Multiple Local Coverage Determinations (LCDs) Open Public Meeting - June 27, 2024 - JF Part B

Taylor Canova
Good afternoon, everyone, and welcome to Noridian's Open Public Meeting.

My name is Taylor Canova, and I am one of the Medical Policy Specialists here at Noridian Healthcare Solutions.

We will be presenting the following LCDs, Artificial Intelligence-Enabled Quantitative Coronary Topography (AI-QCT)/Coronary Plaque Analysis (AI-CPA), Botox Injections and Micro Invasive Glaucoma Surgery.

Before we begin the meeting, I would like to make the following announcements. This meeting will be recorded. The recording and written transcript will be posted on our website following today's meeting.

All lines are currently being muted and will remain muted throughout the meeting. Only those registered to present will be allowed to comment on the proposed LCDs today.

For the presenters, you are being allotted 10 minutes to make comments. your line will be opened when it is your turn to speak. Make sure you are not on mute within your system, or we will not be able to hear your comments.

You should be prepared to begin your presentation immediately when called upon and will hear the moderator's voice when one-minute remains. If you reach the end of your 10-minute time limit, your line will be muted, and we will move on to the next speaker in order to allow all registered commenters time for their presentations.

By signing in today, you are giving consent to the use of your recorded voice and your comments. Please be mindful of sharing any personal health information during your presentation. In addition to your comments that are made today, all comments should also be submitted in writing. All written comments received will be recorded in the response to comments article.

I will now turn this meeting over to Dr. Barry Whites. Dr. Whites, you may begin.

Dr. Barry Whites
Thank you. I do appreciate it. Can you hear me, okay?

I'll say that hopefully only one time.

Taylor Canova
Yeah, we can hear you fine.

Dr. Barry Whites
Great, great. First of all, thank everybody for coming.

Trying to get through the length of this first proposed LCD is probably going to be the hardest part that we have today.

The LCD policy was developed based on an LCD request for coverage analysis of quantitative coronary plaque analysis, QCPA, using artificial intelligence-enabled CT-based quantitative coronary topography/coronary plaque analysis.

That's a mouthful. And everyone, I'm sure, has been through this that's going to speak today, and hopefully most of you have reviewed this.

This is somewhat of a narrow policy based on the evidence that, at the time of beginning this, was not terribly accepted in the intermediate risk of no known on coronary artery disease and a negative evaluation and that had been clearly identified as being a potential elevated risk, others, and we're sure that the categories will be added as this technique and this technology is expanded and more studies come in, but this is the area, and the reference is so listed here.

The plaque composition has emerged as evidence to provide information that can aid in the identification of the at-risk group and other additional management options to reduce risk. The addition of plaque quantification was demonstrated to prove the diagnosis and prognostic risk stratification beyond the capability of the CCTA of the Coronary Computed Tomography Angiography alone.

The symptomatic patients with intermediate risk and no known coronary artery disease is mentioned and negative evaluation have been identified as the group of potential elevated risk.

Chest pain guidelines support this role of plaque assessment in this group of further patients to delineate risk and offer escalating intervention if needed indicated. This is supported by strong recommendation of quality 1A as mentioned.

We will begin our evaluation, excuse me, our conversation with the commenters on this policy and we certainly do appreciate your participation.

Next slide.

Dr. Arish Nayeri, you're up next.

Dr. Arash Nayeri
There we go. Thank you for having me.

I'll start my 10 minutes now.

So, thank you for having me.

My name is Arash Nayeri. I'm a cardiologist at Cedar Sinai, and can we go to the next slide, please?

Are you guys controlling that?

You guys are well aware of this, you know, cardiovascular death remains the number one cause of death in the United States. It has tremendous public health implications, and it has tremendous financial implications with many different estimates of its increasing financial cost to our system. By one estimate $366 billion by 2035 and killing roughly one in five people.

Comments we want to make is, despite all the stress tests we do, over 10 million done annually, which are only there to possibly detect obstructive coronary artery disease, we know most cardiac events occur in patients with non-obstructive disease, so we need different testing modalities to identify and hopefully prevent events.

Next slide, please.

So, you know, there's been tremendous amount of data, as many experts on this panel can opine that disease and plaque predicts events, and this is data from just even the calcium score, knowing that the higher the calcium score, the higher the risk of having an event, and for patients with a calcium score of over 300, for example, we see their rate of having an event in the future is very comparable to people who have previously had an atherosclerotic event.

Next slide, please.

There are limitations to calcium score and based on one estimate published in circulation in 2020, about a third, maybe a fourth of all cardiovascular events happened in people at a calcium score of zero. And we know it's not symmetric some people have a higher risk of having a disease, even obstructive disease, with an undetectable coronary calcium and again, it affects different patient populations, predominantly women and younger women. So, stress tests are not perfect. Calcium scores are useful, but not perfect. Next slide.

And this is where I think we've seen the increased use of coronary CT angiography.

The DECODE study, I think, can highlight maybe some of the utility of CT plaque analysis.

So you take patients with what you would think would be known cardiovascular disease and based on just a human read of a coronary CT report, you see out of 100 people, fairly heterogeneous, you know, risk factors, age, so forth, 94% of them, based on human read, were put into stage two. But if you use CT-enabled artificial intelligence plaque analysis, you could see you reclassify 66% of patients' management and one thing I want to highlight here is almost 50% of those patients had a coronary calcium score of zero, and almost, not almost, 40% of them were CAD-RADS-1.

Next slide, please. Next slide, please.

So again, why do we care about plaque analysis and plaque volume? Because it provides incremental information, we know patients with more plaque have higher risk of events those are people that maybe we want to consider for many more of these novel and developing therapies we have for the management of atherosclerotic disease.

Next slide, please.

So, this is, again, talking about how plaque informs risk. We know having more plaque predicts a higher risk of event. So, in this model, just looking at inflection point of 238 millimeters cubed, you see a hazard ratio of 7.3 and then there's other things about plaque analysis, not just plaque volume, that can predict incremental risk can be risk modifiers such as identification of low attenuation plaque burden, which can have a hazard ratio of almost five.

Next slide, please.

And we know the analysis of plaque can be used to guide therapy, and we get to look at then response to therapy such as statin and non-statin related options for the detection of progression of calcified or non-calcified plaque in patients who may undergo serial imaging.

Next slide, please.

So, this is why I think we're excited about this toolbox and why we're here. I think we can use AI-CPA to get an insight about where the patient is, how much plaque they have, where the plaque is, and what are the characteristics of the plaque. We can interpret that in the context of population standards with the help of a normogram, and again, we can use some of the information we get based on total plaque volume, burdenable attenuation plaque give, you know, much more individualized assessments of patient risk.

And again, CAD-RADS recommends varying level of risk factor modification based on level of plaque, so this can really help us tailor our management for our patients on an individualized level.

Next slide, please.

So I have a quick case example of, you know, one case where I think this has been useful and for the sake of time, we're just gonna do one case, but I had a 60-year-old gentleman who was previously diagnosed with HFpEF, and then came to me about a year later with a diagnosis of HFrEF and here's a guy who has had prior stress tests, nuclear stress tests, which was unremarkable and he actually, in fact, a year and a half prior had a coronary CP angiogram for atypical chest pain, which was interpreted as a non-obstructive disease.

And the gentleman had multiple risk factors for coronary artery disease and its progression, sex, obesity, diabetes, hypertension and we managed his heart failure we did one medication at a time on this guy who was more medication hesitant and avoidant, maybe intolerant, but after about four months of therapy, he came to us with, again, some atypical chest pain and increasing burden of PVCs on serial EKGs.

Next slide, please.

So, we sent him for a repeat assessment with a coronary CT, and this was his CT, you know, good image quality, slow heart rate, and here's what we saw. The human read, you know, calls him left dominant, I'm sorry, right dominant. The only obstructive disease we noted, and just based on our read on the coronary CT, was a 90% stenosis in a non-dominant circumflex.

And every other plaque, based on our interpretation, was less than 50%. So, here's a guy I would contend, many cardiologists would tend to manage medically. Because again, the obstructive disease seems to be in a smaller caliber vessel, and it does not really explain his total cardiomyopathy, but this is where AI-CPA can add additional value.

So, it reclassified the LAD stenosis, for example, on approximate LAD to 50 to 69%, not less than 50%.

