Updated, six-month data from a Phase 1/2 trial show a continued drop in the levels of two disease biomarkers in the first patient given a single infusion of AVR-RD-02, Avrobio’s experimental gene therapy for Gaucher disease type 1, the company announced.
Results obtained by Jan. 4, the cutoff date marking six months post-treatment, also continued to show a positive safety profile, without serious or unexpected adverse side effects related to AVR-RD-02.
The open-label trial (NCT04145037), called GuardOne, is underway at one site in Australia and one in Canada, and enrolling up to 16 patients, ages 16–35, with a confirmed diagnosis of Gaucher type 1 and stable disease.
The company also announced new positive data across its gene therapy programs for Fabry disease and cystinosis, two diseases that, like Gaucher, are characterized by the buildup of toxic substances inside lysosomes, the structures responsible for the breakdown and recycling of cellular products.
“We are thrilled to begin the new year with this update, which adds to the breadth of strong clinical data we’ve reported across our leading lysosomal disorder pipeline of single-dose gene therapies,” said Geoff MacKay, the president and CEO of Avrobio.
“With 13 patients dosed across three clinical programs, we have observed sustained and potentially transformative improvements in key biomarkers and functional metrics,” he added.
AVR-RD-02, designed using Avrobio’s plato platform, uses a harmless lentiviral vector as a vehicle to deliver a working copy of the GBA gene — faulty in people with Gaucher — to patients’ own blood cell precursors, called hematopoietic stem cells. These cells are isolated from the patient, modified in the lab, and then infused back to the person.
The gene therapy aims to permanently restore the production of the beta-glucocerebrosidase — the enzyme produced from the GBA gene — lowering the accumulation of fatty toxic substances inside cells.
Participants in GuardOne will be followed for over one year after dosing. The first treated patient discontinued ERT one month after receiving AVR-RD-02, and remains free of a need for ERT.
Newest data showed that the blood levels of chitotriosidase — a biomarker of activated immune cells called macrophages and the cause of chronic inflammation — continue to drop, reaching a 49% reduction compared with the start (baseline) of the study, when the patient was still using ERT. At three months post-therapy, these levels had dropped 17%.
According to Avrobio, this suggests that healthy macrophages with the therapeutic gene may be replacing the activated macrophages, also known as Gaucher cells.
In addition, the patient’s levels of glucosylsphingosine (lyso-Gb1), a Gaucher biomarker associated with organ damage, fell by 44% from baseline at six months, after a reduction of 22% seen three months after treatment.
Levels of hemoglobin — the protein responsible for carrying oxygen in red blood cells — and platelet counts, which tend to be low in people with Gaucher, remained within a normal range over the six months.
“The early data from the first patient dosed with AVR-RD-02, our investigational gene therapy for Gaucher disease type 1, are consistent with what we have seen in our Fabry disease trials,” MacKay said.
“Based on the data observed to date, we believe lentiviral gene therapy drives down toxic metabolites below levels of ERT, supporting our view that gene therapy has the potential to prevent, halt or even reverse progression of these devastating diseases with a single infusion,” he added.