination letter that's in the record carefully explains the problems with the existing data that FDA had before it at the time, even putting aside the potential of getting additional data. [00:47:10] Speaker 04: And it explains that there were problems with the existing safety data because it didn't specify the treatment assignment, dose, [00:47:20] Speaker 04: patient, et cetera. [00:47:22] Speaker 04: That's at JA-335. [00:47:23] Speaker 04: And then with respect to effectiveness, it points out at JA-333, things like the definition of nausea-free days weren't specified. [00:47:34] Speaker 04: There was concern that patients were using rescue medication in addition to tredipitins. [00:47:39] Speaker 04: So there were problems with the data that existed before FDA at the time it made its decision, even putting aside whatever data was unable to be generated as a result of the clinical [00:47:51] Speaker 04: And so ultimately, this is a fact-specific, very careful scientific judgment about what data was before FDA. [00:47:59] Speaker 05: Are they not at least entitled to a judgment, assuming, looking at the case on your side, are they not at least entitled to a judgment that says, in response to one of the legal questions that at least I saw separating the parties, you suggested [00:48:21] Speaker 05: They've got to ask for fast track at the IND stage. [00:48:24] Speaker 05: They said they can ask for it at any point. [00:48:27] Speaker 05: They're at a stage now where they could argue we're at least entitled to have that, if that's a legal issue, to have that cleared up and say there is nothing that supports the agency's position that we're limited in any request for fast track treatment to the IND stage. [00:48:43] Speaker 05: The statute doesn't say that. [00:48:46] Speaker 05: It's not supported. [00:48:47] Speaker 05: And the court can issue a judgment on that point. [00:48:50] Speaker 05: Because there are things now that they may or may not do where the question of Fast Track could come up again. [00:48:56] Speaker 05: And if I were on their side, I would not want to face you saying, no, we're past the IND stage now. [00:49:03] Speaker 05: You've filed an application. [00:49:05] Speaker 05: We're not even going to consider Fast Track. [00:49:09] Speaker 04: I guess I'm not sure how that question is presented here, where Fast Track was requested at the IND stage. [00:49:15] Speaker 04: It wasn't. [00:49:17] Speaker 05: Do you think? [00:49:18] Speaker 05: It was not. [00:49:19] Speaker 05: That's the whole point. [00:49:20] Speaker 05: My understanding is, in reading your argument, you're saying, I thought your argument was, it must be, if you seek it, it can only be sought at the IND stage. [00:49:34] Speaker 05: And it was not. [00:49:35] Speaker 05: That's right. [00:49:36] Speaker 05: So my understanding. [00:49:37] Speaker 05: Suppose we rule that's wrong. [00:49:40] Speaker 05: Isn't that a legitimate judgment that they should get? [00:49:43] Speaker 05: That your position is not supported by the statute. [00:49:47] Speaker 04: I'm just not sure there's the daylight between the parties on that position. [00:49:52] Speaker 04: As I understand it here, FDA, excuse me, Vanda asked for Fast Track in October of 2021, which was well into the IND process. [00:50:00] Speaker 05: I can picture the pages that I'm reading where you have this long list of why it would make no sense to even think about Fast Track once we're at the stage where an application has been filed. [00:50:12] Speaker 04: Do you mean the NDA stage, Seanor? [00:50:13] Speaker 04: Is that what we're asking about? [00:50:14] Speaker 04: What you're asking about? [00:50:16] Speaker 04: So our point that we made in the briefs is that once an NDA has been submitted, there is no benefit. [00:50:21] Speaker 04: At the point when the NDA, when I say the application, that's what I mean. [00:50:24] Speaker 04: Yes. [00:50:25] Speaker 04: So perhaps we're talking past each other with respect to an IND and an NDA. [00:50:28] Speaker 05: Right. [00:50:29] Speaker 04: Our position is that there are no benefits of fast track that apply. [00:50:34] Speaker 05: OK, but you have not cited us to anything in the statute that supports the conclusion and therefore [00:50:41] Speaker 05: You must ask for it during the IND period. [00:50:43] Speaker 05: You haven't here and you're at the application stage and so you can't ask for it. [00:50:48] Speaker 05: Are they not at least entitled to a judgment that says your position is not correct? [00:50:52] Speaker 04: I don't think so because here they applied for FastTrack while an IND was pending. [00:50:56] Speaker 04: And then the point that we made in our brief is that once an NDA has been submitted, there's simply no benefits from FastTrack. [00:51:02] Speaker 04: And then certainly once a complete response letter has issued, then there are like really no benefits from FastTrack. [00:51:09] Speaker 04: But I don't think the question of whether a fast-track application can be made after the IND stage is presented here. [00:51:20] Speaker 05: Can be taken seriously by the agency. [00:51:22] Speaker 05: Can be considered. [00:51:23] Speaker 05: Can be acted on. [00:51:25] Speaker 