Next slide, please.

And again, gives us more information, gives us a sense of his total plaque volume and what stage he may be and in the LAD, when it up classifies him to maybe up to 50 to 70% stenosis, we see he has a higher burden of low attenuation plaque, which has been consistently associated with a higher risk of plaque rupture.

Next slide, please.

So, I discussed the case with him we discussed the advent of the technology and we talked about how he may have underestimation of his disease, you know, in the LAD, and even if it's not underestimated, that that's disease that could have markers for future risk of plaque rupture, such as low attenuation plaque burden and positive remodeling.

Shrugged thereafter, he was having chest pain, again, atypical chest pain, but chest pain.

And here's a guy who's undergone serial stress tests, which were previously normal, and a CAT scan and without the help of AI-CPA, which again would not have delineated a very high risk of having an event. He underwent angiography and PCI of a subacute rupture in the proximal LAD, and he miraculously had a market improvement in his LV systolic function.

After that, this is just one case where I think AI-CPA can lead us to pursue different management, medical, maybe even invasive.

Next slide, please.

So, I think we have two asks.

One is, I think the language would be appropriately updated to include patients with stable chest pain. A lot of studies we've shown today include patients with stable chest pain, and I think the guidelines, the AHACC guidelines have recommendations for stable chest pain, you know, even without known or with known delineation of anatomy in the past.

Next slide, please.

And I think the last ask we have is consideration of including patients for CAD-RADS-1 because again, the management strategy, the code, for 40% of people with that level of disease was still changed with the use of this technology.

Thank you for your time.

Dr. Barry Whites
Thank you so much for your presentation, very enlightening.

Again, just another reminder is that you will need to submit in writing. We've got your slide presentation, but any other additional information, particularly the items that you would like added, the comments in what form, also any documentation that you have to support your slides and the contentions on the slides will certainly be needed and welcome.

So, thank you so much.

Next, Dr. Matthew Budoff, please.

Dr. Matthew Budoff
Yes, thank you.

Thank you for allowing me to speak on this.

If I can go to the next slide.

So, I've been a user of cardiac CT since 1990. It's been part of my practice. I'm a professor of medicine at UCLA and I've been an active participant in a lot of the studies that were just recently presented, but I've been using this tool clinically now for a number of years and have used it in hundreds of my patients personally, and it has very favorably changed my patient management.

I think that we have excellent data, and as you mentioned in the opening statements, that this LCD is consistent with the American Heart Association American College of Cardiology chest pain guidelines published in 2021 by Dr. Gulati at Cedars-Sinai, as well as in the American College of Radiology guidelines, which actually I was a co-author of with Dr. Cury in 2022, and both of these guidelines call for a use of this plaque-based assessment because of a lot of the things that we just heard from is that it can change patient management, that we can see the plaque in a more comprehensive way and change how we would treat our patients. And in my practice, it's led to less cardiovascular events and better patient outcomes and also patients understand their own risk, which I think is really, really important because we're asking patients often who are now feeling better after their hospitalization to take medications for a number of days or weeks or months or and ultimately we need them to take them for years. So, we need them to stay on therapy.

We've been able to show with this algorithm of care that it not only changes patient management as you just heard, but also decreases healthcare costs by leading to less downstream procedures like cardiac catheterization. We can prevent outcomes, bad outcomes like MI, stroke and cardiovascular death. It risk stratifies, it helps us identify who's high risk and who's low risk, so we can apply more therapies to the high risk people, but also, very importantly, save money by not applying high risk therapies or expensive therapies to people who we now understand are not high risk, but are actually low risk based on plaque assessment.

Next slide.

So, while I'm very strongly in line with the proposed LCD, I would like to suggest two changes.

Next slide.

The first change that you just heard about was a stable chest pain.

Actually, most of the data with plaque and with cardiac CT actually comes from stable chest pain studies, the SCOT Heart trial, the PROMISE trial, and many other studies that have been done over the past two decades have been done in stable chest pain, and this is the larger benefit for our patients.

When patients come in with an acute chest pain syndrome, they can often be sent to the cardiac cath lab and be dealt with it urgently.

In the outpatient arena where patients have stable chest pain, we're trying to avoid the need for invasive angiography and expensive and invasive tests and try to just manage them medically, and we can identify those patients much better if we understand their plaque and their stenosis severity.

Next slide.

So, this mimics what you just heard with the previous presentation, on the bottom right is a trial called SCOT Heart. SCOT Heart was actually done in over 4,000 patients with stable chest pain, and when they underwent CT angiography and they had plaque assessment, there was a 41% reduction in fatal and non-fatal myocardial infarction.

As you can see, compared to the red line at the bottom right curve, there is event benefit by understanding the plaque and the stenosis severity, and the guidelines, the American Association, the American Heart Association, and American College of Cardiology chest pain guidelines recommend this test as strongly in acute chest pain as stable chest pain.

So just like the LCD already nominates acute chest pain, we need to include stable chest pain, those outpatients that are coming in with chest pain that need accurate assessment. So we know not only do we triage them to the hospital or do we triage them to no medical therapy, but also how aggressive to be in our management of these patients to avoid the most expensive and poor outcomes, things like heart attacks and strokes from occurring, and we've been able to document that in a number of clinical trials, not only SCOT Heart, but other studies as well. And you can see the language in the LCD, I mean, in the guidelines here, 2A recommendation for symptomatic patients with known non-obstructive disease who have stable chest pain, CT angiography is reasonable for determining plaque burden and progression and guiding therapeutic decision making, which I would argue I do every day with this tool, and it's a very valuable addition to my treatment algorithms, as well as and I know many, many other doctors in the community.

Next slide.

The other place is the language where we talk about known CAD. The language in the LCD talks about non-obstructive disease where we want to focus our attention on including patients with non-obstructive disease, so they have to have some plaque, you can argue plaque present on CT angiography, right now the LCD focuses on CAD-RADS 2 and 3, which would be a 25 to 75% stenosis.

I think you can think about some patients with lesser plaque might have a severe plaque burden and benefit from more preventive therapies we have so many great therapies now with cholesterol management and blood pressure management and anti-inflammatories that we can apply if we understand the plaque burden.

Next slide.

Krista Babbitt
Sorry, that was all that I had for you.

Dr. Matthew Budoff
Oh, I thought I should have one more side.

Well, anyway, let me just mention it.

So the other issue is the concept of known coronary artery disease, I think in the LCD, there is a language that says that this should be limited to a known CAD and the language is now, the LCD language is acute chest pain, which I think we need to add stable chest pain and then the second part of the language is no known coronary artery disease.

And I think that that's a very vague statement that's gonna lead to a lot of confusion by everybody, by both the payors and the people approving the test, as well as the doctors who are ordering the test.

The definition of coronary disease is very vague, and I would suggest we make very specific language so that it's very clear that this test is not useful in patients with prior myocardial infarction or prior revascularization, but coronary disease, it can be interpreted in many different ways by many different doctors, and the SCOT Heart study included patients with quote known coronary disease, and you can argue that's a little bit of plaque, you can argue that's a 50% stenosis, you can make a lot of different assumptions about what that means and I think we wanna say that this test is not useful uh, in, um, prior myocardial infarctions, we know what to do with those patients we know they need to be treated aggressively uh, if they've already had a stent or bypass surgery, this test is not appropriate, but for other patients who might have just blockages in the arteries, that's CAD-RADS-3, which it's already being proposed to be used in, so I think we need to clarify that language for both us as ordering doctors and for you as the doctors that may be approving the test and ultimately reimbursing for the test.

So, with that, I will stop and thank you very much for your attention today.

Dr. Barry Whites
Thank you, sir.

Next comes Dr. James Min, Cleery Health.

Please proceed.

Taylor Canova
I don't show that he's on.

Krista Babbitt
Yeah, we can go to the next one.

Let me run through his slides.

Dr. Barry Whites
Dr. Campbell Rogers, HeartFlow, please proceed.

Thank you.

Dr. Campbell Rogers
Great, thank you, can you confirm that you can hear me okay?

Dr. Barry Whites
Yes, we can, thank you.

Dr. Campbel Rogers
Right, sure.

So, first disclosure, I'm the Chief Medical Officer at HeartFlow, I'm a full-time employee of HeartFlow.

