Joseph E. Sullivan, MD: At the time that that trial was wrapping up, you and I participated in another trial of fenfluramine which has such a cool story in the sense that the whole story got started with just a small group of patients that were tried on fenfluramine not knowing that they had dravet syndrome and it was after the fact that, “Oh look, a lot of these patients have that history that we’ve talked about.” Some have dravet, and they ended up having variants in SCN1A gene and that led to this phase 3 clinical trial that had a pretty much identical inclusion criteria as the cannabidiol trial, just slightly different baseline but seizures were counted in the same. And I’m wondering, we both had a lot of patients in that trial, but what were your takeaway messages from fenfluramine?
Kelly Knupp, MD: The results were pretty impressive, right? There was a 75% reduction in seizures, in convulsive motor seizures in patients who were on the high dose of fenfluramine. And the low dose also saw more than a 40% reduction in seizures. Pretty impressive results from that. Again, it’s not the magic bullet for everybody, there are some patients where it didn’t seem to make a difference. There were some patients who did have some side effects that in the end they felt were intolerable. But there were also this group of patients that were seizure-free, or nearly seizure-free, and that was exciting. I prepare most of my patients that while we hope for seizure freedom, it’s not a realistic goal and we need to be cautious as we move forward to get to that goal. And here we have this new medication that came out and I think it was close to 25% of patients that were seizure-free or nearly seizure-free, which is fantastic. While we hoped for that, I don’t think any of us expected to see that.
Joseph E. Sullivan, MD: No, exactly. And I remember hearing the initial data from the initial Belgian group presented on a poster in Rome back in 2011, or 2012, and I was like, “Oh, that’s great, but how can I get it?” Almost frustrating, right? And people would ask me, “Do you really believe it?” And I was like, “Well, even if it’s half as good, that’s still going to be life-changing for a lot of patients.” And in my experience, patients are in a trial, patients I’ve started on it after the trial, it has been life-changing for some. The hard part for me is, you go into it obviously wanting the best for your patient, and as you mentioned, it doesn’t work for everyone, we do have to go into it with that tempered optimism. But we don’t know until we try, and that hopefully, that’s a direction that our field will move into as we have more genetic testing. And I’m just speaking off the cuff here, maybe there will be some different mutations or different types of patients that maybe respond better than others and the more that we get more details, the more that we’ll be able to maybe analyze that after the fact.
Kelly Knupp, MD: Wouldn’t it be fantastic if we could predict who was going to respond to what?
Joseph E. Sullivan, MD: Exactly, I know I remember one of my mentors telling me, “Why can’t we be like the infectious disease, where you swab the throat, it comes back with this, it’s sensitive to penicillin, you can look a family and say if you take this for 10 days you will get better.” That’s what need in epilepsy. And maybe, getting back to my comments about syndrome specific, these drugs are being studied in these syndromes and when we start to look at these different syndromes, they don’t share a whole lot of common denominators in terms of the cause, if they are working in multiple syndromes, maybe it’s not so syndrome specific. And Mary Anne, I’m curious as a new medication, you said that these medicines didn’t work for your son, is that what you said? Did you go into it with tempered optimism, or you’d kind of been there, done that, so you had low expectations or how did you handle that?
Mary Anne Meskis: I still went in with tempered optimism, we’ve seen so many positive changes in the field in the last 15-20 years and in addition to these we know right now of 7 other companies that either have a product in clinical trial, or should be in clinical trial by the end of 2022. And I just feel like we need to keep pushing that forward and trying out these options to see if they can afford a better quality of life for our patients. It is difficult and frustrating that the information on fenfluramine was compelling and of course, I hoped that he’d be one of the patients that responded, and he didn’t, but it’s still exciting for me to see and hear about patients that are going over a year seizure-free, that was just unheard of 5 years ago.
Joseph E. Sullivan, MD: Exactly. And you know, your son’s older when he tried and, understanding the evolution of the syndrome, I don’t know Kelly, at least in my practice today, I don’t necessarily feel like I have a silo of drugs for this stage, this stage and while I may be able to share some patterns or anecdotes, it’s taking it in the order, you have that mutual decision-making with the patient and the family, you present the data, you present the risk, you present the benefits, and it’s ultimately, unfortunately, they very likely are going to be tried on all of them, it’s just a matter of which order. Is that how you kind of approach things?
Kelly Knupp, MD: That’s how I approach things. Maybe at 3 you have a poor appetite, maybe fenfluramine doesn’t make sense and depakote does. Maybe at 8 you’re gaining too much weight, and so fenfluramine and the adverse effect profile of fenfluramine makes more sense. I do try to prepare families that at some point in time in their lifespan, your child will probably be on one of these medications. The last thing I – what I don’t want families to say is, “Oh, I’m never going to try that medication,” because we won’t know until we’ve tried it whether it’s going to work or not. Sometimes when families come in with this idea that, “I never want to be on medication X,” and we’ve tried everything else and I’m like, “Now you have to do medication X.” And then it’s the best medication, and they’re like, “Oh, I can’t believe I didn’t do this sooner.” It’s important for families to maintain that open mind that at some point in time you may have to do these.
Joseph E. Sullivan, MD: That is one of the big advantages of having our patient advocacy groups. Families, most of the time it’s a good thing, right? They can talk. I’m just kidding, but it’s great that they’re talking right? But you don’t want people to be sharing their bad experiences, well you do, but you don’t want them to be shared in such a way that it becomes a barrier to them trying it. Because there certainly are those stories where like, “Why didn’t I do this earlier?” That kind of stuff. And we should mention, it’s comforting that, Kelly, we haven’t even mentioned anything about the cardiac adverse effects, we talk about appetite and things. But I think there was also a lot of trepidation when the program started, but thankfully now, if we go back to the original Belgian cohort of 30 years, but even just the contemporary studies that now have been going on 5, 6, years still have not been any negative cardiac adverse effects which is really comforting and should hopefully – It took some brave souls to sign up for the trials early on because we didn’t necessarily know, but now, we do have a lot of comfort built into there about the adverse event profile.
Transcript Edited for Clarity