IEC 2023 | Comparing the efficacy and safety of add-on therapies in Dravet syndrome
Delphine Vandame, PhD, Biocodex, Orphan Disease Division (HQ), Gentilly, France, discusses her recent study comparing the efficacy of different first-line add-on therapies in Dravet syndrome (DS). Currently, there are three add-on therapies licensed for this indication. Stiripentol was initially licensed for treatment in 2007, then more recently cannabidiol and fenfluramine have become licensed. However, there have been no clinical trials comparing the efficacy and safety of these therapies. Therefore, Dr Vandame and her group aimed to compare the efficacy and safety of these three therapies, by undertaking a literature review and network meta-analysis of randomized control clinical trials (RCT) investigating each therapy. The group discovered a higher proportion of patients achieved reductions from baseline in monthly convulsive seizure frequency (MCSF) of ≥50% and ≥75% when treated with stiripentol and fenfluramine, compared with cannabidiol. However, a higher proportion of patients achieved reduction from baseline MCSF of 100% (seizure free) with stiripentol in comparison to both cannabidiol and fenfluramine. There were no differences observed in safety outcomes between all three therapies. This interview took place at the International Epilepsy Congress 2023 in Dublin, Ireland.
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Transcript (edited for clarity)
We were presenting new data during this International Epilepsy Congress about indirect comparison of treatment for use in Dravet syndrome. Dravet syndrome is a really devastating disease, most patients are inadequately controlled with standard of care, so they request additional add-on therapy. And right now, on the market, you have a stiripentol, fenfluramine, and cannabidiol. Stiripentol was then first-in-class, best-in-class drug, and fenfluramine and cannabidiol were developed later on...
We were presenting new data during this International Epilepsy Congress about indirect comparison of treatment for use in Dravet syndrome. Dravet syndrome is a really devastating disease, most patients are inadequately controlled with standard of care, so they request additional add-on therapy. And right now, on the market, you have a stiripentol, fenfluramine, and cannabidiol. Stiripentol was then first-in-class, best-in-class drug, and fenfluramine and cannabidiol were developed later on. But for the clinical trials, it still didn’t include the stiripentol as an active treatment. So, what we decided to do is really to compare efficacy and safety for these three drugs.
We decided to use robust methodology, a network meta-analysis. For that we decided to have a strong literature review to see which data we would like to select and the most appropriate data were two placebo-controlled, randomized clinical trial for each single drug. In total, six trials and we decided to compare for efficacy on the outcome of the monthly convulsive seizure frequency, and what we would like to compare is the percentage responder rate.
So first we compare for patients who had at least reduce 50% of their seizure frequency, and what we could see there isn’t any difference between stiripentol and fenfluramine, but it’s higher compared to cannabidiol for the outcome. And decreasing at least 75% of seizures we could see almost the same result: stiripentol and fenfluramine had no difference, but better than cannabidiol. And for the last outcome, 100%, that means seizure free for patients, so the really strong and profound response, we could see a difference. Stiripentol is doing better and statistically significant compared to fenfluramine and cannabidiol.
What we would like to do as well is to compare the safety profile to be sure that there isn’t any difference. We considered serious adverse events and discontinuation for serious adverse events, and we didn’t see any difference between the three drugs. So, with this work we could conclude that stiripentol as a first line add-on therapy in Dravet syndrome is at least as effective as fenfluramine and more than cannabidiol in reducing convulsive seizure with no greater risk of seizure adverse events. We could consider a stiripentol as a backbone treatment for Dravet syndrome. We are publishing this data soon.
Right now, we have guidelines to treat Dravet syndrome, first line is valproate. And as I mentioned, stiripentol, fenfluramine, and cannabidiol are add-on therapy. To better know which profile and which patient could benefit from which drug, it could be a better help for physicians. And as well, we could consider the cost effectiveness of this drug, and with that we could have a better value proposition for stiripentol.
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Disclosures
Delphine Vandame is an employee of Biocodex.