If we go to the next slide, please.

I would like to echo the earlier presenter's recognition of and gratitude for the rigor that's gone into this draft coverage determination, it really is extremely well thought out, broad, well referenced.

There are a couple of areas that I'm going to suggest perhaps revisiting some of the choices that have been made, some of the language, but overall I want to recognize the work that's gone into this and how important it will be for Medicare beneficiaries to have access to these tools and to this growing area.

If we go to the next slide, please, and skip beyond this, this was already discussed.

I do want to highlight just as an introduction that over the last several years there has really been a burgeoning literature on this area of quantified coronary plaque, and in particular, I would call out recognition in the ACC, SCCT, and American College of Radiology, and RSNA guidance and consensus called CAD-RADS 2, which is referenced and used in the draft coverage determination.

What you see quoted here, which is the following, and this really sums up really a huge amount of literature, that there is substantial data demonstrating the overall amount of coronary plaque, the actual amount, as a strong association with incident coronary heart disease events, and that such information may offer stronger prognostic value than merely the presence or absence of anatomical stenosis or clinical variables, and really, this observation underlies what we're here to talk about today and the subject of this coverage determination.

You go to the next slide, please.

By way of introduction to what this actually looks like, this is an example of HeartFlow's quantitative plaque analysis, and it includes both quantitative data, the number of cubic millimeters of plaque which exist in each of the coronary arteries, and obviously a patient-specific way, as well as patient-specific images showing the arteries and where the plaque is and then finally, on the right, information derived from large population surveys that put this in context.

So, for a woman at the age of 50, X amount of plaque equates to the such and such percentile for 50-year-old women, for example, so all of this is now included in these analyses as is being discussed by this coverage determination.

You go to the next slide, please.

There is really strong literature, including some of which has been published even since the draft coverage determination, which of course we will be submitting and written, providing in written comments as instructed at the beginning of this meeting, including looking at accuracy of these tools in terms of, in the light of reference standards, clinical reference standards, in this case, intravascular ultrasound.

So intravascular imaging of coronary plaque right at the site and then comparing those numbers to what's found with these AI quantitative plaque assessment tools.

You go to the next slide, please.

Also important, and this was referenced by one of the earlier discussants, is the way in which these tools modify patient management and of course, this notion of true utility is so critical to thinking about how diagnostic tests may influence patient outcomes, so for reference, for example, the Decode publication, which is referenced in the draft LCD identified that when provided this quantitative information, physicians changed their management plans for patients in over a half, up to two-thirds of patients, just by virtue of the added information provided by the AI-CPA tools.

Go to the next slide, please.

And you can skip past this.

We discussed this, please.

Next one.

Great, thank you.

And the next slide, please.

There are two areas we would suggest revisiting, and again, we'll submit all of this in the written comments as instructed.

The first is as follows.

The current draft coverage reads that patients present with acute chest pain and no known coronary artery disease, et cetera. We suggest this be updated to the patient presents with stable or acute chest pain, et cetera. The other speakers have provided similar comments and rationale for this.

If you go to the next slide, please.

The rationale that we would point to is as follows.

The first key point is that AHA ACC guidelines for diagnosis of chest pain support use in both populations, both being stable chest pain and acute chest pain and the information here across the guidelines, I won't go through it one by one, but across guidelines.

This is consistent that stable chest pain is a key population where benefit for these technologies lies.

Second at the bottom, just more on a sort of tracking purposes, having stable and acute would also be in line with other parts of this same LCD and similar LCDs, and what I mean by that is at the very bottom of this slide, the draft LCD states that patients should be eligible for CTA, which should, quote, be performed in patients with stable coronary symptoms. So that exact variation is inconsistent with the absence of stable in the other parts of the LCD.

And finally, at the very bottom of this slide, another LCD for non-invasive fractional flow reserve, so-called FFRCT, is considered medically necessary for both acute and stable chest pain, as the guidelines include as well and again, changing it here will make for internal consistency across this family of coverage policies.

Go to the next slide, please.

Our second and last suggested revision is as follows.

The current draft reads, the patient presents with acute chest pain, no known coronary disease, and is classified as one or both intermediate risk or CAD-RADS-2 and CAD-RADS-3 category, and that has to do with how severe the narrowings are, not the volume of plaque, but the narrowings.

We suggest this be updated to the same preamble, but CAD-RADS-1, CAD-RADS-2, CAD-RADS-3, or CAD-RADS-4 category on CTA, and for those not familiar, these refer to CAD-RADS-1 patients who have coronary disease but may not have as severe stenosis, CAD-RADS-4 patients who have more severe stenosis than CAD-RADS-2, 2, or 3. So, we suggest these be added, and again, there's some clerical notes at the bottom. This would require changing another part of the LCD from 70% to 99% and eliminating the CAD-RADs-4 reference in the coverage limitation section.

Go to the next slide, please, which is my last slide.

The rationale for this change is as follows, if one looks in the DECODE study I mentioned earlier and was mentioned by one of the earlier speakers that if you say, how often does this information change treatment in patients who are currently excluded from the draft LCD?

How often does it change physician management, physician behavior?

In CAD-RADS-1 patients, in the DECODE study, 40% of patients had their management change by virtue of this information, of CAD-RADS-1, and at the other end of the spectrum for CAD-RADS-4 patients, 94% of patients with CAD-RADs-4 stenosis had their management change made more intensive after the AICPA information was available.

So based on this utility and these groups, which are as of the draft LCD excluded from coverage, we would suggest that these be added to the coverage determination.

So, with that, I'll conclude again, thank you so much for the opportunity to participate in this meeting.

Dr. Barry Whites
Thank you very much. My screen is limited Dr. Ahmad, I cannot see your last name. It's hidden with another item if you would proceed. Just state your full name, please, sir.

Dr. Ahmad Slim
Hi, sorry. Yeah, it's Ahmad Slim, I'm here on behalf of SCCT as well as being a practicing cardiologist in the Pacific Northwest within the Noridian region, practicing with the Pulse Heart Institute.

Next slide, next slide.

I will not belabor the point, there's definitely a lot of evidence that's been presented throughout the afternoon in regards to outcomes as it relates to a non-obstructive disease and the type of plaque that's associated with it.

I know that everyone on the call is a cardiologist, but really the bottom line is we've always looked for that holy grail for blockages that can increase risk of heart attack or myocardial infarction but not necessarily in need of a stent, or there are patients that get a stent to relieve symptoms, but as you know, stents don't make heart attacks less, so where plaque comes in is that it helps us find that population and be able to treat them well.

Next slide.

This is a little bit of an oversimplification, but to kind of walk you through the process, patient has chest pain, stable or acute, they undergo a CTA, about 40% of these patients will not have any plaque, and these are the patients that go on their merry way.

We look for other reasons for chest pain and primary prevention.

And about 60% of the patients will have some sort of plaque, whether it's CAD-RADS-1, the minimal disease all the way to 5, but just it's misleading when you say the word minimal, right in 1, because you're not really evaluating the plaque, the consistency, the degree of it, and the impact as it relates to that patient. So in that population, and the focus will be on use of plaque beyond stenosis and I think that's the key word, stenosis is the degree of obstruction that affects the symptoms of chest pain versus the plaque and the type of plaque helps us predict what's going to happen and how can we mitigate that risk.

Next slide.

So, really, we get the result, we review it, we take a look at it, we identify the total plaque there are different nomograms that could be used and then we alter treatment based on that and as a result of it, reduce outcomes, and as you can see with the CAD-RADS guideline that was generated by SCCT, one of the biggest components of the reporting is the degree of plaque reported from P1 to P4, and it helps guide the treatment and the pharmacotherapy beyond the degree of stenosis and the management to that point.

Next slide.

So again, there's been a lot of evidence that was presented, we'll share a lot of that evidence with Noridian.

The society is recommending the inclusion of stable patients into the population and that's just simply based on everything that was presented along with the guidelines.

Next slide.

And this is just a summary of the guidelines with recommendations for stable chest pain, again, this has been presented by other presenters earlier, so I will not belabor the point.

Next slide.

The key thing for us is the inclusion of the population with CAD-RADS-1 and 4. These are patients that will still be at risk, these are patients with plaque composition that put somewhat of higher risk than everybody else and will not be any less risk just by virtual being in one category versus the other, and being in a CAD-RADS-4, the degree of stenosis is for the management of the chest pain and majority of these patients are potentially managed medically.

