The Dravet syndrome community has long been awaiting gene therapy approaches to provide true disease-modifying treatments. We now watch optimistically as new therapies are in final stages of pre-clinical development or are beginning early-phase clinical trials. One of the challenges of these types of gene-based therapies entering human clinical trials is that a placebo-control approach becomes increasingly more complicated, but without a control group it is difficult to assess the effectiveness of an experimental therapy. An approach to reduce the need for placebo groups is to form a clearly defined picture of the disease progression through a Natural History study, which can then be compared to outcomes following treatment. Natural History studies are observational assessments of patients over time and collect medical information to understand how symptoms progress and are treated. For Dravet syndrome, this includes understanding the range of progression of seizure activity as well as cognitive, motor, and behavioral development. Natural History studies are only to observe the natural course of disease and do not provide any type of experimental intervention outside of the normal care and treatments that are managed by the patient’s physicians. Even if a placebo group is still required for a future clinical trial, the results of a Natural History study can help researchers to tailor the outcomes they measure based on meaningful data that is truly representative of the challenges patients and their families face.
Encoded Therapeutics has a new genetics-based approach to treating Dravet syndrome using a viral vector that acts as a package to deliver genetic material to the primary neurons affected by the SCN1A mutation. This new therapy, called ETX101, does not provide a new copy of SCN1A, but rather delivers a gene that can increase expression of the healthy copy of SCN1A. This is particularly exciting because traditional gene therapy approaches are limited for SCN1A because the gene is too large for the currently available viral vector packaging. ETX101 circumvents that limitation by targeting the gene-level regulation of SCN1A. Encoded Therapeutics obtained Orphan Drug Designation and Rare Pediatric Disease Designation by the FDA for ETX101 and plan to enter Phase I clinical trials in 2021. With a treatment approach on the horizon, Encoded Therapeutics is also recognizing the need to have a full assessment of Dravet syndrome progression that extends beyond seizure frequency. To that end, they are now actively enrolling for a Natural History study called ENVISION.
The ENVISION Study is an observational study of children aged 6 to 60 months with SCN1A-positive Dravet syndrome. ENVISION is designed to better understand the seizure, neurodevelopmental, motor and behavioral characteristics of Dravet syndrome over a period of 2 years using standardized assessments. The ENVISION study will also explore the impact of Dravet Syndrome on parents/caregivers over the same period. This study will be conducted at study centers in the United States, Australia and the United Kingdom and visits to the clinic for this study will occur every 6 months over the 2-year participation period. ENVISION is a non-interventional study, which means that no treatments or investigational medications will be provided. Patients will receive their usual medical care and will be monitored in the study at regular intervals. The information collected in ENVISION may advance the understanding of Dravet Syndrome and potentially support development of novel therapies.
More information about the ENVISION study, including a list of participating centers, can be found at ClinicalTrials.gov. If you locate a participating site that you are interested in, you or your physician may contact that site directly for more information.
This summer, Encoded Therapeutics participated in a webinar series where they talked more about the plans for the ENVISION study, as well as some information on their experimental therapy, ETX101. You can find the webinar on this page.