Voyager hold adds to gene therapy woes

2020 has been a big year for gene therapy – for all the wrong reasons. The latest blow to the field was yesterday’s clinical hold on the phase II trial of Voyager and Neurocrine’s Parkinson’s disease candidate, NBIb-1817, following reports of MRI abnormalities in some participants. Restore-1 has not been recruiting subjects since April because of the Covid-19 pandemic, but warning signs have since emerged, with the companies saying in November that the data monitoring board had asked for a pause in dosing to evaluate brain imaging data. A similar issue hit Lysogene in June, with abnormalities seen on brain MRI scans in patients receiving its Sarepta-partnered gene therapy SAF302. NBIb-1817 and SAF302 are being developed for different indications, but both are delivered directly into the brain and both use an adeno-associated viral vector. Meanwhile, Sio Gene Therapies – formerly known as Axovant – has a Parkinson's gene therapy that is delivered to the brain, Axo-Lenti-PD. That project, which employs a lentiviral vector, has shown a clean safety profile so far. Voyager's stock sank 10% this morning. The latest news comes the same week as a safety scare with Uniqure’s etranacogene dezaparvovec.

Selected recently reported adverse events with gene therapies
Project Company Indication Vector used Adverse event(s) Date
NBIb-1817/VY-AADC Voyager Therapeutics/ Neurocrine Parkinson’s disease AAV2 MRI abnormalities Dec 2020
Etranacogene dezaparvovec Uniqure Haemophilia B AAV5 Liver cancer Dec 2020
Strimvelis Orchard Therapeutics ADA-SCID Gammaretroviral vector Leukaemia Oct 2020
AT132  Astellas (originated at Audentes) X-linked myotubular myopathy AAV8 Three deaths in pts with signs of liver dysfunction Aug 2020
LYS-SAF302 Lysogene/ Sarepta MPS type IIIA AAVrh.10 MRI abnormalities Jun 2020
SGT-001 Solid Biosciences  DMD AAV9  Complement activation Nov 2019*
*Clinical hold lifted Oct 2020. Source: company releases.

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