Subscribe
Share
Share
Embed
Welcome to Connecting ALS. Today we discuss the latest on the effectiveness of edaravone.
Connecting ALS is a weekly podcast produced by The ALS Association in partnership with CitizenRacecar. We aim to discuss research and technology developments, highlight advocacy efforts, and share the personal stories woven through the community.
This transcript was exported on Dec 14, 2022 - view latest version here.
Dr. James Berry:
The reason to go to a commercial database like this is that it's very comprehensive. It has millions and millions of people and a lot of data about those people. It's not one commercial insurance, but broadly, lots of insurances. And so if people switch carriers in the middle, we can still follow their progression throughout the disease.
Jeremy Holden:
Hello, everyone, and welcome to Connecting ALS. I am your host, Jeremy Holden. The United States Department of Veteran Affairs has made Relyvrio available for the treatment of ALS for veterans who are living with the disease and who receive care at VA clinics or ALS specialists. This makes the VA one of the first healthcare payers or insurers to provide access to the drug. The decision comes after the ALS Association urged the VA, Medicare, and other healthcare payers to provide coverage without exclusion. We'll share links in the show notes so you can learn more about the fight for access to approved treatments. As the search for more treatments and eventually a cure for ALS continues, researchers also continue to learn more about the effectiveness of already approved treatments. I recently had the chance to catch up with Dr. James Berry, the Winthrop Family Scholar in ALS sciences, the director of the Massachusetts General Hospital Multidisciplinary ALS Clinic, and chief of the Division of ALS and Motor Neuron Diseases, to dig into some recently published evidence on the effectiveness of Edaravone in the treatment of ALS.
Dr. Berry, thanks so much for being with us this week on Connecting ALS.
Dr. James Berry:
Thanks for having me. I'm really excited to be here.
Jeremy Holden:
It's a great topic, I'm really looking forward to kind of unpacking some of this for listeners. Recently, in the last couple weeks, new research was published on what we know about the IV dosage of Edaravone, so let's just jump right in. What do we know today that maybe we didn't know three or six months ago?
Dr. James Berry:
The research that you're talking about is a retrospective analysis that comes from a large insurance claims database. This is a database that encompasses millions and millions of people who have commercial insurance or Medicare Advantage insurance, so it doesn't include people who have Medicare and Medicaid insurance, which we can come back to later. But from those millions of people, we get a lot of records about how they move through the medical system. And one of those things is diagnoses, like ALS, and another piece of information we get is about prescriptions. And so using that data, we thought we could look back and sort of see how people did when they received IV Edaravone or when they didn't receive IV Edaravone at the diagnosis of ALS.
Jeremy Holden:
And what did we learn?
Dr. James Berry:
So the first thing I'll acknowledge is that this is a complex analysis to do, and it took many, many, many months with a collaborative team working on this to really try to ferret out what's relevant here and what could be a red herring or leading us down the wrong path. And what we found is that when we did all of those corrections that people who were receiving IV Edaravone lived about six months longer in this data set than people who are not receiving IV Edaravone. And that's really I think one of the first times that we've seen a survival benefit to the drug. And to see it in this real world environment was really, I think,
Jeremy Holden:
It is interesting. I want to take a little bit of maybe a side track because I think about the process of science, and we think from idea, to testing, to clinical trials, and approval, this is kind of post approval. How common is this level of analysis to say, "We learned enough to get through the approval process, but we're going to want to go back and see what more can we learn through kind of real life experiences"?
Dr. James Berry:
I think it's becoming more and more common. Although, I'll acknowledge it's been going on for a long time. I mean, if we look at Riluzole for example, the approval of Riluzole was quite controversial at the time. Some people saying there wasn't enough evidence, or the effect wasn't big enough, or maybe it wasn't real. It was approved and then over the years we've seen many, many, different papers that have looked at Riluzole's effect in different ways and most of them have centered on some slowing effect on the disease. I think it's the fact that we have those original randomized control trials as well as follow-up data that says that there is a benefit that has led to a broader acceptance, I think, of the original trials. It's not uncommon. We're beginning to see a few of these analyses be done and [inaudible 00:04:39] there are a couple studies have been done post-marketing for Edaravone that didn't show a survival benefit and those are different study designs. I think it's a sum of all of the data that we have to look at to see what we think is, where the truth may be at.
Jeremy Holden:
I would imagine that will become more commonplace and maybe more necessary as more treatments do come online, and now we're looking at different cocktails and how they interact with different patients that have different risk factors.
Dr. James Berry:
Exactly, looking at subgroup analyses or looking at, actually more than subgroup analyses, what we may end up with is randomized trials that look at a very small slice of people with ALS that is a very restrictive inclusion criteria and then real world studies that look at a much broader staff of people with ALS who are taking these drugs. I think they're really valuable to supplement the data that we have from the randomized trials. Having said that, the data from the randomized trials is probably the highest quality data because it, in science what we'd like to do is test one question at a time, one variable at a time, and randomized trials are designed to do that. Real world evidence says, "okay, the word is messy. But let's try to gather all the information we can despite that mess". And we have methods that allow us to really get rid of variables that we think may sway our data one way or another but not in a real way.
Jeremy Holden:
You mention that the data set that was studied here was commercial insurance, private insurance, not traditional Medicare. Can we extrapolate from what we know and make maybe educated guesses or maybe inform future research so that we have a deeper understanding of the Medicare audience or whether this translates to a bigger slice of the population.
