uniQure has announced updated preliminary safety and exploratory efficacy data from 11 patients in its phase 1/2a trial of AMT-191, an investigational AAV gene therapy for the treatment of Fabry disease. The updated data was presented at the WORLDSymposium in San Diego, California.
As of the study data cutoff date, all 11 patients in the three dose cohorts (6×1013 genome copies/kilogram (gc/kg), 4×1013 gc/kg and 2×1013 gc/kg) had elevated α-galactosidase A (α-Gal A) activity.
Importantly, dose-dependent elevations were observed across the three dose levels with α-Gal A activity ranging from 0.34- to 82.2-fold above mean normal level1 at the lowest dose, 1.6- to 312.52-fold at the mid dose, and 27.7- to 223.7-fold at the highest dose.
These increases were durable for the measured time-period ranging from the longest follow-up period of more than a year in a treated patient (high-dose cohort) to the shortest follow-up period of four months in a treated patient (mid-dose cohort).
Six of 11 dosed patients were withdrawn from enzyme replacement therapy (ERT) having met a pre-specified criteria including elevated α-Gal A activity. Stable plasma lyso-Gb3 levels were maintained post-dose across all dose cohorts, regardless of ERT status through the cutoff date.
AMT-191 continued to show a manageable safety profile. No Serious Adverse Events (SAEs) related to AMT-191 have been observed at the 4×1013 gc/kg and 2×1013 gc/kg doses. Two patients at the 4×1013 gc/kg dose experienced asymptomatic grade 3 liver enzyme elevations.
Both were confirmed as dose-limiting toxicity following an Independent Data Monitoring Committee review, and per protocol, the company has paused additional dosing in the mid- and high-dose cohorts pending further evaluation. Both patients have responded to corticosteroid therapy and remain in follow up.
No additional SAEs have been observed at the 6×1013 gc/kg dose beyond the five previously reported in two patients: two SAEs unrelated to AMT-191 (stroke, diplopia), two related SAEs (chest pain, increased troponin), and one possibly related SAE (leptomeningeal enhancement).
As previously reported, one patient at the 6×1013 gc/kg dose experienced an asymptomatic, grade 3 liver enzyme elevation that fully resolved with a limited course of corticosteroid therapy.
AMT-191 has been granted both Orphan Drug and Fast Track designation by the US Food and Drug Administration.
