FDA Approves Avrobio’s Gene Therapy Program for Fabry Disease

The U.S. Food and Drug Administration (FDA) has approved Avrobio’s clinical program for AVR-RD-01 as a gene therapy candidate for the treatment of Fabry disease.

Supported by the FDA’s decision, AvroBio will expand patient recruitment for its Phase 2 FAB-201 clinical trial (NCT03454893) to include patients across the United States. Recruitment is set to begin in the second half of this year. Information on recruitment and site locations will be made available at the trial’s page.

“We are very pleased that FAB-201 remains on track to expand into sites in the U.S. in the second half of 2019,” Geoff MacKay, president and CEO of Avrobio, said in a press release.

In the ongoing FAB-201 Phase 2 trial, researchers are evaluating AVR-RD-01’s efficacy and safety in eight to 12 previously untreated male patients age 16 or older.

The trial is broken into five periods: an initial screening, baseline assessment, pre-transplant period in which patients will receive treatment for four weeks to destroy their blood stem cells (a process called  myeloablation), gene therapy administration, and post-transplant follow-up for 48 weeks. Once the study is completed, patients will be followed for up to 15 years to monitor the therapy’s efficacy and safety.

AvroBio also aims to incorporate into the FAB-201 trial its newly developed plato platform, which was optimized to facilitate and control gene-therapy delivery.

“Importantly, we believe this U.S. FDA clearance represents a major milestone as we transition to plato, our optimized commercial-scale platform for our anticipated future worldwide commercialization activities. We have now achieved initial regulatory clearances for clinical trials in Australia, Canada, and the U.S. which incorporate our plato platform,” MacKay said.

AVR-RD-01 is a gene therapy that uses blood progenitor cells, also known as hematopoietic stem cells, to produce a functional alpha-galactosidase A (AGA) enzyme, which is deficient in Fabry disease. A modified, harmless viral vector carrying a functional version of GLA gene — which encodes the AGA enzyme — is introduced into the stem cells collected from the patient before they are re-infused.

AVR-RD-01’s safety is being tested in an investigator-sponsored Phase 1 trial (NCT02800070) in up to six patients who have been treated with standard enzyme replacement therapy (ERT) for at least six months.

Up until February 2019, six patients had been treated with AVR-RD-01 gene therapy — four in the Phase 1 and two in the Phase 2 trials.

Early data has shown that all four patients who reached three months or longer after receiving AVR-RD-01 — three of whom are in the Phase 1 study — had higher activity of AGA in the blood at all time points compared to males with classic Fabry disease. 

The levels of lyso-Gb3, a byproduct of the fatty molecules that accumulate inside cells of people with Fabry disease, had decreased in three patients — one patient in the Phase 1 study and two in the Phase 2 trial.

Specifically, the patient in the FAB-201 trial experienced an 85% reduction in lyso-Gb3 levels at six months, from 202 nmol/hr/ml to 31 nmol/hr/ml.

One of the patients in the Phase 1 study showed sustained decreases in plasma lyso-Gb3 levels from month 3 and up to 22 months of treatment, after stopping ERT at month 18. The other patient, who chose not to resume ERT after starting treatment with AVR-RD-01, demonstrated a reduction of lyso-Gb3 from 52 nmol/hr/ml to 33 nmol/hr/ml at three months.

According to the company, meaningful changes in lyso-Gb3 levels could reflect the efficacy of AVR-RD-01 as these patients did not have potential confounding effects from ERT.

Safety results suggest that AVR-RD-01 is well-tolerated without any serious adverse events.