ALS Gene Therapy Momentum Continues With New Orphan Drug Designation


The FDA action follows a slew of recent cell and gene therapy updates in the field of amyotrophic lateral sclerosis.

The FDA has granted orphan drug designation (ODD) to ET-101 (Eikonoklastes Therapeutics), an investigational gene therapy for the potential treatment of amyotrophic lateral sclerosis (ALS).1

“The FDA’s ODD 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,” Bruce Halpryn, chairman and chief executive officer, Eikonoklastes Therapeutics, said in a statement.1 “Our goal is to significantly increase survival and improve quality of life for patients with this terrible disease.”

ET-101 is a first-in-class, AAV9-based gene therapy for the treatment of sporadic and familial ALS. It was initially developed by Brian Head, PhD’s lab at the University of California-San Diego and is licensed by Eikonoklastes. The therapy is produced by use of SynCav1, a first-in-class, non-monogenic gene therapy platform that uses precise, targeted overexpression of Caveolin-1 to treat a wide range of neurodegenerative diseases. Other indications Eikonoklastes is exploring using this platform for in preclinical trials include Alzheimer disease and traumatic brain injury, as well as Parkinson disease, Huntington disease, and multiple sclerosis in discovery studies.

“The ODD program is critical for incentivizing the development of new treatments for rare diseases, especially those like ALS with severe morbidity and mortality,” Samuel Lee, president and chief business officer, Eikonoklastes, added to the statement.1 “Achieving Orphan Drug Designation 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.

WATCH NOW: Clive Svendsen, PhD, on Astrocyte Progenitor Cell Therapy in ALS

The last couple of months half of 2022 has seen many updates in cell and gene therapy development for ALS. In September alone, Helixmith announced topline data from a phase 2a trial (NCT04632225) that showed that high-dose, repeated injections of Engensis, an intramuscularly delivered gene therapy, were found to be safe and well-tolerated in participants with ALS; the Cedars-Sinai allogeneic human neural progenitor cell therapy CNS10-NPC-GDNF demonstrated a manageable safety profile and produced glial cell line-derived neurotrophic factor in participants with ALS in a phase 1/2a study (NCT02943850); and the FDA cleared Cellenkos’ investigational new drug application for CK0803, a T regulatory cell therapy, that will soon be evaluated in a phase 1 study.2,3,4

Furthermore, in August 2022, Brainstorm Cell Therapeutics submitted a biologics license application (BLA) for its mesenchymal cell therapy NurOwn after a corrected statistical analyses of a phase 3 clinical trial (NCT03280056) revealed a statistically significant improvement on ALSFRS-R scores in participants with early-stage ALS.5 The FDA had previously advised against a BLA submission when the trial had previously not met its primary endpoint of responder rates on ALSFRS-R scores in all stages of disease progression.

“ALS is such a such a serious illness; you don't want to discard a treatment that might be potentially helpful. That's one of the worst things I think you could do. Maybe 10 years from now or 5 years from now, we might have so many treatments that maybe we wouldn’t need to pursue but I think we're still at the stage where anything that might help, we want to keep pursuing,” first author on the study Merit Cudkowicz, MD, chief, neurology, and director, Sean M. Healey & AMG Center for ALS, and Julieanne Dorn Professor of Neurology, Harvard Medical School, previously told CGTLive in an interview.

1. Eikonoklastes Therapeutics receives FDA orphan drug designation for 1st-in-class treatment of amyotrophic lateral sclerosis (ALS). News release. Eikonoklastes Therapeutics. November 9, 2022.
2. Helixmith announces topline results from phase 2a study of Engensis for treatment of ALS (amyotrophic lateral sclerosis). News release. Helixmith. September 6, 2022.
3. Baloh RH, Johnson JP, Avalos P, et al. Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial. Nat Med. Published online September 5, 2022.
4. Cellenkos receives FDA clearance of investigational new drug (IND) application for CK0803 for the treatment of amyotrophic lateral sclerosis (ALS). News release. Cellenkos. September 21, 2022.
5. BrainStorm Cell Therapeutics announces second quarter 2022 financial results and provides a corporate update. News release. BrainStorm Cell Therapeutics. August 15, 2022.
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