05: Call it what you want. [00:51:26] Speaker 05: Your argument seemed to me to suggest that once you're at the application stage. [00:51:30] Speaker 05: At the NDA stage, correct? [00:51:31] Speaker 05: At the NDA stage. [00:51:32] Speaker 05: That's what I'm calling the application stage. [00:51:34] Speaker 05: I'm sorry for using the wrong term. [00:51:37] Speaker 05: Once you're at that stage, you said, at least, there's no point to this. [00:51:41] Speaker 05: That's correct. [00:51:42] Speaker 05: To me, that means, no, I'm not going to look at this. [00:51:46] Speaker 05: You were suggesting there's no statutory support for it. [00:51:50] Speaker 04: No, I certainly don't mean to be saying there's no statutory support. [00:51:52] Speaker 05: So you're not disagreeing with my suggestion. [00:51:55] Speaker 05: If it was in a judgment that says there's nothing here to support an agency position that they cannot consider a request for fast track, [00:52:03] Speaker 05: at the NDA stage. [00:52:05] Speaker 04: So I don't think we have said that, and maybe we need to double check our brief on this, I don't think we have said that you may not submit an application once an NDA. [00:52:17] Speaker 05: No, no, you didn't say they may not. [00:52:19] Speaker 05: It's consideration of fast track requests. [00:52:21] Speaker 05: What we've said is at the point of the fast track. [00:52:23] Speaker 05: I understand you saying it's pointless for us to be thinking about it. [00:52:28] Speaker 05: Now, this is the latest stage. [00:52:29] Speaker 05: Correct, yes. [00:52:30] Speaker 05: But that doesn't mean that as a matter of statute, they're foreclosed from trying. [00:52:36] Speaker 05: It doesn't seem pointless to me, having listened to the argument today, I can see good reasons why they might ask for fast track at this stage once an application has been filed, the NDA has been filed. [00:52:47] Speaker 04: So, and again, I want to underscore that here not only has the NDA been filed, it has received a complete response letter. [00:52:54] Speaker 04: So we're past the NDA stage at this point. [00:52:56] Speaker 05: And what I'm suggesting to you is maybe this is pointless. [00:53:00] Speaker 05: We're at a stage now where they may do something. [00:53:03] Speaker 05: When you say they, you mean vandal, Your Honor? [00:53:05] Speaker 05: Petition. [00:53:07] Speaker 05: We'll be essentially starting again. [00:53:09] Speaker 05: So the same question may come up again. [00:53:11] Speaker 05: And you may come back and say, there's no point to our considering now that an NDA has been filed. [00:53:17] Speaker 04: So I don't think we're saying that if Vanda were to respond to the complete response letter right by coming back at that point and saying actually guys you know what we want to continue working with you and we want fast and we want fast track they can absolutely make that request at least it took me a long time to get that clear in mind that may be me not you in any event that's certainly the way I read well if it's me I apologize but let me just underscore this me I apologize [00:53:40] Speaker 04: At least we're clear now. [00:53:42] Speaker 04: Thank you. [00:53:42] Speaker 04: I just want to be clear. [00:53:43] Speaker 04: Yes. [00:53:43] Speaker 04: If they decide, and to my knowledge they haven't yet, to continue trying to develop the drug, they can ask for fast track again. [00:53:50] Speaker 04: They haven't committed to doing that. [00:53:52] Speaker 04: As far as I know, it's going to be on a completely different record if they do. [00:53:56] Speaker 04: And they don't need a judgment from this court to ask for fast track again. [00:54:01] Speaker 04: If there are no further questions, we'd ask the court to either dismiss the appeal as moot or affirm. [00:54:07] Speaker 04: Thank you, counsel. [00:54:16] Speaker 03: Thank you, Your Honor. [00:54:17] Speaker 03: I'd just like to start with what must be a misstatement from counsel. [00:54:21] Speaker 03: He suggested the FDA Modernization Act existed at the time of the original clinical hold. [00:54:27] Speaker 03: That's completely inaccurate. [00:54:29] Speaker 03: I think he said at the time of the district court. [00:54:31] Speaker 03: At the time of the district court's decision. [00:54:32] Speaker 03: Yes, Your Honor. [00:54:33] Speaker 03: That's inaccurate. [00:54:33] Speaker 03: The district court's decision was January 31st of 2020. [00:54:37] Speaker 03: The FDA Modernization Act, as FDA points out in their brief at page 48, [00:54:42] Speaker 03: took effect in December of 2022, nearly two years later, it was legislation that was passed in 2022. [00:54:49] Speaker 03: This was legislation that Vanda worked for and lobbied in part on the basis of the district court decision that suggested more requirements for dog testing. [00:54:58] Speaker 03: Vanda, having got that decision, actively engaged with the legislative process to go to Congress to change the law. [00:55:04] Speaker 03: That law subsequently has changed. [00:55:06] Speaker 03: And FDA has never worked with Vanda to actually implement this in this case. [00:55:10] Speaker 03: So it's a little surprising that FDA is telling us something