MolDX: Molecular Biomarker Testing to Guide Targeted Therapy Selection in Rheumatoid Arthritis Open Public Meeting - October 20, 2022 - JE Part A

Jocelyn Fernandez:
Good afternoon, everyone. My name is Jocelyn Fernandez, I am one of the Medical Policy Specialists here at Noridian Healthcare Solutions.

Before we begin, I'd like to make the following announcements.

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In addition to 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. Anitra Graves

Dr. Graves, you may begin.

Dr. Anitra Graves:
Thank you, Jocelyn.

Good afternoon. Welcome, everyone, to the Noridian Virtual Open Public Meeting. My name is Dr. Anitra Graves.

I am a Contractor Medical Director with Noridian Healthcare Solutions representing Medicare AB; Jurisdictions JE and JF.

We are looking forward to your comments and are very appreciative of the time you've committed to preparing them.

Today, we are discussing LCD JE-DL39467 and JF-DL39469. MolDX: Molecular Biomarker Testing to Guide Targeted Therapy Selection in Rheumatoid Arthritis.

This is a stakeholder initiated new LCD request from Jerry Harashima, representing Scipher Medicine. Documentation of the original request is posted online on the Medicare Coverage Database and can be located in the accompanying tracking sheet, which will appear upon searching for this specific LCD ID number.

This is a draft policy that is a non-coverage policy, and we have two presenters today.

The first presenter, Dr. Nehad Solomon with Arizona Arthritis and Rheumatology and Research Center.

Jocelyn Fernandez:
Dr. Solomon, your line is open.

Dr. Nehad Solomon:
Hello, everyone. I'm Dr. Nehad Solomon. I am the Medical Director at Arizona Arthritis Rheumatology, research arm. I'm also one of the managing members of our clinical practice.

Can you advance the slides, please?

This is a picture of me, young and robust, and I’ve lost a little bit more hair since this picture. But as I mentioned, I've been serving the Phoenix metro area now for the past 17 years, actively engaged in clinical research trials for many rheumatic diseases, including biomarker testing, as what we're discussing today.

I serve on the Phoenix Rheumatology Association Board, and I was the past President currently the Vice President also serve the COIN Committee part of the American College of Rheumatology and soon to be on the board of the American College of Rheumatology.

Next slide, please.

So, as we know, rheumatoid arthritis is in dire need of precision medicine tools in order to help guide therapy selection.

Rheumatoid arthritis is not homogeneous, but rather, heterogeneous, and many patients respond to medications that we currently have and yet many do not. Sequentially, at this point, we choose medications without any real guide, unfortunately, many things lead to use of drugs based on formulary restrictions and yet there's still nothing out there to guide the selection of a biological or targeted synthetic DMARD. PrismRA testing grants us some insight to the patient specific biology. Patients and rheumatologists are in dire need of precision medicine tools such as the PrismRA test.

This way, this tool helps select drugs based on the patient's specific disease biology and helps us identify whether or not they may be responders to various medications. Currently, we choose medications on the basis of which one came out first, which one may be less expensive to the society, and which one may be preferred on a formulary. But it really has no bearing on whether or not the patient will respond to it.

We oftentimes refer to ACR guidelines but being part of the ACR and various board committees, these guidelines could take anywhere from 5 to 8 years to update and unfortunately, we don't have time to wait for guidelines to continue to be updated. Although we constantly look and push at the end of the day, we need to practice medicine in the year 2022 and move forward.

Even the selection of the first line biologic that is not suited for patients’ biology will dramatically impact outcomes in disease progression.

For example, if we choose the wrong drug, we've wasted critical time where you have an advancement of disease. Potentially erosive disease, destruction, and disability, which is happening as we're waiting 3 to 6 months for a therapy to work.

That's why this therapy is really a novel breakthrough. It would be a shame, not have this as a tool. I was involved in the clinical trials. We saw firsthand, dramatic gains by utilizing this test. Currently, using this test in clinical practice, it is helping us get it right, before wasting precious time.

Next slide, please.

So, I'd like to share with you a case study. Everything here is obviously deidentified. This is a 67-year-old patient of mine who has zero positive rheumatoid arthritis, also overlap with Sjogren’s syndrome in osteoporosis. She's had RA since 2003, so nearly 20 years. She'd been treated with a variety of traditional DMARDs, such as sulfasalazine methotrexate and then conventional biologics as they came to be, Enbrel Humira and Remicade in the earlier part of the century.

In 2020, because the formulary requirements despite the fact that she had already been on three different TNFs, she was, we were asked to use Simponi SQ which, yet another TNFi and the results were equivocal. Are initial response lasted for a few months, and then the response was lost.

Unfortunately, because of formulary requests, insurances dictated repeated TNF trials, even though, clinically we knew. And after usually two TNFi’s, you're not going to get a response thereafter.

Subsequently, as PrismRA became available, we ordered this test on the patient only to find out that her score was 11.1, which was a high likelihood of non-response, had we had this information earlier on in her treatment course we would have saved precious time.

