Sangamo Therapeutics has presented updated preliminary data from its phase 1/2 Fabry disease clinical trial, revealing that recipients of its gene therapy had elevated levels of a key enzyme even after stopping taking the standard of care.
When Sangamo shared data on its AAV2/6 gene therapy isaralgagene civaparvovec, also known as ST-920, earlier this year, four of the six subjects were on enzyme replacement therapy (ERT). All four subjects subsequently stopped receiving ERT and, as of the latest data cutoff, had been off the therapy for between six and 28 weeks. In all four subjects, levels of α-Gal A, the enzyme at the root of Fabry disease, remained elevated.
While the top-line finding is that α-Gal A levels stayed above the mean normal level in all subjects, there was considerable patient-to-patient variation. In subject one, enzyme activity went from 12.4-fold above normal in the earlier analysis to 30-fold above normal in the latest cut of data.
However, α-Gal A activity trended downward in some other patients, sliding from 10.3-fold to 7.9-fold in subject four and from 16.7-fold to 14.7-fold in subject five. The decline predated the end of ERT therapy in subject five, who only stopped treatment six weeks before the data cutoff. But activity fell in subject four, the first patient to come off ERT, after the enzyme treatment was stopped.
The biotech also saw declines in activity in two ERT pseudo-naïve subjects. As ST-920 is intended to be a one-time treatment, the durability of its effects will be a key data point as it moves toward and potentially onto the market.
Sangamo is gearing up to deliver the data regulators will demand to approve the gene therapy. The latest data drop features results for three more patients, including the first two enrolled at the fourth dose. All the new patients have elevated α-Gal A levels, and the worst adverse event was grade 2 fever.
Buoyed by the data, the biotech has kicked off the expansion phase of the study, dosing four patients. The expansion phase includes the first female patient in the study. In parallel, Sangamo is planning for a potential phase 3 study of its gene therapy.