factually inaccurate. [00:55:15] Speaker 03: Moving on to the mootness issues, it's their burden. [00:55:20] Speaker 03: They have to demonstrate it. [00:55:21] Speaker 03: I can tell you now, though, Vanda is absolutely committed to moving forward with this drug. [00:55:25] Speaker 03: That is why we are here. [00:55:27] Speaker 03: The expedition and the facilitation requirements have every bit of bearing moving forward, as the court suggested. [00:55:34] Speaker 03: The NDA also is not over. [00:55:36] Speaker 03: If the NDA process were over, Vanda would have a right to be in court challenging the CRL if it chose as final agency action. [00:55:42] Speaker 03: We know under Nosham Pharmaceuticals, that's not the case. [00:55:45] Speaker 03: FDA can't say that it's not final to us a week ago or two weeks ago in other litigation and that it's final here. [00:55:51] Speaker 03: The NDA process is continuing to proceed. [00:55:55] Speaker 03: To step back, what is Fast Track designed to do? [00:55:57] Speaker 03: It is to take a drug that could actually help Americans with real needs and get through barriers. [00:56:03] Speaker 03: My friend focused on the existing development program barriers. [00:56:07] Speaker 03: There's no doubt the courts talked about it. [00:56:08] Speaker 03: There are barriers between with FDA. [00:56:11] Speaker 03: The purpose of Fast Track is to actually work collaboratively to get through those barriers because what Congress wants to do is help Americans who could benefit from a drug that has physical properties demonstrating its potential. [00:56:23] Speaker 03: That drug, Tridipin, it has that if it's judged via the proper legal framework. [00:56:28] Speaker 03: What we ask is the court to identify that legal framework. [00:56:31] Speaker 03: That's all the court needs to do. [00:56:33] Speaker 03: And then from there, we can work with the agency for all the other questions that resolve, but it's not moved and we think procedural barriers, right? [00:56:41] Speaker 06: You get meetings, you get expedited treatment, you get all of that. [00:56:45] Speaker 06: It doesn't change substantive. [00:56:50] Speaker 03: Well, I think there's a big difference between what I would call a resolvable issue that, for example, the hold-related issue. [00:56:57] Speaker 03: It's resolvable either because Banda could choose to do the study, or second, FDA could change its mind under the FDA Modernization Act 2.0. [00:57:08] Speaker 03: That is a resolvable issue. [00:57:10] Speaker 03: The question is, does the drug, is this the sort of drug that is worth [00:57:14] Speaker 03: trying to have the FDA and the drug sponsor work together because it has those properties. [00:57:18] Speaker 03: I mean, to go back to the Ovechkin example your honor gave about the potential, I think the question there is- Nothing about Ovechkin changes. [00:57:25] Speaker 06: There's just a rule that disables him from going forward. [00:57:29] Speaker 03: I think the question, your honor, is that to answer your question- That takes away his potential to break the record. [00:57:35] Speaker 03: So what I would ask in that scenario is, is there a procedure by which he can go to the NHL commissioner and [00:57:42] Speaker 03: apply to have a suspension. [00:57:45] Speaker 06: But that is the analog here is all about undoing a clinical hold. [00:57:52] Speaker 06: And I thought we had to just take that as established. [00:57:55] Speaker 03: No, no, your honor. [00:57:56] Speaker 03: And even the clinical hold doesn't mean the drug can't be approved. [00:58:00] Speaker 03: That is not a categorical barrier to drug approval. [00:58:03] Speaker 03: It's a critical barrier to how long you can say the drug for. [00:58:06] Speaker 03: But it's not a barrier. [00:58:07] Speaker 06: It can't be approved unless you do the animal study. [00:58:10] Speaker 03: Well, it goes to duration issue, your honor. [00:58:12] Speaker 03: It goes to how long it can be approved for. [00:58:14] Speaker 03: You don't have to have longer-term studies if you approve a shorter-term drug. [00:58:18] Speaker 03: So it is not a categorical- Or the unmet need for idiopathic- Gastroparesis, which- [00:58:24] Speaker 03: But which is what FDA told us that we should be looking to study. [00:58:28] Speaker 03: So it's not a categorical barrier. [00:58:29] Speaker 03: But the question and again, this gets to the purpose. [00:58:32] Speaker 03: If there are barriers, fast track is irrelevant for drugs that are sailing along that everything is great that FDA is giving two thumbs up on the development program. [00:58:41] Speaker 03: They don't maybe fast tracks helpful and that's fine. [00:58:44] Speaker 03: But that's not the purpose. [00:58:45] Speaker 03: The purpose is to take drugs that actually would help people but are not getting to market. [00:58:50] Speaker 03: to work with the sponsor and FDA to actually get those products to market. [00:58:54] Speaker 03: That's why it focuses on the drug, not on the development program. [00:58:57] Speaker 06: We understand any other questions from Mike. [00:59:01] Speaker 06: Okay, thank you, counsel. [00:59:02] Speaker 06: Thank you. [00:59:03] Speaker 06: The case is submitted.