CAMBRIDGE, Mass. and BEDFORD, Mass. — Biogen Inc. (Nasdaq: BIIB) and Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine, today announced the presentation of longer-term follow-up analyses from the ongoing open-label extension (OLE) studies of zorevunersen that support the potential of zorevunersen as a disease-modifying medicine for Dravet syndrome. These new results were presented at the 54th Child Neurology Society (CNS) Annual Meeting.
New two-year data from an analysis that was initially performed to understand the potential effects of the Phase 3 dosing regimen on cognition and behavior showed continuing improvements at two years. These results contrast with findings from a two-year natural history study in which patients with Dravet syndrome who were treated with standard of care showed minimal changes in cognition and behavior. In addition, the companies presented three-year results from analyses of Clinical and Caregiver Global Impression of Change (CGI-C and CaGI-C) scales measuring overall clinical status, which complement previously presented EQ-VAS caregiver-reported quality of life improvements. Caregivers and clinicians separately reported similar improvements in overall clinical status in 95% of patients treated with zorevunersen (n=19).
“Data from the ongoing open-label extension studies are helping to shape our understanding of the long-term effects of zorevunersen on seizures, cognition, behavior and overall functioning, which together support the potential for disease modification,” said Kelly Knupp, MD, MSCS, Professor of Pediatrics and Neurology at the University of Colorado Anschutz and the Dravet Program Director and Epilepsy Program Lead at Children’s Hospital Colorado. “The natural history data continue to provide important context for the effects we are seeing in patients treated with zorevunersen. Improvements in cognition and behavior are not something we see in patients with Dravet syndrome, and rarely do we see such strong correlation between caregiver and clinician-reported outcomes. Together, these data are starting to paint a fuller picture of the potential impact disease modification could have on a patient’s overall health and daily living.”
These data were among several analyses included in a poster presentation of data from the Phase 1/2a and ongoing OLE studies of zorevunersen. Safety and tolerability were the primary endpoints of these studies. In addition, effects on major motor seizure frequency, cognition and behavior were assessed as secondary endpoints. As previously reported, results showed substantial and durable reductions in major motor seizure frequency and improvements in multiple measures of cognition and behavior on top of a background of standard anti-seizure medicines through three years. The most substantial reductions were observed among patients who were treated with loading doses of 70mg in the Phase 1/2a study followed by maintenance doses of 45mg. This regimen is now being evaluated in the Phase 3 EMPEROR study.
Summary of Safety Data
Eighty-one patients received at least one dose of zorevunersen and have been evaluated for safety. Zorevunersen has been generally well tolerated across the Phase 1/2a and OLE studies. Study drug related treatment emergent adverse events (TEAEs) were observed in 30% (24/81) and 53% (40/75) of patients treated in the Phase 1/2a and OLE studies, respectively. The most common study drug related TEAE was CSF protein elevations reported in 14% (11/81) of patients in the Phase 1/2a studies and 44% (33/75) of patients in the OLE studies. CSF protein elevations (>50 mg/dL) occurred in 42% (34/81) of patients in the Phase 1/2a studies and 86% (62/72) of patients in the OLE studies. No related clinical manifestations have been observed although one patient discontinued treatment due to elevated CSF protein levels. Treatment-emergent serious adverse events (TESAEs) were reported in 22% (18/81) and 29% (22/75) of patients in the Phase 1/2a and OLE studies, respectively, all of which were assessed to be unrelated to study drug except one patient who experienced SUSARs.
Details of the Presentation
Title: Zorevunersen demonstrates disease-modifying potential in patients with Dravet syndrome through durable seizure reduction and continuing improvements in cognition, behavior, and functioning through 36 months of treatment in open-label extension studies
Presenter: Joseph Sullivan, M.D., FAES, Professor of Neurology and Pediatrics and Director of the Pediatric Epilepsy Center of Excellence at the University of California San Francisco
Session: Poster Review & Guided Abstract Tours
Date and Time: Thursday, October 9, 12:30-1:45 PM and 5:30-7:00 PM ET
Poster Number and Location: Poster #92, Hall C, Charlotte Convention Center, Charlotte, NC
The presentation will be available for download on the Stoke Therapeutics website under the Investors & News tab.
About Dravet Syndrome
Dravet syndrome is a severe developmental and epileptic encephalopathy (DEE) characterized by severe, recurrent seizures as well as significant cognitive and behavioral impairments. Most cases of Dravet are caused by mutations in one copy of the SCN1A gene, leading to insufficient levels of NaV1.1 protein in neuronal cells in the brain. More than 90 percent of patients continue to experience seizures despite treatment with the best available anti-seizure medicines. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. Developmental and cognitive impairments often include intellectual disability, developmental delays, movement and balance issues, language and speech disturbances, growth defects, sleep abnormalities, disruptions of the autonomic nervous system and mood disorders. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP. Dravet syndrome occurs globally and is not concentrated in a particular geographic area or ethnic group. Currently, it is estimated that up to 38,000 people are living with Dravet syndrome in the U.S. (~16,000), UK, EU-4 and Japan.1 There are no approved disease-modifying therapies for people living with Dravet syndrome.
About Zorevunersen
Zorevunersen is an investigational antisense oligonucleotide that is designed to treat the underlying cause of Dravet syndrome by increasing functional NaV1.1 protein production in brain cells from the non-mutated (wild-type) copy of the SCN1A gene. This highly differentiated mechanism of action aims to reduce seizure frequency beyond what has been achieved with anti-seizure medicines and to improve neurodevelopment, cognition, and behavior. Zorevunersen has demonstrated the potential for disease modification and has been granted orphan drug designation by the FDA and the EMA. The FDA has also granted zorevunersen rare pediatric disease designation and Breakthrough Therapy Designation for the treatment of Dravet syndrome with a confirmed mutation not associated with gain-of-function, in the SCN1A gene. Stoke has a strategic collaboration with Biogen to develop and commercialize zorevunersen for Dravet syndrome. Under the collaboration, Stoke retains exclusive rights for zorevunersen in the United States, Canada, and Mexico; Biogen receives exclusive rest of world commercialization rights.
About Biogen
Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patients’ lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth.
We routinely post information that may be important to investors on our website at www.biogen.com. Follow us on social media – Facebook, LinkedIn, X, YouTube.
About Stoke Therapeutics
Stoke Therapeutics (Nasdaq: STOK), is a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine. Using Stoke’s proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) approach, Stoke is developing antisense oligonucleotides (ASOs) to selectively restore naturally-occurring protein levels. Stoke’s first medicine in development, zorevunersen, has demonstrated the potential for disease modification in patients with Dravet syndrome and is currently being evaluated in a Phase 3 study. Stoke’s initial focus are diseases of the central nervous system and the eye that are caused by a loss of ~50% of normal protein levels (haploinsufficiency). Proof of concept has been demonstrated in other organs, tissues, and systems, supporting broad potential for Stoke’s proprietary approach. Stoke is headquartered in Bedford, Massachusetts. For more information, visit https://www.stoketherapeutics.com/.
Reference
- Based on Stoke Therapeutics’ preliminary estimates, which scaled annual incidence to prevalence using country-specific live birth rates over the past 85 years and adjusted for Dravet-specific mortality. The estimate is based on incidence rates published by Wu et al., Pediatrics, 2015.
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