So, the intent is to really decrease the risk of future heart attacks or myocardial infarction and that's why the guidelines and CAD-RADS specifically recommend the description of plaque in both categories.

Next slide.

And the next slide is just a reference as it relates to the guidelines and the recommendation for description of plaque and management as it's adjusted for both CAD-RADS-1 as well as CAD-RADS-4 by a sighted cardiovascular CT.

Next slide.

This is the end of it. I tried to keep it as simple as I can be, and hopefully it will drive the point that everyone else has been trying to discuss today, which is inclusion of the stable chest pain population as well as inclusion of patients with CAD-RADS-1 and CAD-RADS-4 who will truly need the technology as much as CAD-RADS 2 and 3.

Thank you for your time.

Dr. Barry Whites
Thank you so much. And again, submission of all your documentation to us would certainly be appreciated if you want to be considered. Thank you.

Next, turn it over to Dr. Moynihan.

Dr. Eileen Moynihan
Thank you.

I'm guessing that we can't get Dr. Min back, so we're going to move on to Micro Invasive Glaucoma Surgery.

This, quite a while ago, many of the contractors had policies on Micro Invasive Glaucoma Surgery, technology has changed a little bit, and those policies needed to be updated, but an earlier version was presented at open meeting quite a few months ago. We received many, many comments on that version and also received 239 or so additional updated articles.

It took quite a while to go through all of that evidence and following that and discussion with the work group, you have before you the updated collaborative MIGS work group LCD that all contractors will be presenting at open meeting, so I think we have one presenter, Dr. Maltzman.

You want to go ahead, please?

Dr. Jeff Maltzman
All right, great. Are you able to hear me now?

Dr. Eileen Moynihan
Yes, I am, thank you.

Dr. Jeff Maltzman
Thanks very much, you can move on to my slide deck, I suppose.

I'm Jeff Maltzman I'm a practicing ophthalmologist, glaucoma specialist in Tucson, and I'm representing the listed organizations here.

Next slide.

No relevant disclosures to anything that I'm talking about here today.

And next slide, please.

So, I just wanna begin by expressing our tremendous appreciation for being able to work with the Contract Medical Director Work Group over this past year on this policy, as you pointed out, lot of information changed hands and we appreciate that.

I think the iterative public comment process has resulted in a proposed LCD that we believe reflects current practice patterns and that will allow physicians and patients to make treatment decisions that work best for the individual patient needs.

We also very much appreciate the addition of the section on healthcare disparities, which appropriately highlights the disproportionate disease burden of glaucoma on minorities, particularly African-Americans and Latinos, and we wholeheartedly agree that additional research is needed in that area to better understand those differences in treatment outcomes and that future research absolutely has to include more diverse study populations.

So again, our societies appreciate the opportunity to present briefly today and offer a few additional recommendations to further improve and clarify the proposed policies so that all glaucoma patients can be afforded access to treatment that best suits their specific needs.

Next slide, please.

So, we agree with the proposed coverage of stents as described in the indications of coverage, though it's likely just a typo, in number two, we note that the correct terminology that we're looking for here is subconjunctival, not supraconjunctival, this is purely a clarification issue. These devices that we're talking about drain aqueous humor to the space under the conjunctiva, or the subconjunctival subconjunctival space in order to reduce pressure in the eye. So that's just a minor change, but an important one.

And further, while phacoemulsification with a single MIGS procedure is indicated as covered in the limitations of covered section of the document, for clarity, we think it makes more sense to include it here in the indication of coverage sections, so we recommend using similar language, similar coverage language that's already found within the LCD and creating a third bullet point, as noted here on this on the slide.

We'll go to the next one, please.

And as a result, then corresponding changes to the limitations of coverage would be made for limitation number two, we just request a slight clarification there we recommend changing the word patient to the word eye, because glaucoma is typically bilateral and there could be a need for bilateral procedures. We just want that to be clear to physicians and payers.

And for consistency and clarity, again, we recommend that limitation number three, read a Phacoemulsification/Interocular Lens Placement performed with a combination of MIGS procedures, such as cataract plus stent plus, canaloplasty or goniotomy, at the same time of service is not covered. The intent remains the same, just non-coverage of multiple MIGS procedures with cataract surgery, but we think that this language would be a little clearer to physicians and coders reading this policy.

Next slide, please.

Although we understand that that current limitation, number three, is the present policy, and we agree with that, our organizations do call your attention to a growing body of evidence that shows improved outcomes and patient experience when MIGS procedures are combined.

Here in a 2023 study by Dixon, et al found significantly greater reduction in the need for glaucoma medication while maintaining similar rates of intraocular pressure reduction and low complication rates when cataract surgery was combined with stents and canaloplasty, in other words, to combine MIGS procedures, as opposed to cataract surgery with stents alone.

And although there currently isn't enough evidence to combine procedures, we do believe that such strong evidence is likely to grow steadily as more and more studies are being done on this particular topic, so not only can the reduction in glaucoma medication improve patient quality of life, it may also ultimately reduce costs to the healthcare system.

So, we simply ask that you remain open to ongoing review of the data regarding these procedures as they will likely develop over the next few years.

We feel it's important for a surgeon to have this tool in their kit for patients who may benefit from reduced or eliminated medication burden.

We can go to the next slide, please.

And lastly, we appreciate the list of definitions included in the LCD, because it certainly allows us all to speak the same language, and with that goal in mind, we do encourage you to update the definition of refractory glaucoma to align with the definition agreed upon by and established by our combined societies in a 2021 consensus statement.

While it's similar to the proposed definition, we do feel the additional specificity in the consensus statement definition reflects how most glaucoma specialists think about the disease, and while this particular definition focuses on medical treatment.

We do agree with your proposed definition to also include the failure of surgical treatment.

And then the last slide, please.

So basically, in summary, patients with glaucoma, which does disproportionately impact black and Hispanics, need access to a broad range of surgical procedures. Again, our organizations appreciate that this is generally recognized throughout the proposed LCD.

For many of our patients, treatment with medications is inadequate, and yet their glaucoma isn't at a stage requiring more invasive and potentially more complicated procedures, such as trabeculectomy and tube shunt, more traditional glaucoma surgeries.

For these patients, MIGS procedures do help preserve their quality of life and ultimately reduce total costs to the healthcare system.

We support further studies to investigate the indications for combining cataract surgery with more than one MIGS procedure, again, such as cataract plus a stent plus a canaloplasty or goniotomy, and we ask that the carriers expand coverage when more outcomes data are available and has been suggested previously. We look forward to continue this dialogue, and we will be submitting all formal comments with PDF copies of studies on multiple MIGS procedures combined with cataract surgery and any other relevant information. That's about all.

Thank you very, very much for your time today.

Dr. Eileen Moynihan
Thank you, Dr. Maltzman.

One good thing is that so far, I don't have all the comments yet, but this is looking a lot better than the last time but thank you.

Dr. Jeff Maltzman
It's good to hear. Thanks.

Dr. Eileen Moynihan
And you know that all the LCDs are living documents because they can certainly be reconsidered with new literature. And so, we'll welcome that, but I do hope that we get a slight break so that I don't have to read this for the 600th time and try to correct the grammar too soon. Can I have the summer?

Dr. Jeff Maltzman
We'll keep that in mind. We appreciate all your hard work very much. We'll try to go easy on you. Thanks a lot.

Dr. Eileen Moynihan
Thank you. All right.

Am I going to move on to Botox now or are we going back to any speakers, team?

Krista Babbitt
You can go on to Botox.

Dr. Eileen Moynihan
Okay, thank you.

So, Botulinum toxin injections is our next LCD for this meeting.

We had, as contractors, received some complaints from people that all of the contractors had slightly different LCDs on using these products, different frequencies, different doses, maybe different covered indications, and if you were unlucky enough to be close to another border state, the coverage could be very different from one territory to another.

So, in an effort to respond to some of those complaints, a collaborative work group was formed to deal with botulinum toxin injections, and that is what we are considering today.

So, we'll move on to the first speaker, Dr. Stuart Seiff.

Dr. Stuart Seiff
Thank you very much.

Good afternoon, everybody.

