Following clinical hold lift, Astellas posts early Pompe gene therapy data
Fresh out of a clinical hold, Astellas is spotlighting data on its gene therapy for Pompe disease.
In four patients who got an infusion of the gene therapy, called AT845, three discontinued enzyme replacement therapy. As of the Sept. 15 cutoff, those three patients have been off enzyme replacement therapy for 19, 44 and 51 weeks, respectively.
Astellas did not bring any data on the primary efficacy endpoint — enzyme expression and activity — though it did present secondary efficacy data. The three participants who were taken off ERT maintained similar results in forced vital capacity, a measure of lung capacity, after stopping biweekly treatments. In addition, two of the three had consistent results on a six-minute walk test after being taken off ERT. The third saw a decrease in distance walked on the test after they developed a case of peripheral neuropathy.
The early-stage dose escalation trial is testing AT845 in adult late-onset Pompe disease patients. Two patients got a low dose of the therapy (3×1013 vg/kg), while two got a higher dose that was double that (6×1013 vg/kg). The one patient who remains on enzyme replacement therapy got the low dose, Astellas gene regulation leader Richard Wilson told Endpoints News.
AT845 is meant to deliver a copy of the gene for an enzyme called GAA via a viral vector to muscle tissues. People with Pompe lack the enzyme, leading to sugars building up and damaging the muscles. Currently, the standard of care for the genetic disease is a biweekly infusion of one of two enzyme replacement therapies — Myozyme/Lumizyme and its successor Nexviazyme — both developed by Sanofi’s Genzyme.
Astellas hopes its gene therapy can provide a longer-term treatment for the disease.
However, the gene therapy program was put on clinical hold in June after one of the high dose patients developed peripheral sensory neuropathy. That hold was lifted in late January. Upon lifting the hold, Astellas said that it was unable to conclude whether the neuropathy case was related to its drug.
Three of the four participants had high levels of liver enzymes, which have been seen in other gene therapies delivered via viral vectors as well. All three cases were resolved with changes to immune suppression, Astellas said.
The FDA told Astellas to continue dosing its next two patients at the higher dose of 6×1013 vg/kg, Wilson noted.
Wilson also pointed to results on a fatigue questionnaire, where three of the four patients saw their fatigue scores trend toward improvement. “This indicates an important fact that these patients have started to demonstrate some measures of feeling a little better,” he said. “I don’t want to mischaracterize that or over-promise it, but, from what we’re hearing from the PI, we feel that these improvements in fatigue are actually meaningful to patients.”
Wilson said that Astellas hopes to resume dosing in the coming weeks to months.
