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Adrenomyeloneuropathy Gene Therapy Trial Begins

The trial will incorporate findings from CYGNET, a natural history study designed to assess the disease progression of AMN.

SwanBio Therapeutics has announced the initiation of the phase 1/2 PROPEL clinical trial (NCT05394064) for SBT101, an investigational gene therapy intended to treat adrenomyeloneuropathy (AMN).1

SBT101 is intended to deliver a functional copy of the human adenosine triphosphate (ATP)-binding cassette transporter subfamily D member 1 gene (hABCD1) via a recombinant adeno-associated virus serotype 9 (AAV9) vector. The multinational, randomized, blinded, dose-escalation PROPEL study will evaluate the safety and efficacy of the therapy for male patients aged 18 to 65 who have been diagnosed with X-linked adrenoleukodystrophy (ALD) with a confirmed mutation in the ABCD1 gene.

The trial will incorporate findings from CYGNET (NCT05008874), a multinational natural history study designed to assess the disease progression of AMN.1,2 CYGNET includes the observation of participants over the course of 2 years and is using wearable technology to track traditional motor tasks, novel activity, and sleep outcomes. The study is also tracking body sway and several other disease severity and functional impairment measures. CYGNET includes male patients aged 18 years and older who have a confirmed diagnosis of ALD and symptoms of AMN with no history of cerebral inflammatory disease and no other major confounding comorbidities. Participants are additionally required to show evidence of spinal cord involvement and to have an Expanded Disability Status Scale score of 1 to 6.5. As of December 13, 2022, the trial had enrolled 65 participants, and is no longer recruiting new patients.

“As we wrap up a pivotal year for SwanBio, I am pleased to announce that we have successfully initiated PROPEL, our first interventional clinical study,” Tom Anderson, chief executive officer and director, SwanBio, said in a statement.1 “This milestone comes on the heels of completing enrollment and over-subscribing our natural history study, CYGNET. These 2 achievements not only demonstrate Swan’s ongoing commitment to the AMN community, but also highlight the exceptional creativity and execution capabilities of our team. We expect to dose the first patient in PROPEL in early 2023 and are well positioned to meet our recruitment goals for this trial.”

The investigational new drug application for SBT101 was originally cleared by the FDA in February of this year.3 The decision was based on the results of preclinical research, data from which was presented in October 2021 at the European Society for Gene and Cell Therapy (ESGCT) Virtual Congress.4 The preclinical research showed dose-dependent expression of hABCD1 and a reduction of VLCFA levels in mouse models.1,4 The therapy was also shown to be well-tolerated in non-human primates through 6 months after treatment. Additional preclinical data was presented at the American Academy of Neurology (AAN) 2022 Annual Meeting in April.5 SBT101 received fast track designation from the FDA in February 2022 and orphan drug designation in March 2022.6,7

REFERENCES
1. Swanbio Therapeutics initiates first-in-human study of AAV gene therapy for adrenomyeloneuropathy. News release. SwanBio Therapeutics. December 15, 2022. https://swanbiotx.com/investors-and-media/swanbio-therapeutics-initiates-first-in-human-study-of-aav-gene-therapy-for-adrenomyeloneuropathy/ 
2. 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/ 
3. SwanBio Therapeutics Announces FDA investigational new drug clearance for first AAV-based gene therapy for the treatment of adrenomyeloneuropathy. News release. SwanBio Therapeutics. January 25, 2022. https://www.businesswire.com/news/home/20220125005388/en/SwanBio-Therapeutics-Announces-FDA-Investigational-New-Drug-Clearance-for-First-AAV-Based-Gene-Therapy-for-the-Treatment-of-Adrenomyeloneuropathy 
4. SwanBio Therapeutics announces new preclinical data demonstrating proof of principle for SBT101 gene therapy as a potential treatment of adrenomyeloneuropathy. News release. SwanBio Therapeutics. October 19, 2021. https://swanbiotx.com/investors-and-media/swanbio-therapeutics-announces-new-preclinical-data-demonstrating-proof-of-principle-for-sbt101-gene-therapy-as-a-potential-treatment-of-adrenomyeloneuropathy/
5. Updated preclinical data supportpotential of first AAV-based gene therapy as a treatment for adrenomyeloneuropathy. News release. SwanBio Therapeutics. April 5, 2022. https://swanbiotx.com/investors-and-media/updated-preclinical-data-support-potential-of-first-aav-based-gene-therapy-as-a-treatment-for-adrenomyeloneuropathy/ 
6. FDA grants fast track designation to SBT101, the first investigational AAV-based gene therapy for patients with adrenomyeloneuropathy (AMN). News release. SwanBio. February 16, 2022. https://www.businesswire.com/news/home/20220216005313/en/FDA-Grants-Fast-Track-Designation-to-SBT101-the-First-Investigational-AAV-Based-Gene-Therapy-for-Patients-With-Adrenomyeloneuropathy-AMN 
7. FDA grants orphan drug designation to SBT101, the first investigational AAV-based gene therapy for adrenomyeloneuropathy (AMN). News release. SwanBio Therapeutics. March 15, 2022. https://www.biospace.com/article/releases/fda-grants-orphan-drug-designation-to-sbt101-the-first-investigational-aav-based-gene-therapy-for-adrenomyeloneuropathy-amn-/