The gene therapy uses an AAV vector to restore healthy levels of the alpha-galactosidase enzyme, which is rendered dysfunctional in patients with Fabry disease, leading to the toxic build-up of lipids in cells.
UniQure has suspended dosing in two arms of a mid-stage Fabry disease study for its gene therapy AMT-191 after detecting cases of liver enzyme elevations.
The pause, buried in a news release on Friday, will apply to the mid- and high-dose groups of a Phase 1/2a trial, who were infused with 4x1013 genome copies per kilogram (gc/kg) and 6x1013 gc/kg of AMT-191, respectively. Two patients in the mid-dose cohort developed grade 3 liver enzyme elevations—cases that were severe or medically significant but not life-threatening. These cases were deemed dose-limiting by an independent data panel, and UniQure elected to pause dosing per the study’s protocol.
Both patients have received and responded to corticosteroid therapy.
UniQure announced that it had not detected any serious adverse events in the study’s low-dose cohort, which was given 2x1013 gc/kg of the gene therapy. But it did not explicitly say that dosing of that group will continue as planned.
Efficacy data released Friday suggest that AMT-191 exerts a therapeutic benefit on alpha-galactosidase A, a key enzyme that is dysfunctional in Fabry disease, leading to a buildup of lipids in cells across the body, triggering the multi-system disorder.
In particular, uniQure detected dose-dependent improvements in alpha-galactosidase A. Enzyme activity reached 0.34- to 82.2-fold above normal levels at the lowest dose and 27.7- to 223.7-fold at the highest dose. These elevations persisted throughout the observation period, the biotech said. Ultimately, six of 11 dosed patients were able to stop enzyme replacement therapy.
Writing to investors on Friday afternoon, analysts at William Blair called these efficacy data “an incremental positive” for uniQure, pointing to AMT-191’s “durability of expression and efficacy.” Still, the firm awaits more data for the gene therapy, particularly regarding the estimated glomerular filtration rate, a surrogate endpoint that can be used to support a regulatory filing.
The Phase 1/2a study is ongoing. Preliminary results “are supportive of the potential for AMT-191 as a one-time administered gene therapy for people living with Fabry disease,” CMO Walid Abi-Saab said in a statement on Friday. The company has yet to provide a detailed roadmap of when it expects to release more data for the asset.
