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Adrenomyeloneuropathy Natural History Study to Inform Gene Therapy Research

It will be the first AMN clinical study to utilize wearable technology for monitoring patient activity and outcomes.

CYGNET (NCT05008874), a multicenter natural history study to assess the disease progression of adrenomyeloneuropathy (AMN), is currently underway.1 Details of the study, which is being conducted by SwanBio, were presented at the 8th Congress of the European Academy of Neurology (EAN), June 25-28, 2022, in Vienna, Austria and virtual.

The study investigators will observe patients over the course of 2 years and will use wearable technology to track traditional motor tasks, novel activity, and sleep outcomes. Additionally, the study will track body sway, which has been associated with disease progression, and several other disease severity and functional impairment measures. SwanBio is hoping the data will be useful in informing future treatments for AMN, including its own SBT101, an AAV-based gene therapy candidate which is currently being investigated in PROPEL (NCT05394064), a phase 1/2 randomized, blinded, dose-escalation clinical trial.

“At SwanBio, our approach to drug development begins with deepening our understanding of the origin and trajectory of diseases like AMN, ideally enabling us to deliver gene therapies that are both highly effective and meaningful for the quality of life of patients. With this in mind, our proprietary CYGNET study was designed to better characterize AMN disease progression, which varies from person to person,” Steven Zelenkofske, DO, chief medical officer, SwanBio Therapeutics, said in a statement.1 “CYGNET is the first AMN clinical study to feature wearables, which may help us identify sensitive outcomes related to clinically relevant changes early in men with AMN.”

The CYGNET study, which has study locations both inside and outside of the US, will be open to male patients 18 years of age or older who have a confirmed diagnosis of adrenoleukodystrophy (ALD) and symptoms of AMN with no other major confounding comorbidities. The primary outcome measure will be disease progression, characterized by serial clinical evaluations of walking. A secondary outcome measure will evaluate the change over time in multiple quality of life parameters.

SwanBio anticipates that a total of 80 participants will enroll in the study. Over 40% of this amount had been enrolled by early June.

The ongoing PROPEL clinical trial is open to male patients aged 18 to 65 who have been diagnosed with X-linked ALD with a mutation in the ABCD1 gene confirmed through genetic testing and supported by observed elevated circulating VLCFA levels. The disease must additionally show clinical evidence of spinal cord involvement, but patients must still be independently ambulant. Patients who have evidence of or a past diagnosis of inflammatory cerebral disease will be excluded from the study, along with patients with a history of diabetes and patients who have previously received a gene therapy. The study will also not include patients for whom 15 years or more have passed since their initial onset of myeloneuropathy manifestations.

Patients will be randomly assigned to receive either a single intrathecal dose of SBT101 or sham procedure, with initial follow-up of 2 years. Patients who receive the study drug will be followed for safety outcomes for an additional 3 years, with patients who received the sham procedure eligible to receive SBT101 after the 2-year mark. The primary outcome measure for the study is safety and tolerability as measured by adverse events to SBT101. Secondary end points include disease progression, characterized by serial clinical assessments of walking ability measured by a 6-Minute Walk Test, and changes in quality of life, as indicated by questionnaires. A total of around 16 participants are anticipated to enroll.

REFERENCES
1. SwanBio presents design of innovative natural history study aimed to evolve understanding of adrenomyeloneuropathy and inform future treatments. News release. SwanBio Therapeutics. June 27, 2022. https://swanbiotx.com/investors-and-media/swanbio-presents-design-of-innovative-natural-history-study-aimed-to-evolve-understanding-of-adrenomyeloneuropathy-and-inform-future-treatments/