Avenue Therapeutics, Inc. (NASDAQ:ATXI) Investor Update Conference Call June 3, 2019 9:00 AM ET
Joe Vazzano - CFO
Dr. Lucy Lu - President & CEO
Dr. Neil Singla - Chief Scientific Officer of Lotus Clinical Research
Conference Call Participants
Jonathan Aschoff - National Securities
Ed Arce - H.C. Wainwright & Co.
Good morning. My name is Natalie and I'll be your conference operator today. At this time, I would like to welcome everyone to the Avenue Therapeutics Conference Call. All lines have been placed on mute to prevent any background noise. After the speakers' remark, there will be a question-and-answer session. [Operator Instructions] Thank you.
And now, I'd like to turn the call over to Avenue's Chief Financial Officer, Mr. Joe Vazzano, you may begin your conference.
Thank you, operator. Good morning everyone and thank you for joining us today to review the Top line Phase 3 Clinical Data for IV tramadol and Patients following abdominoplasty surgery. You can access the press release we issued this morning by going to the investors section of our website, at www.avenuetx.com.
With me today with prepared remarks is Dr. Lucy Lu, our President and Chief Executive Officer. In addition, we have Dr. Neil Singla, who is an anesthesiologist, the Chief Scientific Officer of Lotus Clinical Research and a thought leader in the field of acute pain clinical trials. He is available for Q&A.
Before we begin, I would like to remind you that comments made by management during this conference call will contain forward-looking statements that involve risks and uncertainties regarding the operations and future results of Avenue in particular the success of IV tramadol. I encourage you to review the Company's filings with the Securities and Exchange Commission including without limitation, Company's Form 10-K, 10-Qs and 8-Ks which identify specific factors that may cause actual results or events to differ materially from those described in any forward-looking statements.
Furthermore, the content of this conference call contains time sensitive information, as accurate only as of the date of a live broadcast June 3, 2019, except as required by law Avenue undertakes no obligation to revise or update any statements to reflect events or circumstances after the date of this conference call.
I will now turn the call over to Lucy.
Dr. Lucy Lu
Great. Thank you, Joe. Good morning everyone and thank you for joining us to review the positive results from our second pivotal Phase 3 clinical trial of IV tramadol in patients following abdominoplasty surgery, the Phase 3 multicenter, randomized, double-blind placebo-controlled study evaluated the efficacy and safety of IV tramadol in 370 patients following abdominoplasty surgery, which is also known as a tummy tuck procedure.
Patients were randomized in a 3:3:2 ratio, so postoperative regimen of 50 milligram of IV tramadol, placebo, or 4 milligram of IV morphine at hours 0, 2, 4 and once every 4 hours thereafter, respectively for up to 13 doses over the course of 48 hours. IV morphine, a standard of care analgesic, was included in this study to obtain comparative safety data versus IV tramadol.
The primary efficacy endpoint of the study assessed the analgesic efficacy of IV tramadol compared to placebo as measured by Sum of Pain Intensity Differences over 24 hours or SPID24. The key secondary efficacy endpoint included Patient Global Assessment at 24 hours or called PGA 24, SPID48, and total consumption of rescue medication through 24 hours.
A key safety objective of this study was to compare the safety and tolerability of IV tramadol to IV morphine. In this study, IV tramadol 50 milligram achieved the primary endpoint of statistically superior improvement in pain relief as measured by the SPID24, a primary endpoint with P value less than 0.001 compared to placebo as well as meeting all of the three key secondary endpoints, each one of them are all significant at less than P less than 0.001.
IV tramadol and IV morphine demonstrated similar efficacy benefits in this study. In terms of safety, IV tramadol was well tolerated with no drug related serious adverse events in the trial. The most common adverse event greater than 10% were nausea, vomiting, headache, and dizziness. We provided the rates as well as placebo-adjusted rates in the press release.
Most adverse events were mild or moderate with only two patients experiencing a Grade 3 event, one of them was in IV tramadol arm and the other one in IV morphine arm. Study completion rates were high for all of the treatment groups with IV tramadol at 87.9%, morphine 91.4%, and placebo at 93.4%.
