The director of the ALS Clinic at Massachusetts General Hospital pointed to the robust pipeline and meaningful gains in knowledge about the disease as reason to be hopeful.
Merit E. Cudkowicz, MD, MSc
As excitement builds for the future of treatment in amyotrophic lateral sclerosis (ALS), the physicians treating seem to finally feel as though there might be something big on the horizon.
Merit E. Cudkowicz, MD, MSc, is one of those physicians. The chief of the Neurology Service, director of the Amyotrophic Lateral Sclerosis Clinic, and co-director of the Neuromuscular Division at Massachusetts General Hospital pointed to the robust pipeline and meaningful gains in knowledge about the disease in recent years as her reasoning for hopefulness.
To gain more insight into the state of care for ALS, NeurologyLive spoke with Cudkowicz to find out her thoughts on the pipeline and the available therapies.
The pipeline is actually pretty huge, which is a good thing. There are 3 approved drugs out there right now, fully approved drugs for ALS, I know you know this right, riluzole, edaravone, and nuedexta. Nuedexta is more of a symptomatic treatment. I don’t know the exact number, but there might be more than 20 active clinical trials. There’s a lot of excitement about the gene therapy approaches for the genetic forms of the illness. This is a small subset of patients, but Biogen and Ionis Pharmaceuticals have launched an Antisense oligonucleotide for SOD1 ALS, and soon C9 ALS, and there are lots of other companies in that space—of how to turn off those genes. Given the success of spinraza for spinal muscular atrophy (SMA), there’s a lot of hope that for the genetic forms, we might be very, very close to something— if not a cure, some really super meaningful treatments. The field is also setting up for how to do pre-symptomatic trials, and in those populations—if those treatments end up being safe and effective—maybe people, won’t have symptoms. There are actually a lot of companies in that space for a very rare form of a rare disease.
They’re all good, and you can actually use them all in combinations. Riluzole was obviously the one out there first—it’s been around since the 90s. Reproducibly, every study that’s looked at it, it has about a 10% better survival and it’s very safe. It’s not a huge effect, but it’s a consistent one. The edaravone, which just came out last year was an add-on study. Everybody was on the riluzole and then the effect of edaravone was seen on top of that of about one-third of the progression of the illness. I do recommend, for my patients, that they take both. There’s no negative interaction, if anything, there was a positive interaction.
Then, nuedexta is FDA-approved for immobility that have some of the patients have. There’s also been a trial that showed that it also helps people’s speech and swallowing function. So, it’s actually for all 3 of those symptoms, and can be given with the riluzole and edaravone. Many of my patients are on all three.
We’ve learned a lot. A couple companies have told me when they look at the ALS landscape, it’s so prime for success. It’s got the ingredients in there now—we have tools to measure the illness, we have consortia, globally, that are working on trials together and centers where people can go to work on trials, there’s a lot of knowledge on how to take care of patients, and there’s always new targets.
One of the targets that people are excited about, including myself, include the role of this protein TTP43 in ALS. It seems to be involved in almost all forms of ALS. It’s very important for how hardening metabolism happens, and there are several companies that are trying to tackle fixing the problems of TTP43. There’s nothing in trials with that now, but they’re coming up, and there’s a lot of excitement about that. There’s also a new appreciation of the role of immune system in the illness—probably in it having a role in how the illness spreads and the pace of the illness. There are probably 10, if not more, drugs that are in either in trials or about to go into trials looking at ways to dampen that neuroinflammation.
Then, the edavarone story kind of brought back the idea of oxidative toxicity as a role. There’s a company called Treeway that’s actually made an oral version of that drug that’s going to go into trials, hopefully soon. Taking some of that success and trying to make it even more successful and easier for patients.
A big change in the field has been that there are so many more people involved in it. We used to get everyone around the table, maybe 25 to 50 people in the 90s, and now it’s really thousands, globally. The last time I counted, there are more than 80 companies with ALS programs. So, it really does feel like a changing point where, we’re going to be like multiple sclerosis, where we won’t have 2 or 3 drugs to pick from, but 15 drugs to pick from in the next couple years.
Our biggest challenge is really understanding, is this one disease or a hundred diseases? Most of the field feels like there are lots of ways you get to getting ALS, and the treatments might really need to be more individualized in developing those tools to try and figure it out. I use the cancer comparison often. In breast cancer, we know there’s about 50 different types of breast cancer, and now they take a test and tell you your gene status and they tell you what the best treatment approach is for you. We need to get there for ALS.
There are projects—there’s one large one called Answer ALS, which is actually trying to sort that out, using genomics and other gene technology and imaging, to try and really see if we can subset people out so that we can target the drugs better. That’s our biggest challenge for trials. When you take maybe a couple hundred people and they’re all in the same trial, but maybe only a third of them are going to respond to drugs because they have the target that that drug is going after.
I would say to the general neurologist that it’s an exciting time to be in the ALS field, there’s a lot more people entering it, and we need even more people to take care of patients with ALS.
Transcript edited for clarity.