The 2024 DSF Family & Professional Conference took place June 20th to 22nd at the JW Marriott Minneapolis Mall of America in Minnesota. The meeting brought together the community of patient-families, clinicians, researchers, and industry professionals to connect, learn from one-another, reflect on progress, and discuss the outstanding needs for individuals living with Dravet syndrome (DS). These three days were full of engaging educational sessions combined with opportunities for meaningful connections and conversations. In today’s blogpost I will provide an overview of the topics discussed in the educational sessions and some of the highlights I took away from the conference.
If you were unable to attend the conference, but would like to view the recorded sessions, you can purchase an access pass for $75 by clicking on this link. If this cost poses a financial burden for you, please contact us at conference@dravetfoundation.org. Starting in January 2025, all recordings will be freely accessible on our website.
The Current Treatment of DS
Dr. Linda Laux helped to kick off the conference by providing a historical overview of DS. She reflected on progress since the first recognition of DS as a unique clinical diagnosis in the late 1970s (then called severe myoclonic epilepsy of infancy, or SMEI) to the current day where we not only understand the most common genetic cause (mutations in SCN1A) but are also seeing new treatments that aim to treat that cause. This overview set the stage nicely for Dr. Elaine Wirrell to open the professional sessions on Friday focused more acutely on the clinical presentation and treatment of DS. Dr. Wirrell referenced the most recent expert clinical consensus on top-line treatments for DS. Some of these top-line anti-seizure medications in the treatment consensus, Fintepla (fenfluramine), Diacomit (stiripentol), and Epidiolex (cannabidiol) have all received FDA-approval specifically for DS since 2018. During our Thursday sessions, we were able to hear presentations from the manufacturers of these three medications (UCB, Biocodex, and Jazz, respectively) on the evidence for effectiveness from clinical studies as well as additional research that has indicated there may be other positive impacts on patient quality of life measures related to these medications. Other top-line treatments that did not have individual presentations included Depakote (valproate) and Onfi (clobazam).
Dr. Douglas Smith followed up and discussed the management of prolonged seizures, including the importance of seizure action plans, at-home seizure rescue medications, and current recommendations on hospital treatment for status epilepticus. There were also industry presentations that focused on two newer at-home rescue medications Valtoco (diazepam nasal spray) from Neurelis and Nayzilam (midazolam nasal spray) from UCB.
Another topic that comes up often in the community regarding treatment options is neurostimulation. Dr. Keith Starnes discussed how vagus nerve stimulation (VNS) is already used regularly in DS, with modest results on seizure reduction; although studies have shown caregivers do often note additional benefits with VNS beyond a reduction in the number of seizures. Â Dr. Starnes also discussed the limited evidence for deep brain stimulation (DBS; only 2 studies in DS) as well as some non-invasive brain stimulation techniques like transcranial magnetic stimulation (TMS) that are still being investigated in DS and other similar epilepsies. In summary, neuromodulation remains generally under-studied in DS and while it is unlikely to lead to complete seizure freedom, there is growing evidence to support its benefit and the field is rapidly developing new approaches that may also be applicable to DS.
Lastly, when discussing seizure control and DS, it is important to acknowledge the risks that patients with DS face surrounding prolonged seizures, seizure-related accidents, and sudden unexpected death in epilepsy (SUDEP). While the majority of children diagnosed with DS do grow-up to become adults, there is a known risk of 10-20% for premature mortality. Dr. Linda Laux and Tom Stanton from the DannyDid Foundation presented on some of these risks as well as methods to mitigate risk including working to achieve the best seizure control possible and becoming educated about seizure monitoring devices. Caregivers Jen Kuhn and Rich Maxey also participated in a panel with Dr. Laux and Tom discussing experiences with seizure monitoring devices and night-time monitoring. Danny Did Foundation has more information on seizure detection and safety devices as well as grants that support families in purchasing those devices. In addition, DSF offers patient assistance grants that can also be used to support the purchase of a seizure safety or detection device.
New Treatments in Development
Dr. Scott Perry gave an overview of current clinical trials for DS in his session on Friday, touching on some of the basic concepts and considerations around clinical trial design and participation as well as the results and progress of recent clinical studies. We also heard directly from some of the companies sponsoring clinical studies for new therapies.
- Longboard Pharmaceuticals discussed promising results of sustained seizure reductions from their Phase 2 and open-label extension studies of bexicaserin (LP352) that included three patients with DS in addition to participants with other developmental and epileptic encephalopathies (DEEs). Bexicaserin targets the serotonin pathway (5HT2C receptor superagonist). They hope to begin Phase 3 studies by the end of 2024.
- Takeda discussed the recent results from the Phase 3 study of soticlestat. While the study just narrowly missed the end point of a significant reduction of seizures in patients with DS, the company expressed they will be preparing for discussions with the FDA as they might have evidence to support improvements in secondary outcome measures.
- Harmony Biosciences discussed the actively enrolling ARGUS study for EPX-100 (clemizole HCl). Clemizole was discovered as a potential effective therapy in a zebrafish model of DS, thought to be effective through action on the serotonin pathway (agonist to 5HT2B, 5HT2C, and 5HT2A receptors).
Dr. Laux mentioned in her talk that there are several anti-seizure medications approved for other types of epilepsy that we are just beginning to understand whether they may be effective for patients with DS (i.e. Fycompa [zonisamide], Briviact [brivaracetam], Xcopri [cenobamate]).