My name is Stuart Seiff from San Francisco, and I'm speaking on behalf of the American Academy of Ophthalmology, the American Society of Ophthalmic Plastic and Reconstructive Surgery, and the North American Neuroophthalmology Society.

And thank you for this invitation.

It seems that within Noridian, and it looks like we have a little bit of discrepancy in exactly what the LCD number is, so I think we'll have to sort that out, but that's probably the least of our problems. But I'm gonna be speaking on botulinum toxin injections, specifically regarding the portion addressing benign essential blepharospasm.

Next slide, please.

I have, my disclosures are here. They're not relevant.

Next slide here.

So, let's talk about blepharospasm.

It's the abnormal involuntary contraction of eyelid and periocular muscles, specifically the orbicularis muscle, procerus muscle, corrugator muscle, and actually nasalis muscle, and this is a lifetime condition requiring ongoing treatment. It's not a one-shot deal, so to speak.

The contractions typically progress from mild, such as increased blinking, to forceful and frequent squeezing of the lids, disabling the patient because they can't see and this will frequently progress, as noted in the LCD, to oral, facial, sometimes cervical dystonia, otherwise known as Meij syndrome, and these contractions spasms interfere with activities of daily living specifically, usually driving and reading.

Botulinum toxin is the first line standard of care drug for over 40 years, really without variation there, and it's because of that length of time that we really don't have many recent clinical trials for this indication, but the treatment has been quite effective.

Clinical guidelines do exist though for current dosing of these injections and given this widespread clinical standard of care; it would be unethical to deprive patients of existing medical coverage.

I also wanna just make a little statement that I feel that Noridian has done a very good job as our local Medicare carrier over the years and has, in my experience, been very responsive to the needs of my patients and your beneficiaries.

The current Noridian LCD for Botulinum Toxin use in blepharospasm actually works to get patients the treatment they need in a cost-effective fashion, and as we move forward, I really encourage Noridian to think, if it ain't broke, do we really need to fix it?

That said, in reference to the introductory remarks that I appreciate, I further want to state that much of the material in this proposed LCD is not new and has been applied by several MACs around the country over the past three years, which we have been actively, our organizations have actively been objecting to. And I can tell you that from a physician and a patient perspective, this proposal has been basically a disaster.

I hope that my comments today will help Noridian avoid this pain.

Next slide, please.

So, what we see here is a comparison of the botulinum toxin, the Botox label dating back to 1989 in the proposed LCD, and they're quite similar. But this language in the package label dates back to 1989, and this was a different era and treatment has evolved.

Further, the LCD did not even get the language from the label right as it got transposed into the proposed LCD in terms of the total dose per affected eye, and therefore, I think we need to revisit this section for sure.

Next slide, please.

Further, FDA labels do not nor were they expected to reflect actual clinical practice.

There are various reasons to be concerned with this application of Botox's FDA label.

Using an FDA label is an unconventional approach to medical coverage policy, as FDA package inserts are not intended to be absolute treatment guidelines. These criteria also overlook the FDA dosing guidelines for a competing drug, Zomen, and both labels present dosing recommendations, not strict limits as represented within this LCD.

Clinical practice for treatment of blepharospasm has significantly evolved since this label was created in 1989, and using those criteria as coverage guidelines would arbitrarily limit and deny care, allowing for disease progression, which is otherwise easily preventable.

We appreciate the LCD's acknowledgement of off-label use, but considering how common such approaches to treatment are, requiring the submission of multiple published studies is incredibly burdensome and will block proper care.

The draft policy, next slide, please.

The draft policy would create patient access safety issues and rather than going through this, let me just share with you a patient and I saw this week in my practice.

She's a 74-year-old woman who has had blepharospasm for 20 years. She actually was a patient of Alan Scott, who is the actually inventor of Botox, and he treated her conservatively for years, increasing her dosage and injection sites as needed.

I assumed her care after the unfortunate death of Dr. Scott, and at that point, the patient was receiving 20 units per side to control her spasms. And obviously this exceeds the limitation that the LCD would place on treatment.

But even at the 20 units, we were not able to give her a full 90 days of treatment interval as prescribed by Medicare because she was getting spasms two months in and having one month that she was unable to open her eyes and drive. So, I recently increased her dose to 25 units, and in doing that, she was able to reduce her undriving time to just two weeks before the next injection session.

Again, still not terribly functional, not a good result, so I am going to be changing her to Zomen at her next treatment interval, but the bottom line is that under the under the proposed LCD this woman would have been totally disabled years ago had we not been able to adjust her dosage and treatment according to her needs.

Next slide please.

So, what does the ophthalmology community suggest in terms of recommendations to modify this proposed LCD.

Next slide, please.

Any finalized blepharospasm policy should support the current effective standard of care.

With regard to placement of the injections, most papers which contributed to the FDA approval of Botox included injections to all of the protractors, that is the closers of the eyelids, including the orbicularis and the procerus corrugator and nasalis. The dosage, while it is true that increasing doses greater than five units per injection site has not been shown to increase effectiveness, many patients need six or more injections per eye depending on the manifestations of the disease, this may total 30 units per eye or 60 units' total.

Effective coverage policy should not limit treatment to less than this standard of care.

Next slide please.

As proposed, this LCD would at best disrupt current clinical best practice.

An effective policy would allow flexibility for treating physicians to exercise discretion.

This is clinically necessary given that physicians must continuously adjust the treatment based on clinical response to the prior injection session. As patients' response-

Taylor Canova
One minute remaining.

Dr. Stuart Seiff
Thank you.

As patients' response to a given drug changes over time and effective policy must support the treatment option of replacing an initial drug with another FDA approved product and this is the widely accepted standard of care for blepharospasm.

Next slide.

The American Academy of Ophthalmology does have such proposed standards in their publications, and we will be happy to share this information with you.

Next slide, please.

This proposed LCD and other publications have suggested the benign essential blepharospasm as a form for us with orafacial dystonia, and many blepharospasm patients will progress to this as the patient I presented earlier is beginning to do.

Within the LCD, the proposed management for orafacial dystonia is an example of a guideline which offers physicians reasonable flexibility to assess and specifically address patients' needs.

Given that blepharospasm and dystonia...

Taylor Canova
Thank you for your comment, but your time is up, and your line is being muted.

Thank you.

Dr. Eileen Moynihan
Next, we'll hear from Eric Busby.

Eric Busby
Hi, I want to confirm that you guys can hear me.

Dr. Eileen Moynihan
Yes, I can.

Eric Busby
Sure, thank you. My name is Eric Busby.

On behalf of AbbVie, the patients that we serve as the manufacturer of Botox, in which you will also hear me call onabotulinum toxin A or onabot A throughout this presentation, I want to thank the committee members here for the opportunity to speak to this draft policy on botulinum toxins.

Next slide, please.

I will first go through my disclosure. I am a full-time employee of AbbVie.

I am an Associate Scientific Director, Medical Peer Strategy, and I'm also a shareholder.

Next slide, please.

So, I will be covering a lot of information in this presentation, I will do my best to bucket many of our comments. Just note that AbbVie will be submitting detailed written comments, including PDFs per process. So, throughout this presentation, I will be providing key takeaways per slide.

Next slide, please.

So, to orient you to these slides, anywhere that we have highlighted something from the draft policy, we have respectfully asked for revisions, given information, other evidence that is available. So, information that you see in the blue boxes gives you an idea of what we are requesting, so slides four through eight will cover some of the key areas of focus on education of coverage, starting with chronic migraine.

So, for migraine, we are respectfully requesting the removal requiring a two-month trial of pharmacological therapies before the use of onabotulinum toxin A, and this request is alignment with the most recent AHS guidelines update.

Also, some of the products that are listed in the proposed policy are not indicated by the FDA for migraine.

For statement number eight, the language here is unclear as written and we do seek to understand likely what the language is suggesting to occur in relation to combination therapy, so we are requesting that the verbiage be revised and be considered to ensure that patients that are suffering from chronic migraine receives the appropriate care.

Next slide, please.

So, with regards to spasticity, the items that you see highlighted above, we're requesting to remove moderate to severe. This is misaligned to current guidelines, as well as the FDA approved indications for both adult and pediatric and spasticity patients.

Next slide, please.

For cervical dystonia, we are requesting that the policy be revised given the following, that the AAN guidelines do not state routine assessments utilizing objective measurements.