Dr. James Berry:
That's a good question. It's easy to get out ahead of our skis here because it's be easy to say, "Well, gosh, I really think what's the difference between somebody who's in a Medicare database and somebody who's in a commercial database?". And that's one way of looking at it. Another way of looking at it is, "Well, maybe there are substantial differences". So I want to be careful in how I answer that. Sometimes we just need the data to be able to kind of answer. The reason to go to a commercial database like this is that it's very comprehensive. So it has millions and millions of people and a lot of data about those people and it's not one commercial insurance, but broadly lots of insurances. And so if people switch carriers in the middle we can still follow their progression throughout the disease. It really provided the opportunity to look at this question in a lot of detail and follow people [inaudible 00:07:10] I think the right tool for this question. Being able to go beyond that, I think there are reasons to think that it would be reasonable to extrapolate this, but I also think that it's always best to begin to think about how we might get that data too.
Jeremy Holden:
The data set look at use of IV Edaravone. As listeners are well aware, an oral form was approved by the FDA for use in the treatment of ALS earlier this year. Are we able to do any type of educated guesses or extrapolation to think of what this might mean for the oral formulation?
Dr. James Berry:
This is a great question. The truth is that it goes all the way back to the randomized trials and how do we think about those as well. The data that came out about oral Edaravone is that the amount of Edaravone, the drug, that gets into the blood stream is really equivalent between the oral dosing and the IV dosing. So there weren't additional studies that said, "Let's compare placebo and oral Edaravone" because we've already said with IV Edaravone, a certain amount of drug gets into the blood and in those trials we saw that there was a benefit in slowing the disease in ALS [inaudible 00:08:21]. The studies comparing oral to IV said, "Look, the same amount of drug gets to the blood stream whether you take it by it's oral route or whether you take it the IV route". And so, I think a reasonable assumption, or hypothesis, or theory from there would be to say if you have the same amount of drug, whether it got there through the oral formulation or the IV formulation, it should have the same effect.
Jeremy Holden:
I want to switch gears a little bit, I think. Recently, with oral Edaravone, and now we're seeing similar discussions happen with [inaudible 00:08:52], or other potential treatments facing PDUFA dates. There's a lot of chatter in the community about access, approval turns out isn't the finish line. Access is the next conversation to happen. What have you seen in the marketplace that either inspires hope or frustration about some of those conversations around access?
Dr. James Berry:
I think we see hope and frustration together. The frustration probably goes way beyond just the ALS community, I'll say. This is something that we see, we read press stories about it in basically every disease that you can think of. From diabetes and insulin, to antibiotics and pediatric care. Access to drugs is a really big issue. And now when we talk about new drugs that are expensive and that are regulated by insurance ad insurance carriers in a really heavy way, I think there are a lot of hoops to go through. When a new drug comes out, nobody is on that drug. And so, there's a big push to get lots of people access to the drug all at once, and so we're trying to sort of really push a huge volume of referrals for that medication through a system that's really been built for a slow trickle, which is where we get eventually, hopefully, so that everybody who has the disease is on the right drug and then we don't have as many people at a time trying to get access. The other thing that's happening when a drug first becomes available is that, it's the first time that, many time's, insurance companies are seeing that drug and even in some cases that indication at all, that disease. And so, they don't have policies written about this and they need to go out and go to the community, really, and find out, how do we think about this drugs effect? Is this a drug that's supposed to stop or reverse the disease? Does that mean we stop covering it if it doesn't reverse the disease? Well, we know for the drugs in ALS that's not the case. But, not everybody is an ALS expert so we have to lend that expertise to be [inaudible 00:10:53].
Jeremy Holden:
That makes all the sense in the world. I want to stay on the subject of hope before I let you go back to the important work that you're doing. We're in that season of looking back on the year that was, and looking ahead to the year that will be. Do you see anything on the horizon or anything in the current landscape of ALS research that inspires hope that real progress is on the horizon?
Dr. James Berry:
What a year to look back on. We have the approval of oral Edaravone, we have the approval of [inaudible 00:11:24] in the US, and we have the submission and review of Tofersen for SOD1 ALS. I mean, to have all of that happen in a year is just remarkable. We're very much looking forward to next year and potentially new approvals next year, but we also see a really robust ALS trials landscape where every part of ALS trials is being rethought. We have the HEALY ALS Platform Trial that is sort of redefining how many drugs we can test at a time and how efficient we can be at testing that. That allows us just to look faster and to get the answers faster because we're able to look faster and more efficiently and allow more people to have access to these experiments and therapies along the way.
We're rethinking expanded access programs and how they fit into our landscape and bringing more expanded access programs to people with ALS, as well, and thinking about how did those expanded access programs exist as a part of drug development, and how do they help us generate data? And then there are just more trials going on now than ever before and those trials are based on more science, better models, than ever before. We're also seeing endpoints that are being iterated on so that ALS [inaudible 00:12:38] can be done by self entry, the roads is a new self entry scale. We have scales that can't [inaudible 00:12:44] our function and fatigue. And we're also finding new biomarkers like [inaudible 00:12:49] is coming, basically making its way into basically all trails, and digital biomarkers are also making an impact on the kind of data we can collect in trial. Every part of the machine is really moving forward. I think there's a lot of reason for how.
Jeremy Holden:
It echoes other things that I've heard from folks that have been fortunate enough to talk to you. A hopeful note to close on, Dr. Berry thanks so much for your time.
Dr. James Berry:
Absolutely. Thanks for having me.
Jeremy Holden:
I want to thank my guest this week, Dr. James Berry. If you liked this episode, share it with a friend. And while you're at it, please rate and review Connecting ALS wherever you listen to podcasts. It's a great way for us to connect with more listeners.
Our production partner for this series is CitizenRacecar, post-production by Alex Brauer, production by Gabriella Montiquine, supervised by David Hoffman.
That's going to do it for this week's episode, thanks for tuning in. We'll connect with you again soon.
ConnectingALS_121522_Ready1 (Completed 12/14/22)
Transcript by Rev.com
Page of