She was subsequently switched with this knowledge to a different mechanism of action, Orencia, which is a CTLA4-Ig inhibitor and is now doing much better.

Her disease activity marker, the CDAI, before the switch was at 22, which is moderate disease activity and after six months of Orencia, it was down to 5, which is low disease activity.

And so ultimately when we look at this type of patient, when we look at our patients in the clinic, Those patients who were exposed to a TNFi or even a second TNFi are losing not only precious time, but their biology is changing, and so if we can get it right, get the medication right sooner by utilizing the PrismRA test, we can avoid all of that. It would be a shame not to have this tool, which is a breakthrough in modern medicine to help sort of turn the lights on in this very nebulous space that we operate on and help us get it right for our patients, and save them from disability, and also save society from the additional cost.

Next slide, please.

These are the references looking at a variety of the things that I've mentioned, forementioned, in this presentation. I ask you to reconsider your stance and make this an available tool that is covered. It is a one and done. It is not something we're going to continue to order over and over again and as this tool continues to evolve, I think it will be an invaluable tool that will be part of our mainstay of treatment algorithms. I thank you for your attention today.

Dr. Anitra Graves:
Thank you, Dr. Solomon, and my apologies for butchering your first name.

Our second presenter is Jennifer Dines, she is the Vice President of Regulatory and Medical Affairs with Scipher Medicine, Dr. Dines.

[Inaudible 11:15 - 14.11]

Dr. Jennifer Dines:
Oh, my goodness. I’m so sorry, and we had the audio working at the beginning, and for some reason it failed. Right, when it was time. So, thank you for waiting, listening. Apologies to all for that technical difficulty.

Can I get started now?

Jocelyn Fernandez:
Yes, please.

Dr. Jennifer Dines:
Great, first slide. We at Scipher Medicine are appreciative of the opportunity to present and look forward to working with Noridian to further support our coverage application and thereby provide this vital test to Medicare beneficiaries.

Very briefly, and on the next slide, I wanted to introduce myself as it relates both to precision diagnostics and clinical coverage.

As a clinical geneticist, I have focused my career on translating novel technology to the clinic to improve patient outcomes. With my keen interest in Precision Medicine at the University of Washington, I participated in the evolution of advanced sequencing technologies, integration into medical practice, and saw an enormous impact on patient care, as it has transformed how we better treat and diagnose patients in the field of oncology.

At Adaptive Biotechnologies, I expanded from oncology to the use an autoimmune and infectious diseases, and help the company received FDA emergency use authorization, for a new class of diagnostics, the machine learning classifier base blood test to combat the COVID pandemic. And now, leading similar efforts here at Scipher Medicine, towards that end and on slide three. I will be providing a brief introduction and background to our company and PrismRA, which has continued to gain adoption by the rheumatology community in parallel with the progression of studies that demonstrate its validity and utility in the clinic.

I will conclude with the urgent need for this test.

In the next slide, our company, Scipher Medicine, is focused on providing physicians with the right tools and solutions to deliver precision-based care to their patients.

Doing so, helps achieve the critical aims of improved outcomes, lowered costs, and more efficient healthcare delivery, specifically, in the next slide, PrismRA, the test we're discussing today is already experiencing large-scale adoption across the country.

Throughout the United States, physicians, and their practices as a whole, have been ordering our test, given its utility and necessity in the care of their patients, and is used by over 600 providers across 400 practices.

Over 45% of commercial tests come from patients covered by Medicare, and as such, our goal is to work collaboratively to improve access and coverage as we're doing today.

Next slide.

This summarizes our clinical validity supporting PrismRA’s integration in the clinic.

PrismRA has been clinically validated, in both retrospective and prospective studies in over 800 patient samples and demonstrated consistent performance across multiple cohorts, with studies reporting close to 90% positive predictive value, solidifying the value proposition of this innovative test.

Most recently, in the AIMS study cohort, at the far right of the slide, we evaluate the performance characteristics of Prison MRI in 369 patients.

The resulting performance included a PPV of 88%, thereby demonstrating the continued performance in a cohort nearly three times larger than prior studies summarized on this slide.

As 90% of patients with RA are treated with the TNFi therapy as first line biologic, targeted therapy, PrismRA can accurately redirect patients with a molecular signature of TNFi, non-response to an alternative therapy increasing their likelihood of achieving targeted clinical outcomes, which I will go over in more detail, after first clarifying a misinterpretation of our clinical utility data on the next slide.

Here, we believe this to be a misinterpretation of a key result related to the utility of the test.

As was noted in the draft non-coverage decision and detailed at the bottom of the slide. The conclusion of reach was surprising to us at Scipher because an improvement over baseline and standard of care is exactly what we measured and achieved as a primary endpoint.