As you are aware, there is a clear need for new therapies in the postoperative pain setting where patients are often treated with Schedule II narcotics due to a lack of other options. Morphine, hydromorphone, fentanyl, oxycodone, and hydrocodone, they're all classified by the DEA as Schedule II control substance.
According to the DEA, substance dose is scheduled to have a high potential for abuse. We're very encouraged by the strong safety and efficacy results from our Phase 3 trial, which support IV tramadol's potential to provide any improved treatment option for postsurgical pain and to fill a significant gap between IV NSAIDs, acetaminophen, and Schedule II opioids.
IV tramadol also has the potential to provide a very convenient bridge to the widely prescribed oral tramadol, a Schedule IV controlled substance with less abuse potential and the lower rates of dependence than Schedule II conventional narcotics. These positive results from the abdominoplasty trial are meaningful milestones for Avenue as we have now completed the Phase 3 development program for IV tramadol.
Based on these results, we continue to plan to submit a new drug application with the U.S. Food and Drug Administration by yearend 2019. So let me conclude my prepared remarks today by expressing our gratitude. First, I would like to thank our patients, investigators, and their staff for participating in this study. Second, I'd like to thank our shareholders and our partner companies Fortress and Cipla for supporting Avenue and our efforts.
Last but not least, I'd like to thank Avenue employees for their hard work and dedication to this program. We wouldn't be here without all of you today. So, with that, I'd like to open up the call to your of questions. Please note that we will answer questions based on the topline results disclosed in a press release and will present and publish the full dataset at a future medical conference.
As Joe mentioned Dr. Neil Singla is available to answer questions as well, so with that, operator --?
[Operator Instructions] And our first question comes from the line of Jonathan Aschoff of National Securities. Your line is open.
Thank you. Good morning, Lucy, and the rest of the team and congrats on the positive Phase 3 results.
Dr. Lucy Lu
I was wondering what percentage of placebo patients used rescue and what rescue was allowed?
Dr. Lucy Lu
Sure, I'm happy to discuss what rescue was allowed. So, however, because we're going to limit today's discussions just to the topline results, we're not going to go into in-depth detail in terms of what percentage of patients used rescue medication. Please note that the amount of rescue medication used in the first 24 hours is a key secondary endpoint. So, IV tramadol deep [ph] placebo with P value of less than 0.001, so it is definitely a difference there and very significant, statistical significant difference there. So, the rescue medication allowed in this trial is ibuprofen 400 milligram up to once every four hours.
Okay, so it definitely explains that data table. Thanks. Would you -- can you tell me what the Grade 3 events were?
Dr. Lucy Lu
So, we have not discussed any of that, but it's something consistent with known pharmacology of these drugs, nothing surprising there.
Okay. And then before I ask my last question, I just want to make sure what you're developing is exactly the same in every formulation respect, as what is used in the EU, correct?
Dr. Lucy Lu
In the sense, that active ingredient, API 50 milligram of tramadol, that is correct. From country-to-country, I would just say that there are very small formulation differences. They're not absolutely identical in terms of some of the buffering agents in some of our formulations. They don't have to be always identical. But in general, I would say, yes. It is -- every single country that has IV tramadol in the market is 50 milligram of tramadol hydrochloride in a buffer solution, buffered solution.
My last question is that I'm just having a little difficulty reconciling the share price with the Cipla takeout, second stage closing price of almost $14 a share. And it just makes me feel like I'm missing something. So, with the takeout being triggered by FDA approval, I'm assuming a DEA schedule remaining at IV, labeling, which you might want to detail a little more for me? And the absence of REMS, can you outline for us some of these transactional details that might help us understand some risks to the second stage of the takeout that more importantly might help us understand a share price discount?
Dr. Lucy Lu
Right. So, it's a great question, Jonathan. Thank you for asking that. I think for those of us that work at Avenue, we have a very clear goal in mind, and it is to deliver FDA approval with all of the conditions satisfied for second stage closing with the Cipla team. So, we don't really watch stock price on a day-to-day basis, and we really have not gone out there to tell our story.
As you probably, I'm sure as you know, investor relations is a huge part of being a public company since signing us a Cipla transaction, we actually have not actively marketed ourselves, we have not really gone out to tell the story, so that could be some of it as well. But other than that, I mean, this is the 505(b)(2) NDA application.
