FDA Clears IND Application for SOD1-ALS Gene Therapy


Apic Bio plans to initiate a phase 1/2 clinical trial in late 2021 or early 2022 as a multi-center, 3-part study to evaluate APB-102 in patients with SOD1-ALS mutations.

John Reilly

John Reilly

Apic Bio recently announced that the FDA has given clearance to an investigational new drug (IND) application for APB-102, the company’s gene therapy candidate to treat patients with SOD1-mutated amyotrophic lateral sclerosis (ALS).1

In preclinical proof of concept studies, APB-102 was shown to slow or reverse progression of SOD1-ALS though a next generation recombinant adeno-associated virus (AAV) capsid and micro ribonucleic acid (microRNA) vector construct. “FDA IND clearance for our drug candidate APB-102 to treat SOD1-ALS is a significant milestone for Apic Bio and takes us 1 step closer to bringing potentially disease-modifying therapies to patients with genetic diseases,” John Reilly, chief executive officer and co-founder, Apic Bio, said in a statement.

Additional data from an SOD1-ALS mouse model showed that silencing of SOD1 using APB-102 prolonged survival by approximately 50 days and delayed weight loss and limb weakness in treated animals compared to untreated controls. Although SOD1 suppression improved breathing and prolonged survival, it did not ameliorate the restrictive lung phenotype.2

The gene therapy is designed so that the microRNA binds to SOD1 mRNA thereby reducing production of protein which is mutant in patients with this form of the disease. Reducing SOD1 protein levels may improve survival and function of motor neurons and potentially provide a therapeutic benefit to patients with SOD1 induced ALS.1

READ MORE: Magnetic Resonance’s Impact on Diagnosis, Prognostication, and Therapeutic Approaches in Neuromuscular Disorders

Apic Bio plans to initiate a multi-center, 3-part phase 1/2 clinical trial in late 2021 or early 2022 to evaluate the safety, tolerability, and efficacy of intrathecally administered APB-102 in patients with SOD1-ALS mutations. Part 1 will be a single ascending dose study, while Part 2 will be the randomized, double-blind, placebo-controlled trial. Part 3 is an extended follow-up.

"The clinical development of APB-102 is rooted in nearly 30 years of gene therapy research demonstrating the link between SOD1 gene mutation and ALS and the strong potential of AAV-delivered SOD1 targeting miRNA to slow down or reverse the progression of ALS in patients with SOD1 mutations,” Robert Brown, DPhil, MD, professor of neurology, University of Massachusetts Medical School, and scientific co-founder, Apic Bio, said in a statement. “Despite SOD1 gene mutations being well understood as a cause of genetic ALS for decades, we don’t yet have an approved treatment option that targets the disorder at the source. I am pleased to see APB-102 progress as Apic Bio aims to develop a meaningful, long-term disease modifying gene therapy option for patients.”

Brown was a lead member of the team that discovered SOD1 as the first genetic mutation linked to ALS. Approximately 10% of ALS cases have a known genetic driver. Of that 10%,, approximately 20% are linked to a mutation in the SOD1 gene that codes for the enzyme superoxide dismutase 1.1 In June 2019, the FDA granted orphan drug designation to APB-102 for the treatment of SOD1-ALS. Currently, riluzole (Rilutek; Sanofi) and edaravone (Radicava; Mitsubishi Tanabe Pharma America) are the only 2 FDA approved treatments for patients with ALS.

1. Apic Bio announces FDA clearance of IND application for lead gene therapy candidate APB-102 for the treatment of SOD1 ALS. News release. Apic Bio. April 21, 2021. Accessed April 28, 2021. https://apic-bio.com/apic-bio-announces-fda-clearance-of-ind-application-for-lead-gene-therapy-candidate-apb-102-for-the-treatment-of-sod1-als/
2. Keeler AM, Zieger M, Sample C, et al. Intralingual and intrapleural AAV gene therapy prolongs survival in a SOD1 ALS mouse model. Mol Ther Methods Clin Dev. Published online June 12, 2020. doi: 10.1016/j.omtm.2019.12.007
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