Onabot A is approved broadly to treat cervical dystonia that's associated with neck pain.

Next slide, please.

For Neurogenic Detrusor Overactivity, we are requesting that the moderate to severe statement for NDO is removed from current policy as it is not aligned to the FDA approved label, nor is that a statement suggested in the clinical guidance and the new AUA SUFU guidelines for NDO.

Next slide, please.

So, for OAB, we are requesting the following:

One, that moderate to severe and objective assessments are removed, and two, eliminate the need for conservative and pharmacological management before onaboutulinum toxin A therapy.

So, in the most recent updated OAB guidelines, it states that clinicians may offer patients minimally invasive therapies, such as onabot A, without requiring trials of behavioral, non-invasive, or pharmacological management. Furthermore, the guidelines acknowledge a potential association between anticholinergics and the risk of dementia.

Next slide, please.

So here we are respectfully requesting for a revision to the definition of spasticity. So, there was a recent update to this definition, and this information can be found in the 2024 AAPM&R Consensus Guidance on Spasticity Assessment and Management.

Next slide, please.

So, for muscle selection in cervical dystonia, we are requesting that the policy revises the statement to expand to any of the approved muscles for onabot in cervical dystonia, noting that the highlighted muscles here are only some of the approved muscles for cervical dystonia.

Next slide, please.

So, for spasticity, we have noted that the maximum cumulative dose of 360 units, this is a historical dose and so the latest cumulative dose for onabot A in spasticity is 400 units that is related to adult lower limb spasticity that was approved by the FDA in 2016.

We will also be providing the committee studies that show that doses of 600 units of onabot A is safe and efficacious in patients with adult lower limb spasticity.

Next slide, please.

So, furthermore, for spasticity, we've noticed that some of the other approved botulinum toxins had pediatric dosing that was mentioned, and so, AbbVie would like to respectfully request that onabot A is also approved for pediatric spasticity aged two years or older, and that the dosing information for pediatric upper and lower limb spasticity are included into this policy.

Next slide, please.

So, for this slide and the next slide, which addresses NDO and OAB, we will be providing additional details, including our phase two, phase three data that supports higher dosing for those patients who are not achieving efficacy from the typical on-label dosing.

So, please go to two slides. Go two slides.

All right.

So, here for blepharospasm, I'm not going to spend time on here. I will say that we are aligned to Dr. Seiff's presentation on the information that was presented on blepharospasm.

Next slide.

So here there's limitations in the use of guidance or technology, so we are respectfully requesting that guidance technology such as ultrasound is included, and we will be submitting additional data on this.

Next slide, please.

So lastly, there are many ICD-10 codes from the prior policy that has been removed or omitted for reasons that's unknown to this draft policy, so we will be providing a comprehensive list of these codes with supporting literature, and we're requesting that these codes are added into the final policy.

Next slide.

So, I just want to thank you all for my time to comment on this draft LCD.

Thank you.

Dr. Eileen Moynihan
Thank you for your time.

Dr. Amandeep Mann, you have the floor.

Dr. Amandeep Mann
Hi there, just wanted to make sure everyone can hear me.

Dr. Eileen Moynihan
Yes, we can.

Dr. Amandeep Mann
Perfect.

Good afternoon, everyone. I'm Amandeep Mann and I am representing Ipsen Biopharmaceuticals, the manufacturer of Dysport or abobotulinum neurotoxin, which I'll be referring to as ABO or abobot A throughout the presentation.

Next slide, please.

Just a disclosure, I am a full-time employee of Ipsen and hold shares of Ipsen stock.

Next slide.

A disclaimer before I start presenting, this presentation is in response to MAC requests for feedback on the updated MAC draft LCD policy consistent with approved, FDA approved as well as off-label uses of bot As for the Medicare population.

Ipsen Biopharmaceuticals does want to recognize and thank Noridian as well as the CMS members for efforts in updating this very comprehensive BoNT LCD policy.

For this presentation, I'll be walking through some key sections of the draft policy that we are hoping can be updated to improve access of care to the Medicare population and select sections will be called out within the coverage for AboBoNT-A .

I do recommend everyone to refer, I do refer you to the ABO prescribing information for complete details on the box warning for distance spread of toxin effect contraindication warning precautions and adverse reactions.

Just as everyone else has mentioned, Ipsen will be submitting a detailed response letter including relevant supporting references for the content I will be presenting and hopefully you can read through the fine details and consider those changes for the final LCD policy.

Next slide, please.

ABO for Therapeutics or abobot A is FDA approved for the treatment of cervical dystonia in adults, and this was approved in 2009 and also is approved for treatment of spasticity in patients of two years of age and older.

Next slide.

Just providing some historical context to abobotulinum neurotoxin, it was actually developed in the 1980s and was first approved for the use for hemifacial and blepharospasms in 1990, so ABO has been marketed for over 30 years globally across multiple indications, including but not limited to cervical dystonia, so it has had a historical presence globally.

Next slide, please.

So, the first request here is to update the indications of coverage to be inclusive of all CD and spasticity patients that can benefit from the treatment of botulinum neurotoxin. And this is really to avoid restricting access to only moderate or severe patients.

The support is provided with the bullet points below, but just to clearly lay out, the AboBoNT-A FDA approved label is not limited by disease severity for either indications of cervical dystonia or adult spasticity.

Also, the American Academy of Neurology, the guidelines recommend AboBoNT-A as the only BoNT-A that has the level A recommendation for use in the treatment of cervical dystonia and adult spasticity, including both upper limb and lower limb. And the treatment guidelines really do not restrict the use of BoNT-As by the severity of the disease, so this is for both cervical dystonia and adult spasticity.

The third support is from the American Academy of PM&Rs.

A consensus guidance, which was just recently published, also does not restrict or categorize the use of BoNT-A treatment within adult spasticity based on severity of the disease.

Next slide, please.

The second request is to reinstate the on-label diagnosis codes that are part of the original LCD policy that are now no longer on the draft policy, and this is including cerebral palsy, all paralysis and collegiate classification, contractors and muscle spasms.

So, based on the safety and the efficacy data provided through phase 3 registrational trials, we were able to get a broad indication for both spasticity and/or spasticity to not be inclusive of paralysis classification and or etiology.

We also have phase 4 studies that are reflective of real-world uses of ABO within the US and globally in varying populations of limb paralysis.

Furthermore, we have pediatric spasticity where we showed the safety and efficacy of ABO and upper and lower limb spasticity and that was evaluated in cerebral palsy patients.

Of note, the types of paralysis and spasticity adult or pediatrics, the patients can be classified as diplegia, hemiplegia, paraplegia or quadriplegia, according to the area of the body that is affected and therefore, we request these codes to be reinstated for the treatment of abobotulinum neurotoxin.

Next slide, please.

The third request is to update the CPT code title, spastic hemiplegia, to spasticity in group 14, and this is in the current LCD policy for AboBoNT-A. The current draft LCD policy title is highly limiting and may unduly restrict treatment of other types of spasticity in the Medicare population.

And this really just aligns to the same support that I just provided in the slide before, where the FDA approved usage of abobotulinum neurotoxin is not restricted by etiology or severity or the type of presentation of the spasticity, so changing that title from spastic hemiplegia to spasticity would be greatly appreciated, and also we have phase four studies in adults, as well as pediatrics studies that support the use of toxin, abobotulinum specifically, in CP patients that are categorized within different types of paralysis.

Next slide, please.

The fourth request was to include, I believe we might have, can we go to the next slide?

Next. Next, there we go.

So, the fourth request is to include all ABO on-label muscles, specifically for cervical dystonia, which are FDA approved for treatment with abobotulinum neurotoxin, and they're bolded and indicated there in the first bullet.

We would also like an updated language for the dosing for abobotulinum neurotoxin to include both the ALL and PUL approved dosing, which is in our label and that's specifically highlighted in the red boxes down below in the table.

So that's maximum dose of 1500 units for adult lower limbs spasticity and the maximum unit of 640 units for pediatric upper limbs spasticity with 16 units per kg as also the max dose, whichever one is lower.

Next slide, please.

The fifth request is to include, similar to the previous presentation, we would also like to support the inclusion of the ultrasound CPT code, image guidance, and the treatment of spasticity and cervical dystonia.