Obviously, without the approval, a process is always at risk. But as of today, I don't think I can identify a special risk that we have that other companies don't have I mean. It's -- everything is falling into places as far as we know today. So, I think a lot of the stock prices, not measuring out, has to do with the fact that we just have not marketed ourselves.
And because of the Cipla transaction and also how busy we are this year, with completing the trial, preparing for the NDA, we just have not gone out and marketed ourselves.
And our next question comes from Ed Arce of H.C. Wainwright & Co. Your line is open.
Hi, Lucy and Joe, good morning and congratulations on our results.
Dr. Lucy Lu
Thank you, Ed.
So, just a couple quick questions for me, some of them have already been asked. But on the four main AEs that you listed in the table, just going through this numerically, it looks like there is a trend for slightly less event with tramadol versus morphine. Have you looked at the statistics around that? And can you share anything with regards to the analysis that you might do in that regard?
Dr. Lucy Lu
Sure, I'm happy to answer that, Ed. Thank you for the question. So, the question is on the AE table, whether or not we did statistical analysis to analyze to see if there's anything. So, I would just say that we definitely looked at the safety comparison between IV tramadol and IV morphine, and we reported the most common adverse events, which are nausea, vomiting, headaches, and dizziness.
Based on what we have in a table today, there is really no statistical significance even though tramadol really showed a lower incidence of some of these common side effects. So, we don't plan to perform statistical analysis on these numbers, but there's definitely an overall trend. I would agree with your assessment there that tramadol has fewer side effects than IV morphine, but it does reach statistical significance.
Okay very good. The other question I had, is, now that you've got both pivotal Phase 3 trials under your belt with positive results across the board, it does seem as though at least from a clinical risk perspective, this is now behind you. And obviously, the remainder of the year, we focused on preparing for the NDA submission. What components other than, yes, actual full analysis and preparation of the data -- what other aspects are you going to be working over the next few months to finish that application? In particular, I'm wondering if you could remind us around any sort of work that maybe necessary from a manufacturing or CMC perspective? Thanks.
Dr. Lucy Lu
Sure. So, over the next few months, we are just busy putting everything together. Ed, as you know, there's a lot of work to putting your data in a format that FDA accepts. So, we're going to be busy with that. On the CMC, we have a very good partner in supporting us. This is a fairly straightforward formulation on IV tramadol I'm talking about. So, we are just everything is -- all I can tell you is, as of today, everything is on track for a December submission, year-end 2019. So, we do think everything is on track. It's just -- it's a lot of work just to put things together. That's what we're going to be focused on over the next few months.
Dr. Lucy Lu
While we wait, we have Dr. Singla on the call, who is such an experienced and well respected expert in analgesic trials. He's an anesthesiologist by training. I just wanted to get maybe Neil, your perspective in terms of what you think the data as well as putting these in context. How you use every tramadol get that the approval? How you think physicians would use it?
Dr. Neil Singla
Yes, now, thanks for turning it over to me. Well, I couldn't be more thrilled it's a commission with the data. I mean, you design an experiment, and obviously, analgesic experiments at times can be difficult to conduct, et cetera. But the results here are so striking that I think it's just, it's a great outcome because not only do we see that the drugs are great examples of placebo, which is the standard for FDA approval, but we see the tramadol is behaving a lot like morphine. We see very equal efficacy and the great side effect profile.
So, from my perspective and these are my comments, not Avenue's, as a clinician, why would I want to use morphine, if I can use the Schedule IV drug that does the same work. So it's really exciting. It's also has an old component, as you guys know where so that we can discharge patients on that Schedule IV drug instead of having patients ever be exposed to the Schedule II drug, which is as far as I'm concerned, I'm very passionate about moving towards drugs with lower abuse potential.
So, I think that not only will clinicians to be excited, but the FDA will be excited in general, for society, this is a good step forward a significant step forward.
Dr. Lucy Lu
Great, thank you very much. Okay, so without, I don't think there are additional questions. So, I want to thank you all for your time and interest in Avenue. We are here, if you have additional questions, and we look forward to providing you with additional updates as the year progresses.
So, with that, we will conclude the call today. Thank you.
This concludes today's conference call. You may now disconnect. Have a great day.