ALS001 Receives Orphan Drug Designation for Amyotrophic Lateral Sclerosis


The autologous, expanded Treg cell therapy was found safe and tolerable in a phase 1 study of 3 patients with ALS.

Stanley H. Appel, MD, codirector, Houston Methodist Neurological Institute; chair, department of neurology and the Peggy and Gary Edwards Distinguished Chair in ALS, Houston Methodist Hospital; professor of neurology, Weill Cornell Medical College

Stanley H. Appel, MD

The FDA has granted orphan drug designation to ALS001, and investigational agent from Coya Therapeutics, for the treatment of amyotrophic lateral sclerosis (ALS). ALS progression may be connected to dysfunctional and decreased levels of autologous regulatory T cells (Tregs), necessitating expanded Treg cell therapy. 

ALS001 is currently in an ongoing phase 2a trial (NCT04055623), with data anticipated by the end of summer 2021. The randomized, placebo-controlled trial will assess the tolerability of regulatory Tregs taken and expanded outside of the body, then reinserted intravenously (IV) with subcutaneous low-dose interleukin-2 (IL-2). 

“The orphan drug designation for ALS001 underscores the medical need that exists for patients with ALS,” Howard Berman, PhD, CEO, Coya Therapeutics, said in a statement. “Although there are currently no meaningful treatments for these patients, we are excited by our preclinical and early clinical data demonstrating ALS001’s ability to harness the neuro-protective effects of Treg cell therapy—ultimately slowing and halting the progression of ALS…We look forward to showcasing our manufacturing scalability, optimizing our clinical development plans, and working with the FDA to bring ALS001 to patients as efficiently and quickly as possible.”

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Autologous infusions of expanded Tregs in ALS patients were found both safe and tolerable in a phase 1 trial (n = 3), and patients reported no infusion-related adverse events. Presentations were given at a webinar hosted by Coya Therapeutics in June 2021, outlining the therapeutic potential of ALS001 to slow or halt disease progression of ALS. A presentation on phase 1 findings was given by Stanley H. Appel, MD, codirector, Houston Methodist Neurological Institute; chair of the department of neurology and the Peggy and Gary Edwards Distinguished Chair in ALS, Houston Methodist Hospital; and professor of neurology, Weill Cornell Medical College. 

During his presentation, Appel summarized results from the phase 1, open-label pilot study, which found that during infusions of autologous expanded Tregs with concomitant subcutaneous injections of IL-2, Treg numbers increased, maximal inspiratory pressure (respiratory function) was stabilized, and notably, patients halted disease progression. Additionally, investigators saw enhanced Treg suppressive function, which correlated with the slowing of clinical decline.

“We had no negative changes and no clinically significant ‘bad guys,’ no EKG [electrocardiography] changes, and all patients noted an increase of frequency, intensity, of jumping of the muscles—and that means that the nerves connected to the muscles were functioning,” Appel said during his presentation. 

Dosing of another investigational treatment, WVE-004, in patients with C9orf72-associated ALS (C9-ALS) and frontotemporal dementia (C9-FTD), also recently began. Developed by Wave Life Sciences, the treatment seeks to identify ideal dose level and frequency in patients with C9-ALS and C9-FTD.

WVE-004 is a stereopure antisense oligonucleotide designed to target variants containing G4C2, a hexanucleotide repeat expansion associated with the C9orf72 gene. As one of the most common genetic causes of ALS and FTD, both sporadic and inherited, expansion of G4C2 in C9orf72 may cause increased repeat-containing RNA transcripts and abnormally translated dipeptide repeat proteins (DPRs), further leading to neurotoxicity and insufficient C9orf72 protein levels.

The global, multicenter, randomized, double-blind, placebo-controlled trial will assess safety and tolerability of single- and multiple-ascending intrathecal doses of WVE-004, with additional clinical data expected to be generated through 2022.

1. Coya Therapeutics receives orphan drug designation from the FDA for ALS001, an autologous treg cell therapy, for the treatment of ALS. News Release. Coya Therapeutics. July 7, 2021. Accessed August 10, 2021.
2. Appel, SH (2021, June 11). Coya Therapeutics, Inc. KOL Webinar on ALS001 for the Treatment of Amyotrophic Lateral Sclerosis (ALS) featuring Dr. Stanley Appel (Houston Methodist Neurological Institute).
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