Gene Therapy Showing Efficacy Years After Use in Clinical Trials, Avrobio Says

With data now reaching up to 3.5 years, benefits are continuing to be reported with the use of AVR-RD-01, Avrobio‘s experimental gene therapy for Fabry disease, in Phase 1 and 2 clinical trials, the company announced.

Avrobio plan to meet with the U.S. Food and Drug Administration (FDA) to discuss possibly requesting accelerated approval for the investigational therapy.

“With our Fabry disease data continuing to reflect sustained and durable results, with our first patient now out 3.5 years from dosing, we are planning our strategy to seek accelerated approvals in one or more major markets,” Geoff MacKay, president and CEO of Avrobio, said in a press release.

Fabry disease is caused by mutations in the gene GLA, resulting in a lack of functional alpha-galactosidase A (AGA), an enzyme needed to break down the fatty substance globotriosylceramide (Gb3). The lack of working AGA causes Gb3 to accumulate in cells, leading to cell and tissue damage.

AVR-RD-01 is a cell-based therapy in which a patient’s hematopoietic stem cells — the stem cells that produce blood and immune cells — are genetically modified so they can produce a functional version of the AGA enzyme. An engineered viral vector is used to introduce a non-mutated version of the GLA gene to these cells before they are returned to the patient.

Two ongoing clinical trials are evaluating AVR-RD-01 in people with Fabry disease: a Phase 1 investigator-sponsored trial called FACTs (NCT02800070), and a Phase 1/2 trial called FAB-201 (NCT03454893) sponsored by Avrobio.

Enrollment in these trials was paused earlier this year in response to the COVID-19 pandemic, with enrollment resuming as individual hospitals allowed. FAB-201 is currently enrolling males, ages 16 to 50, at sites in the U.S., Australia, and Canada; more information is available here.

According to Avrobio, data from these trials continue to support AVR-RD-01’s use raising the levels of functional AGA and decreasing those of Gb3. The results suggest that the modified cells are successfully engrafting in patients’ bodies, allowing for the production of the functional enzyme.

Trial data also suggest that participants have generally stable kidney function, as assessed by estimated glomerular filtration rate (eGFR). Typically, untreated Fabry patients experience a faster-than-normal decline in kidney health.

“Avrobio believes the stability in eGFR for patients in its clinical trials to be clinically significant and relevant,” the company’s release stated.

No unexpected safety events have been reported in either trial. There have been eight serious adverse events reported, all of which are thought to be due to factors like the underlying disease, or the regimens used to condition the body before introducing the modified cells. In a few trial participants, low levels of antibodies against AGA have been detected.

AVR-RD-01 has been designated an orphan drug in both the U.S. and Europe, supporting its development.