FDA Gives ET-101, Gene Therapy for ALS, Orphan Drug Status
Also called SynCav1, therapy aims to treat sporadic and familial disease forms
ET-101, Eikonoklastes Therapeutics’ experimental gene therapy for amyotrophic lateral sclerosis (ALS), has been designated an orphan drug by the U.S. Food and Drug Administration (FDA).
Orphan drug status is given to investigational therapies with the potential to significantly benefit people with life-threatening or chronically debilitating diseases that affect fewer than 200,000 individuals in the U.S.
The designation aims to speed ET-101’s clinical development and review, by providing regulatory support and financial benefits, as well as seven years of marketing exclusivity if the therapy is ultimately approved by the FDA.
Orphan drug designation “is critical for incentivizing the development of new treatments for rare diseases, especially those like ALS with severe morbidity and mortality,” Samuel Lee, Eikonoklastes’ president and chief business officer, said in a company press release.
By overproducing Caveolin-1 protein, ALS gene therapy could aid motor abilities
“Achieving [it] is an important regulatory milestone that further validates our efforts to efficiently develop ET-101. We look forward to rapidly advancing this novel technology towards our first-in-human clinical trial,” Lee added.
ALS is a progressive neurological disorder that affects motor neurons — the nerve cells that control voluntary movements — causing them to die. Over time, the brain loses the ability to control muscle movement, and muscles start to deteriorate.
Its exact cause remains unknown, but genetics are known to play a role. While about 90% of all cases are considered sporadic ALS and believed to arise due to a combination of environment and genetic factors, roughly 10% of patients have familial ALS, caused by specific genetic mutations. Eikonoklastes’ gene therapy aims to treat both forms of the disease.
ET-101, also known as SynCav1, is designed to deliver a copy of the Caveolin-1 gene to nerve cells using a harmless viral vector. This gene provides the instructions for producing a protein with the same name that helps organize and regulate receptors involved in nerve cell communication.
By increasing production of the Caveolin-1 protein, ET-101 is thought to be neuroprotective, helping nerve cells compensate for the nerve cell loss and improving motor function.
In a mouse model of ALS carrying a mutation in the SOD1 gene, ET-101 delivered to the spinal canal before disease onset was reported to delay the first signs of disease by about 15%. Notably, between 12% and 20% of familial ALS cases and 1% to 2% of sporadic cases are caused by mutations in this gene.
The treatment also extended average survival times by about 10%, and improved the mice’s performance on tests of motor function. Similar improvements in grip strength were observed in a rat model of SOD1-ALS.
“The FDA’s orphan drug designation for ET-101 reflects the compelling data underlying the ET-101 program and its potential as a 1st-in-class treatment option for both familial and sporadic ALS,” said Bruce Halpryn, chairman and CEO of Eikonoklastes.
“Our goal is to significantly increase survival and improve quality of life for patients with this terrible disease,” he added.
While Eikonoklastes is primarily focused on advancing ET-101 for ALS, the company believes it could also be an option for other neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Huntington’s, multiple sclerosis, and traumatic brain injury.
So far, the gene therapy also has shown promise in preclinical work in Alzheimer’s disease, where it delayed neurodegeneration and improved memory in a mouse model.
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