In our abobotulinum neurotoxin, FDA approved PI, the guidance technique is recommended as you're treating patients with cervical dystonia or spasticity. There is also published literature that indicates the guidance techniques may mitigate adverse events by helping to visualize the target injection sites.

In addition, we have our recent publication, recent data from a phase four study in adult lower limb spasticity with the treatment of ABO where we showed that patients that were treated with ABO using ultrasound actually had a better patient goal attainment than those patients that were treated without ultrasound guidance.

And the next slide, please.

The sixth request is around the reinstatement of ICD-10 codes for abobotulinum neurotoxin that are in the current policy, including other dystonia's, and also would like to provide support to consider additional codes for abobotulinum neurotoxin within the new policy.

So, as I mentioned earlier in the presentation, one of the first indications that was approved for AboboNT-A in Europe was blepharospasm and hemifacial spasms in 1990s.

We also would like to bring awareness to the existing published data on ABO use and other conditions that fit under other dystonias, including but not limited to blepharospasm and hemifacial spasm.

Taylor Canova
One minute remaining.

Dr. Amandeep Mann
Thank you.

There are also data that support ABO use in other conditions, such as neurogenic detrusion overactivity, migraine, and hyperhidrosis, which are also indications approved outside the U.S.

I do refer you to review our Ipsen comprehensive written comment response that will be provided along with supportive references for additional details.

Next slide, please.

This really just summarizes all the changes that we're requesting, and at this point, I just want to thank you everyone for giving me the opportunity to speak on behalf of Ipsen biopharmaceuticals at this forum and we look forward to submitting our written response along with the supporting ABO data and the PI for your review. And I hope you consider our suggestions in relation to ABO coverage for the final policy so that Medicare patients that are suffering from spasticity and dystonias can be managed with appropriate treatment and have options to manage their chronic and debilitating conditions.

Thank you.

Dr. Eileen Moynihan
Thank you.

And now Judith Gutch.

Krista Babbitt
Not seeing her.

Taylor Canova
She was on it. Yeah, I just don't see her anymore.

Krista Babbitt
We can then move on to Jane Boyd.

Jane Boyd
Hello, I'm here.

Krista Babbitt
She didn't have any slides.

Dr. Eileen Moynihan
Okay, all right, thanks, proceed.

Jane Boyd
Can you hear me?

Dr. Eileen Moynihan
Yes.

Yes. Go ahead.

Jane Boyd
Okay thank you for the opportunity to speak to you about the proposed botulinum treatment guidelines for blepharospasm.

I want to echo the issues raised by Dr. Seiff, I do not feel that the proposal as written reflects current treatment practice.

I'm a physician, but my specialty is internal medicine, and I myself developed blepharospasm at the age of 55, and I've been dealing with its effects for the past 10 years.

I volunteer for the Benign Essential Blepharospasm Research Foundation, and I served on the executive committee for over three years.

This is a rare condition, affecting about 1 in 10,000 patients.

During my career in primary care, I only saw one patient with blepharospasm, and she had already been diagnosed when she became my patient. However, in my work with the Blepharospasm Foundation, I've seen and spoken with many other blepharospasm patients and treating physicians.

I want to emphasize how disabling this condition can be. Some healthcare professionals confuse it with myocomia, the transient twitching that can affect the eyelids due to stress or excessive caffeine, but blepharospasm, in contrast, affects the greater orbicularis oculi muscle.

This large muscle is present in the eyelids and a large bullseye-shaped distribution surrounding the eye, blepharospasm causes involuntary contractions and closes the eyes. Some of us are functionally blind.

Sorry?

Dr. Eileen Moynihan
Can I ask everyone who's not speaking to be on mute, please?

Go ahead.

Sorry about that.

Jane Boyd
Okay.

No problem.

Without adequate treatment, I can't stop blinking and my eyes can involuntarily clamp shut, it's one of the reasons I retired at age 55. It's taken several years for my doctors to identify the optimal dose and injection pattern for me.

In speaking with other patients, I find this is not an unusual scenario. This is not a one-size-fits-all condition, and treatment needs to be individualized.

In the course of my treatment, I've seen seven different injecting physicians, some were neuro-ophthalmologists, some were oculoplastic surgeons, all were quite familiar with blepharospasm in its treatment.

I would like to share some of the details of my treatment to highlight the issues in the proposal that are concerning for our community.

There are three areas I'd like to bring to your attention.

The first is limiting the number of injection sites to three per eye. My first injector began with five sites per eye. This provided me limited relief despite an increase in dosage over the next few visits, so I sought a second opinion. My second injector increased the dosage again and the number of injection sites to 21, including injection sites in my eyelids.

I got significantly improved results.

My subsequent injectors have used between 21 and 26 injection sites.

There was a survey done in 2016 published in the Ophthalmic Plastic Reconstructive Surgery Journal, and the doctors who were surveyed used an average of 14 sites.

The second issue is limiting the initial dosage to 7.5 units per eye, a total of 15 units, and subsequent doses to twofold, or 30 units' total.

Your document also states, quote, "no more than five units per affected eye", which I think is perhaps a mistake, I think you meant five units per site, but despite that, my first injector gave me 32 units for my first treatment, and over the course of subsequent injections, rapidly increased to 50 units. I've had up to 100 units per treatment, however, if the proper sites are chosen, and my ideal dose seems to be between 50 and 60, all of my injectors, besides the initial one, have used a minimum of 40 units.

The third issue is limiting treatment to every 12 weeks.

I, like other patients, feel my injections wearing off at about eight weeks, but wait to get my injections every 10 weeks.

There's significant variability in the length of time botulinum is effective for different individuals.

Your references 87 and 89 in your proposal document acknowledge this variability.

Reference number 87 states the mean duration of effects was about 10.6 weeks, and reference 89 states average response time is 6 to 12 weeks. Because it takes about a week for the botulinum injections to become effective, if I were to receive injections every 12 weeks, there would be three weeks, each injection cycle where I would significantly be disabled.

The safety of shorter injection cycles has been studied. A paper published in 2016 by Jankovic and others demonstrated that injection intervals ranging from 6 to 20 weeks had no impact on the incidence of adverse events but resulted in better patient satisfaction and lower scores on the disability index. No subject developed neutralizing antibodies.

Please reconsider the limitations you are placing on botulinum toxin injection site number, dosage, and frequency. Physicians need to be empowered to individualize and optimize treatment for this very disabling condition.

Papers in the medical literature support this approach and I will be submitting papers to you.

Thank you.

Dr. Eileen Moynihan
Thank you very much, and thanks for your time.

Are we able to see if Judith Gooch is on?

Krista Babbitt
I don't.

Dr. Eileen Moynihan
Okay, still not on?

Krista Babbitt
Dr. Min is on, I just need to find his presentation.

Dr. Eileen Moynihan
Okay, that's for a different topic, right?

Krista Babbitt
Correct. That's for back to AI. Okay.

So, Dr. Min, can you unmute yourself?

Dr. James Min
Can you hear me now?

Krista Babbitt
Yes, we can.

Dr. James Min
Okay, great. Thank you to Dr. White and Moynihan and especially Kari for helping me out with my technical difficulties today and very much for still allowing me the opportunity to speak in this open meeting today.

Just by way of introduction, my name is James Min, and I'm a clinical cardiologist. I've devoted my career to the study and prevention of coronary heart disease as a clinical trialist and as an advanced non-invasive imager to improve our understanding of coronary artery disease, which tragically remains the number one cause of death in this country.

I previously served as professor of medicine and radiology at the Weill Cornell Medical College and the Director of the Dalio Institute of Cardiovascular Imaging at New York Presbyterian Hospital.

And then germane to this discussion, I was the founder of a clinical program called Heart Health that we established in 2013, which was a precision heart care clinical program that served as our foundational experience for the AI-QCT technology and discussion today that allows for advanced atherosclerotic plaque analysis.

For full disclosure, I currently serve as the founder, CEO and an employee of Cleerly, which offers the AI-QCT technology that I've found to be so valuable in my clinical practice, having taken care of thousands of patients.

I just wanna thank the medical directors of Noridian on behalf of our company for their thoughtfulness for the proposed coverage determination of AI-QCT, which will allow for the performance of advanced plaque analysis from non-invasive CT scans in select individuals, and we look very much forward to the opportunity to witness the application of AI-QCT in clinical practice and favorably affecting the lives of patients with coronary artery disease, a task that cannot currently be done by routine physician CT evaluation.

