FDA Grants Orphan, Rare Pediatric Designations to Gene Therapies


LX1004 and APB-102 are currently in the early phases of research to treat CLN2 Batten disease and SOD1 amyotrophic lateral sclerosis, respectively.

R. Nolan Townsend

R. Nolan Townsend

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The FDA has granted rare pediatric disease designation to LEXEO Therapuetics' LX1004 for the treatment of CLN2 Batten disease and fast track designation to Apic Bio's APB-102 for the treatment of SOD1 amyotrophic lateral sclerosis (ALS), according to recent announcements.1,2

The gene therapies have different mechanisms of delivering action. On one hand, LX1004 is an AAV-mediated therapy that delivers CLN2 to the central nervous system (CNS), whereas APB-102 is a recombinant AAVrh10 vector that expresses an anti-SOD1 artificial microRNA. ABP-102 previously received orphan drug designation from the FDA, and most recently had its investigational new drug application cleared in April.

LX1004 for CLN2 Batten Disease

LEXEO Therapeutics has completed a Phase 1 clinical trial of LX1004 and plans to advance the program into pivotal studies in 2022.

“Both designations granted to LX1004 underscore the critical importance and urgency to advance new treatment approaches for CLN2 Batten disease, a fatal genetic disorder affecting the central nervous system,” said R. Nolan Townsend, chief executive officer, LEXEO Therapeutics, in a statement.1 “We are encouraged by the Phase I study results of LX1004 which reached clinical proof of concept, and we look forward to advancing the program through further clinical development with the hope of making it available for patients as soon as possible.” 

LEXEO is investigating gene therapies for other CNS disorders, such as APOE4 Alzheimer disease (AD), a program which is currently in phase 1 studies.3 Earlier phase programs include APOE4- / APOE2+ AD and R154S "Christchurch" AD.

APB-102 for SOD1 ALS

Apic Bio’s APB-102 expresses microRNA that binds to SOD1 mRNA, in turn reducing production of the mutant protein in patients with this form of the disease. Reducing mutant SOD1 protein levels may improve survival and function of motor neurons and potentially provide a therapeutic benefit to people with SOD1-linked ALS.

“We are pleased that the FDA recognizes the significant unmet need for treatments for SOD1 ALS, an always fatal neurogenerative disorder, where mutations in the SOD1 gene account for approximately one-fifth of all inherited forms of the disease,” said Jorge Quiroz, MD, MBA, executive vice president and chief medical officer, Apic Bio, in a statement.2 “We believe in the therapeutic potential of our gene therapy candidate APB-102 that targets the underlying pathophysiology of the disease, and we remain on track to initiate our Phase 1/2 study of APB-102 in early 2022.”

The Phase 1/2 clinical trial will be a multi-center, 3-part study to evaluate the safety, tolerability, and efficacy of intrathecally administered APB-102 in patients with SOD1 ALS mutations: part I, single ascending dose; part II, randomized, double-blind, placebo-controlled; and part III, extended follow-up. Apic Bio is approaching ALS from multiple angles, with their other candidates APB-104 (C9Orf72) and APB-105 (DF-SOD1) in earlier phases of research.4

"The clinical development of APB-102 is rooted in nearly 30 years of gene therapy research demonstrating the link between the 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,” said Robert Brown, DPhil, MD, professor, neurology, University of Massachusetts Medical School and scientific co-founder, Apic Bio, in a statement at that time.5

1. LEXEO Therapeutics receives rare pediatric disease designation and orphan drug designation for LX1004 for the treatment of CLN2 Batten disease. News release. LEXEO Therapeutics. July 28, 2021. Accessed August 4, 2021. https://finance.yahoo.com/news/lexeo-therapeutics-receives-rare-pediatric-123000141.html?guccounter=1
2. Apic Bio receives FDA fast track designation for APB-102 for the treatment of patients with SOD1 ALS. News release. Apic Bio. July 28, 2021. Acchttps://www.businesswire.com/news/home/20210728005193/en/Apic-Bio-Receives-FDA-Fast-Track-Designation-for-APB-102-for-the-Treatment-of-Patients-with-SOD1-ALS
3. Pipeline. LEXEO Therapeutics. 2020. Accessed August 4, 2021. https://www.lexeotx.com/pipeline
4. Pipeline. Apic Bio. 2020. Accessed August 4, 2021. https://apic-bio.com/pipeline/
5. 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 August 4, 2021. https://www.businesswire.com/news/home/20210421005318/en/Apic-Bio-Announces-FDA-Clearance-of-IND-Application-for-Lead-Gene-Therapy-Candidate-APB-102-for-the-Treatment-of-SOD1-ALS
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