Policy & Regulation
Additional Preclinical Data Supports Clinical Advancement of First AAV-Based Gene Therapy for Adrenomyeloneuropathy
18 May 2022 - - US-based gene therapy company SwanBio Therapeutics has presented additional details from studies of SBT101 in non-human primates and rodent models, the company said.

These data support the ongoing clinical advancement of SBT101 as a potential treatment for adrenomyeloneuropathy, a progressive, inherited, and debilitating neurodegenerative disease.

The SBT101 preclinical data, presented at the American Society of Gene and Cell Therapy (ASGCT) 2022 annual meeting in Washington, DC, demonstrate dose-dependent functional improvement as measured by grip strength in a mouse model of AMN.

Additional details from previously reported studies on efficacy, biodistribution, and safety data also support the dosing strategy SwanBio will be implementing in its upcoming Phase 1/2 study, expected to initiate by the end of the year.

The underlying cause of AMN is a deficiency in the ABCD1 gene, which disrupts the function of cells in the spinal cord and other tissues, leading to the accumulation of very long-chain fatty acids (VLCFAs) within affected organs, nerve degeneration and often adrenal gland dysfunction, causing the symptoms of the disease.

These symptoms include loss of mobility in adulthood, incontinence, debilitating pain, and sexual dysfunction, which all negatively impact quality of life. SBT101 is designed to increase ABCD1 expression and address the root cause of the disease.

In mouse models of AMN, intrathecal delivery of SBT101 demonstrated dose-dependent improvements in both disease markers and functional endpoints:

Four-paw grip strength was significantly improved at 7-8 months after administration. Grip strength was maintained 10-11 months after SBT101 administration.

VLCFA levels in the lumbar spinal cord tissue were reduced at post-mortem evaluation approximately 10-11 months after SBT101 administration.

hABCD1 messenger RNA expression was detected in the lumbar, thoracic, and cervical spinal cord at post-mortem evaluation approximately 10-11 months after SBT101 administration.

In all mouse model and NHP studies, IT administration of SBT101 was well tolerated at doses predicted to be clinically relevant in people with AMN, and no drug-associated adverse events were noted.

In NHPs, biodistribution studies following IT delivery of SBT101 demonstrated dose-dependent presence of AAV9 vector genomes and hABCD1 mRNA in target tissues.

It also demonstrated extended administration (a 24-hour infusion time) of AAV9 provided more widespread transduction of AMN target tissues (spinal cord and dorsal root ganglia) as compared to bolus administration.

A six-hour administration was shown to be equivalent to the extended infusion time in terms of delivering widespread distribution of AAV9 vector to AMN target tissues.

SBT101 is the first AAV-based gene therapy candidate cleared by the FDA for human studies, designed to compensate for the disease-causing ABCD1 mutation in people living with adrenomyeloneuropathy.

In preclinical studies, treatment with SBT101 demonstrated dose-dependent improvement of disease markers and functional improvement in AMN mouse models.

SBT101 was also shown to be well-tolerated in non-human primates at six months post-treatment.

The clinical program for SBT101 builds on this positive preclinical data, plus the company's deep understanding of the underlying pathophysiology of the disease and the patient experience of AMN, including new insights being gathered in an ongoing, proprietary natural history study, CYGNET.

SwanBio said it expects to initiate a randomized, controlled Phase 1/2 clinical trial designed to assess the safety and efficacy of SBT101 in patients with AMN in the second half of 2022. In early 2022, the FDA cleared SwanBio's Investigational New Drug application for SBT101 and granted SBT101 Fast Track and Orphan Drug Designation.

Adrenomyeloneuropathy is a progressive and debilitating neurodegenerative disease caused by mutations in the ABCD1 gene that disrupt the function of spinal cord cells and other tissues.

AMN is characterized by loss of mobility in adulthood, incontinence, pain, and sexual dysfunction which all affect quality of life.

Between 8,000-10,000 men in the United States and European Union are living with AMN. There are no approved therapies for the treatment of the disease; current standard of care is limited to symptom management.

SwanBio Therapeutics is a gene therapy company that aims to bring life-changing treatments to people with devastating, inherited neurological conditions.

SwanBio is advancing a pipeline of gene therapies, designed to be delivered intrathecally, that can address targets within both the central and peripheral nervous systems.