Our only encouragement to you would be to allow for the performance of AI-QCT in two additional subsets of symptomatic patients who undergo CT, which we believe to have been unintentionally omitted in the current proposed coverage determination based on the proven clinical evidence and the Professional Societal Guideline recommendations. And those two additional subsets would comprise patients with stable chest pain for whom the preponderance of clinical data exists, and patients who meet the CAD-RADS-1 criteria, which is the one to 24% stenosis for whom more than 40% of the heart attacks actually occur in that group.

So let me try to provide you with a rationale for these two requests.

So, this slide here demonstrates a coronary CT angiogram on the left and the right. In the middle is the invasive angiogram that we've historically used.

In the past 50 years in cardiology, there's been only one non-invasive test that has ever demonstrated within the context of a well-performed randomized trial to actually favorably influence patient management to improve patient hard, hard patient outcomes in symptomatic patients without known, but with suspected coronary disease, and that is the coronary CT angiogram.

As you can see from the bottom left, the non-invasive CT scan is rapid, safe, and based upon its benefit to improving patient lives, has now achieved the sole level 1A indication in the HA and ACC guidelines for evaluation of both patients with stable as well as acute chest pain who present with suspected coronary disease.

In the two figures on the right, those actually represent the same patient, the invasive angiogram in the middle, that bookmarked area with the yellow lines demonstrates no significant stenosis or blockages, on the right, the noninvasive CT of that same patient similarly demonstrates no significant blockages, but what you can see is that if you do an advanced plaque analysis, that yellow highlighted area shows clearly that the patient possesses very, very severe disease in his artery.

This lesion is often referred to as a widow maker lesion for good reason, but which is missed by conventional testing and stenosis severity alone.

If you can advance to the next slide, as we said, that CT is the only test that has ever been demonstrated to improve patient outcomes in a large-scale randomized trial. If you start to understand, and this was the SCOT Heart trial, for clarity, where they compared to historical care using stress testing versus CT-guided care and you can see in the left Kaplan-Meier curves that that reduced heart attacks and deaths by more than 40%.

If you look to the right, upon deeper examination of the reasons that drove those improved outcomes in patients undergoing CT, you can see that as compared to standard of care, there were no differences in the CT arm for rates of cap, invasive angiography, stents, PCI, bypass surgery, cabbage. Indeed, the only difference in patients who underwent CT versus historical methods of evaluation was significant increased utilization of preventive medical therapy.

So, if you look to the, go to the next slide, beyond the SCOT Heart study, the totality of clinical evidence over the last 20 years demonstrates at least four actionable patient-centric findings that can be derived from advanced plaque analysis.

The first is risk, right?

So, plaque, and particularly a phenotype called low attenuation plaque, is the strongest predictor of who will have a heart attack and who will not in the future.

This was not only found in the SCOT Heart trial, but as well as trials performed by our investigative group in the PROMISE trial that comprised more than 10,000 patients and the ICONiC study which comprised more than 25,000 patients with long-term follow-up.

Further, the field has demonstrated that not all plaques are the same, and that is very, very important for patient management as the phenotypic appearance of a plaque will strongly drive the patient-centered risk and influence our clinical decision-making. And simply stated, it's the non-calcified plaques that are the very high-risk plaques, while the calcified plaques are stable and even associated with lower rates of heart attacks.

These findings allow us to move to number two, which is to guide medical therapy in a personalized and an effective manner, as we have done and determined through clinical studies that have shown that improvements in lifestyle and intensification of medical therapy on a personalized level do less to make plaque go away, but more often to transform plaque from that non-calcified to that calcified phenotype as a mechanism of stabilization.

So, you can imagine that in symptomatic patients who present with suspected coronary disease, advanced plaque analysis offers us a unique opportunity to identify patients with residual risk, i.e. those who would benefit from more intensive medical therapy and lifestyle changes.

Plaque analysis can also help us promote precision heart care for invasive procedures as evidenced by the third and fourth bullets, i.e. getting the right patients to the cath lab whose symptoms are due to coronary artery disease and effectively avoiding unnecessary invasive procedures in patients who can be treated safely with conservative medical therapy rather than the invasive therapies.

Evidence has shown that advanced plaque analysis allows us to pinpoint the patients who will benefit from these choices in a manner that is effective, independent, and incremental to all of our prior corner disease measures.

If you go to the next slide, it's because of this wealth of evidence that the most recent American Heart Association and American College of Cardiology chest pain guidelines in 2021 made several recommendations for the first time that encourage the use of plaque analysis in patients with acute chest pain as well as stable chest pain.

I would point you to the stable chest pain indication in blue in the fourth bullet, which highlights that these stable patients with nonobstructive coronary disease would significantly benefit from plaque analysis to guide therapeutic decision making.

Notably, that definition of nonobstructive in the American Heart Association guidelines is inclusive of those with a maximum one to 24% stenosis or CAD-RADS-1, and it's that group actually that experiences more than 40% of the heart attacks and are missed by conventional measures that we've used in the past.

If you go to the next slide, it's not only the American Heart Association and the American College of Cardiology, but of equal import, the Professional Radiology Governing Society, the American College of Radiology, also recommends advanced plaque analysis for patients with both acute as well as stable chest pain and also recommends that for patients with CAD-RADS-1, which is defined by the guidelines as a 1 to 24 percent stenosis.

Over in the bottom right, you can see that in contradistinction to the AHA guidelines, the ACR guidelines also recommend advanced plaque analysis for those with higher stenosis than greater than 70 percent.

Taylor Canova
One minute remaining.

Dr. James Min
Thank you.

For this distinction between our professional governing bodies and we as a company do not actually believe that plaque analysis offers that much incremental value in the greater than 70% stenosis, as we generally think of those patients as sick and offer them maximal medical and invasive therapies, but that is what the multi-societal guidelines had recommended.

And on the last slide, if you can advance, in summary, the evaluation of plaque now is now widely considered as the standard of care by AHA, ACC and ACR respectively, but it cannot performed manually.

In our research studies, these analyses took up to 10 hours per patient, and the accuracy was not what it could be with powerful computational tools that allow for routine assessment of our patients.

Again, we thank the Medicare Medical Directors, this is a very fast-moving field, and your proposed positive coverage determination will allow clinical practitioners to emphasize plaque as the primary diagnostic and therapeutic target.

We would respectfully request that Noridian allow patients with stable chest pain who represent the preponderance of patients enrolled in prior clinical trials, as well as those with 1 to 24 % stenosis who comprise the majority of patients who will suffer heart attacks to be included in this coverage policy. In doing so, I think that this would be in keeping with the prior clinical evidence as well as societal guidelines.

Thank you for your time and attention today.

And again, thank you for your patience with my technical difficulties today.

Dr. Eileen Moynihan
Thank you very much.

Should we try first? Is our missing speaker on yet or not? Still, no?

Taylor Canova
I'm not seeing them on.

Dr. Eileen Moynihan
Okay.

So, I'm going to turn it over to Taylor for closing and next steps, and Taylor, you may want to mention something about using your own link when you're a speaker.

Taylor Canova
Yes, in the future and for this meeting, you would have to use your own link to connect as it's individual to you, and if you connect via someone else's link, we will not be able to identify you.

In closing, we would like to communicate the next steps in the policy development process.

The comment period for the proposed LCDs will remain open until July 13, 2024. All comments to be considered by our medical directors for the proposed LCDs must be submitted in writing.

Written comments can be emailed to policydraft@noridian.com or mailed to the address on your screen.

Comment information for our proposed LCDs are located on our website at noridianmedicare.com.

Upon review of the comments, our medical directors will either finalize or retire the proposed LCDs.

Responses to comments will be viewable in the response to comments article.

Please monitor our website or register for listserv notifications to be informed of actions taken on our proposed LCDs.

Do any of the CMDs have anything that they would like to say before we end this meeting?

Dr. Barry Whites
I want to thank everybody for a very thorough review of information and certainly appreciate it. It's nice to have involvement and we do appreciate it. Thank you so much.

Taylor Canova
Great, thank you so much.

This concludes our meeting.

Thank you for attending the Noridian Open Public Meeting.