Avrobio Stopping Its Gene Therapy Program for Fabry Disease

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

Share this article:

Share article via email
AVR-RD-01 gene therapy | Fabry Disease News | clinical trials illustration

Note: This story was updated Jan. 17, 2022, to note that Avrobio is deprioritizing its Fabry program.


Avrobio is stopping its gene therapy program for Fabry disease in favor of clinical programs for other disorders, including cystinosis and Gaucher disease type 1.

According to a company press release, increasing challenges in the market and regulatory environment for Fabry disease accompanied by recent clinical trial data showing variable responses among patients, which would extend the program’s development, were the reasons behind this decision.

The company will cease enrollment for the FAB-GT Phase 2 trial, currently testing the safety and effectiveness of a single-dose of Avrobio’s investigational gene therapy AVR-RD-01 in people with Fabry disease.

“We’re fully aware of the impact this difficult decision has on the patients and families whom we have had the privilege to get to know over the years, but we believe deprioritizing and halting enrollment in our Fabry disease program is the right step forward for Avrobio and preserves our ability to continue developing therapies with the potential to address urgent unmet needs in the lysosomal disorder community,” said Geoff MacKay, Avrobio’s president and CEO.

Fabry is caused by mutations in the GLA gene, resulting in a lack of functional alpha-galactosidase (AGA), an enzyme needed to break down the fatty compound globotriosylceramide (Gb3). AVR-RD-01 is a one-time therapy that aims to deliver a working version of this gene to a patient’s hematopoietic stem cells (HSCs) — cells present in the bone marrow that can give rise to different types of blood cells.

Recommended Reading
Jasper and Avrobio | Fabry Disease News | JSP191 | illustration of handshake

Jasper Therapeutics, Avrobio Team Up to Assess JSP191

With AVR-RD-01, HSCs are first collected from a patient in a procedure called apheresis, and exposed to the viral vector that is used to deliver the functional GLA gene to the cells. The patient then undergoes a procedure called conditioning to destroy bone marrow cells and “make room” for the modified stem cells, returned to the patient as a transplant — a process called engraftment.

Two clinical trials were evaluating the safety and effectiveness of AVR-RD-01 in people with Fabry disease: a Phase 1 (NCT02800070) in five men over a period of five years, and the Avrobio-sponsored FAB-GT Phase 1/2 trial (NCT03454893) which has dosed nine patients to date who have not received prior treatment within three years.

In November, at the 14th International Congress of Inborn Errors of Metabolism, held in Sydney, Australia, researchers revealed that AVR-RD-01 continued to show a positive safety profile in its clinical trials, with no serious adverse events related to the treatment reported.

Safety data presented covered 13 Fabry patients given the therapy in one of the two clinical trials — eight patients in FAB-GT, and five patients in the Phase 1 trial. No serious side effects directly related to treatment with AVR-RD-01 were reported in any patient.

At the time, preliminary safety results on a ninth person in the FAB-GT trial also supported the therapy’s overall safety profile.

Previous data from these trials showed an increase in AGA activity following infusion with AVR-RD-01.

However, combined data from the five most recently dosed patients in the FAB-GT trial showed variable results, Avrobio reported in its Jan. 4 release. In three patients, the activity levels of AGA enzyme in blood cells (leukocytes and plasma cells) dropped rapidly — after three to nine months — reaching almost the levels seen at the start of the trial (baseline).

Moreover, these patients showed a reduction in the number of blood cells carrying the healthy version of the GLA gene within three to nine months after treatment.

“Previously reported data from 13 patients treated across our three clinical-stage programs have shown durable engraftment out 9 to 54 months. It is the new data from the five most recently dosed Phase 2 FAB-GT patients that are discordant with these other data and show variable engraftment,” MacKay said.

“These variable engraftment patterns have not been observed to date in data from the other nine Fabry disease patients previously dosed in the Phase 1 trial and under the prior protocol amendments in the FAB-GT trial, or in data from any patients in our other ongoing clinical trials,” MacKay added.

According to Avrobio, this is evidence of a heterogeneous response and failure by some patients to trigger a durable production of functional AGA protein following the engraftment.

“In addition, the last 12 months have presented multiple challenging market and regulatory dynamics for our Fabry disease program, which would now be exacerbated by a meaningfully extended development timeline,” MacKay said.

Avrobio will cease enrollment for the FAB-GT Phase 2 trial but will continue monitoring patients enrolled for a total of 15 years, as required by regulators.

Patients who completed FAB-GT had the choice to enter an extension study (NCT04999059) to assess the therapy’s long-term safety and effects for up to 15 years.