As scene here, on the left of the slide in table one, and highlighted, the absolute CDAI average among the predicted non responders for those receiving a TNFi and those receiving an alternative mode of action or both in the 30s. After six months and shown in the second table on the right of the slide, those predicted TNFi non-responders, only 10% of the group receiving a TNFi achieved ACR50. While those align with the test results and on an alternative mode of action, have more than three times that, with 34.8% of patients achieving ACR50.

I will now review the clinical utility data in more detail on Slide 8.

As I have discussed previously, our test has been clinically validated in over 800 patients. Now, depicted on this slide, prospectively evaluated for provider treatment selection and clinical outcomes in over 900 patient samples.

Important to note on the slide are both end values of our studies, as well as the primary endpoints achieved.

Additionally, and highlighted in the table at the bottom of the slide, we assess the patient numbers and demographics further to determine the representative value to Medicare beneficiaries.

Across the interim analyzes, 22 to 36% of participants, or 65 years of age or older, or females, represented 80 to 85% of patients, and 25 to 32% identify as nonwhite, and are Hispanic or Latino in this age group.

I will now go over steadied primary endpoints in greater detail on slide 9.

From our peer reviewed paper, which brought our value to 274 patients. That was published in June of this year one key point represented below the letter B on the figure on the left. We see those with a molecular signature of non-response treated with an alternative mode of action, had a 1.8 or greater improvement and CDAI scores and those treated with a TNFi.

Next slide.

We have submitted for publication, an additional clinical utility paper that is pending publication.

Here, we not only increase the end value of patients tested, and outcomes measure to 489 patients, but also show that treatment selection guided by our test results in 1.5 to 2.9, greater improvement in outcomes after 6 months of biological therapy initiation; compared to standard of care, external EMR derived control group or PrismRA was not used to predict therapeutic non-response TNFi therapy.

In the next slide, and in response to MolDx draft LCD, we explore how robustly our tests can predict TNFi non-response compared to clinical and serologic features in combination, or alone.

We Scipher Medicine, as well as key opinion leaders and advocacy groups are surprised to hear that the contractor believes a tools and metrics are already available to practicing physicians and let the utilization of these metrics and values would provide predictive power comparable to PrismRA.

Here, I'm sharing data from two of these analyzes, comparing clinical, serologic, and molecular features individually, and in combination.

We see that PrismRA, MSRC shaded in gray is better able to predict TNFi non-response, more robustly across these two cohorts than any other combination of clinical or serologic features.

The next slide, we summarize physician and advocacy group sediments that continue to provide support of our test and re-affirmed the dire need to incorporate PrismRA into their medical practice.

This includes two of the subject matter experts, Dr. Huffstutter and Dr. Niemer from December 7th, CAC meeting, as well as Dr. Solomon, from this call today.

This includes the devastating effects that occur as patients are traveling different therapies until they find the right treatment to control their disease.

Importantly, we know that patients who do not respond to their initial therapy are less likely to respond to subsequent therapies.

Therefore, the utilization of PrismRA will help Drs make a more informed choice and will improve patient outcomes, as demonstrated in the body of evidence we reviewed today.

Importantly, Medicare does not require TNFi as a first choice and second line therapy and PrismRA use in the clinic can be seamlessly integrated with decision impact with therapy decisions based on an individual patient you need biology.

In the final slide, I will conclude, which highlights and shifts the focus solely on the patient and their journey.

Here, we see on the left-hand side, and in gray, the patient's journey is long and arduous. Inadequate control of our results in chronic inflammation, which can lead to joint damage, permanent disability, and poor health outcomes, including shorter life expectancy.

Prior to PrismRA, management of patients with RA includes a trial-and-error approach.

Since this approach often fails to efficiently identify the most effective therapy, RA patients suffer prolonged, poorly controlled disease, irreversible joint damage, an increased risk of cardiovascular disease, cancer, and death.

As a physician myself, I fully understand the value of precision medicine tests and the need to provide coverage for them so that they can be made available to patients. With PrismRA and illustrated on the right-hand side of the slide. Patients can avoid treatment they're unlikely to respond to and start the right therapy sooner leading to improved outcomes.

We respectfully request that Noridian support PrismRA LCD for this innovative test. As such, I will now conclude our presentation. Thank you.

Dr. Anitra Graves:
Thank you, Dr. Dines. This concludes the presentation portion of today's meeting. Again, we want to thank you for taking the time to prepare your comments. We will now move on to closing and next steps.

Jocelyn Fernandez:
The comment period for the proposed LCD will remain open until November 19, 2022.

All comments to be considered by our medical directors for the proposed LCD 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 LCD's are located on our website at noridianmedicare.com

Upon review of the comments, are medical directors will either finalize or retire the proposed LCD.

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 LCD.

I will now turn the meeting back to Dr. Graves for final remarks.

Dr. Anitra Graves:
Yes, I just wanted to remind our listeners that this policy is a collaboration with permit Palmetto GBA and the MolDx program. So, as we review these comments, we will be doing so in a collaboration with those medical directors, as well, to produce a final response to comment article.

Thanks again for participating in our virtual open meeting.