Certainly, one of the very exciting prospects on the horizon for the treatment of DS is targeting the disorder at the genetic cause. Dr. Perry gave an excellent explanation of the two genetic therapies that are in clinical studies right now, STK-001 (now with the generic name zorevunersen) from Stoke Therapeutics and ETX101 from Encoded Therapeutics.
- Stoke Therapeutics also presented directly at the conference, updating the community on the Phase 1/2 and open-label studies for zorevunersen/STK-001 reporting significant reductions in seizure frequency as well the first indications of positive impacts on developmental domains. Stoke Therapeutics is currently working on a global program for a Phase 3 study, which they anticipate will likely start in 2025.
- Encoded Therapeutics is actively enrolling the ENDEAVOR trial for ETX101 in the US for patients with DS between the age of 6 to 36 months.
You can find these recent blog posts that provide additional details on zorevunersen/STK-001 and ETX101.
Dr. Joseph Sullivan and I also presented with a slightly more zoomed out view on the prospects for genetic-based therapies for DS in the morning session on Saturday. Another talk of relevance to this topic was delivered by Dr. Ingo Helbig covering the current knowledge of the genetic cause of DS and other SCN1A-related disorders and the return of his popular “know your g./ c./ p.“ discussion about understanding the information on your loved one’s genetic report.
Find listings for actively enrolling clinical studies and the pipeline of therapies in development for DS at dravetclinicaltrials.org
Comorbidities and Care Over the Lifetime
Several presentations at the conference focused on navigating adulthood with DS. Dr. David Burkholder focused his talk on the overall adult presentation and considerations for medical care in adults with DS. Dr. Danielle Andrade then gave an overview of some of the gait and motor issues that may worsen during adulthood and some of the ongoing research to better understand these symptoms and potential treatment approaches. On Saturday, there was an afternoon workshop that focused on a new Caring for Adults with Rare Epilepsy (C.A.R.E.) Binder developed in collaboration with UCB, DSF, the LGS Foundation, and TS Alliance. The C.A.R.E. Binder is an adaptable, fillable workbook that lays out the many topics and considerations for long-term planning around an adult with a rare epilepsy like DS. A website dedicated to the C.A.R.E binder and related resources for families is coming soon! The session not only covered the content contained in the binder, but also included several family-led panel discussions covering tips and experiences navigating the transitions that occur as their loved ones reach adulthood.
Beyond the burden of seizures, behavior, cognition, and sleep are concerns that often rise to the top when speaking with families. At the conference, Dr. Priscilla Duong spoke about neuropsychiatric care for patients with DS, outlining the current approaches to assessment and treatment, while acknowledging that research in this area is still lacking to inform guidelines. Dr. Chris Matarese then spoke on sleep disruptions in DS, noting the importance of sleep routines and again referencing the limited repertoire of therapies that have limited evidence to inform how effective they are across the population; melatonin seems to have the most support as effect for patients with DS. Again, Dr. Matarese concluded by noting how further research could be beneficial for establishing guidelines and assessing efficacy of interventions.
Family-focused Sessions
Some additional sessions focused more closely on advocacy and day-to-day challenges for families including a presentation from licensed clinical social worker Paula Roberts on ways to access resources local to you to support your loved one’s needs; how to engage in legislative advocacy and some of the new efforts DSF has engaged in to advocate on behalf of the community; engaging in education about DS and fundraising for research through DSF; and a session led by DSF family advocacy-staff on balancing hope and reality as families face the diagnosis and journey with DS.
Important Research Studies
The research team from Children’s Hospital of Philadelphia attended the conference to recruit participants for their $1M clinico-genomic project funded by DSF that aims to collect saliva samples from 500 patients with SCN1A-related epilepsy for whole genome sequencing. That genomic data will then be paired with clinical information from the electronic health record to help contribute to our understanding of the variable clinical outcomes for patients with DS (such as cognitive and motor outcomes, medication responses, seizure burden, etc). You can read more about the study and how to participate in this blog post or by emailing scn1a@chop.edu for more information.
Dr. Christos Papadelis presented on his research efforts at Cook Children’s in Fort Worth to find non-invasive biomarkers for DS, with promising preliminary results looking at electrophysiological markers of GABAergic signaling, which has long been thought to be significantly impacted in DS. The idea is that with a non-invasive biomarker you may be able to determine if a therapy is effective in a way that introduces less external bias and may give indications of efficacy more quickly than it may take to observe secondary improvements for the patient in a clinical setting. This could greatly reduce the amount of time a clinical trial takes to show data that supports efficacy and could also potentially be of use in the trial-and-error process of selecting anti-seizure medications for patients. If you are interested in learning more about participation in these efforts and are the caregiver to a patient under the age of 18 years, email neuroresearch@cookchildrens.org.
Dr. Danielle Andrade’s research group is also looking at genetics and cardiac function in DS. They have been working to collect saliva samples for genetic sequencing as well as data from non-invasive heart monitors. If you are interested in participation, email quratulain.zulfiqar_ali@uhn.ca
I left this year’s conference exhausted from the busy days but with an energized spirit ready to continue the momentum that has advanced things to this exciting point for the DS community. The Wings of Hope Butterfly Release on Saturday morning was a reminder of those whose memory we are working in and the many patients still waiting on therapies and supports that can help them achieve their best quality of life. Research is robust and clinical care is being delivered better than ever before for patients with DS. However, there are still many unmet needs that underline the need to keep working diligently, but we are beginning to witness the next generation of therapies that have the potential to truly modify the course of the disease. At the conference we reflected on how many of the questions might have different answers in the future with the advancement of technology and knowledge, and I look forward to seeing how things have progressed when we come together again in two years for the next conference. Â
