Avrobio Pauses Patient Dosing in AVR-RD-01 Gene Therapy Trials Due to COVID-19

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by Vanessa Pataia |

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Fabry trials, AVR-RD-01

In response to the COVID-19 pandemic, Avrobio has temporarily paused enrollment and dosing of new patients in Phase 1 and 2 trials testing its investigational gene therapy AVR-RD-01 for the treatment of Fabry disease.

However, identification of eligible patients will continue in Canada, Australia, and the U.S.

“As the global healthcare community responds to the increase in COVID-19 cases, many hospitals, including our clinical sites, have temporarily paused elective medical procedures, which includes dosing of new patients in clinical trials of our investigative gene therapies,” Geoff MacKay, Avrobio’s president and CEO, said in a press release.

Patient enrollment and dosing are expected to resume as hospitals allow. Data collection from dosed patients in the two AVR-RD-01 trials will continue, although the timing of data collection may be affected by the duration of interruptions related to the COVID-19 pandemic.

Fabry disease is caused by a defect in the GLA gene, which leads to a deficiency in the enzyme alpha-galactosidase A (AGA). This enzyme is essential for the breakdown of a fatty substance called globotriosylceramide (Gb3), which accumulates in cells, leading to cell and tissue damage.

AVR-RD-01 is a cell-based therapy that uses a patient’s modified hematopoietic stem cells — which generate other blood and immune cells — to produce a functional AGA enzyme.

Researchers use an engineered, harmless viral vector to carry a functional version of the GLA gene and introduce it into a patient’s stem cells before these cells are reinserted back into the patient.

Avrobio is conducting two clinical trials testing AVR-RD-01 in Fabry patients: a Phase 1 investigator-sponsored trial called FACTs (NCT02800070) and a Phase 2 trial called FAB-201 (NCT03454893).

Updated data from both trials was recently presented during the 16th Annual WORLDSymposium, which took place in February in Florida.

In the FACTs trial, Avrobio is assessing the safety and efficacy of AVR-RD-01 in male patients who have been treated with standard-of-care enzyme replacement therapy (ERT) for Fabry disease, for at least six months prior to receiving AVR-RD-01 therapy.

So far, five patients have been dosed in the FACTs trial, and four of these had reductions in blood levels of lyso-Gb3, a Fabry disease biomarker, ranging between 26% and 47% compared to the levels measured while on enzyme replacement therapy.

Three patients have discontinued enzyme replacement therapy and all remain off ERT at six, 14, and 15 months after dosing.

In the FAB-201 trial, AVR-RD-01’s safety and efficacy is being evaluated in male patients who had never received treatment for Fabry disease.

Four patients have already been dosed, and three showed sustained production of the AGA enzyme at nine, 12, and 18 months post-dosing. Two of the three patients also showed reduced blood levels of lyso-Gb3 levels, below their initial values, at six and 18 months following dosing.

The third patient, who has a non-classic variant of Fabry, had very low levels of lyso-Gb3 to start with and as such did not show a substantial decrease in plasma lyso-Gb3 levels.

Cardiac and kidney function measures remained within the normal range for patients who had available data at one year post-treatment.

Importantly, data from eight participants across the two trials, who have reached between six to 32 months post-treatment, show that the vector copy number — the average number of functional gene copies integrated into the cell DNA through the lentivirus vector — remained stable in these patients, which supports long-term engraftment.

As of Nov. 26, 2019, there were no safety events linked to AVR-RD-01 in either trial. Two serious adverse events in the Phase 1 trial and four in the Phase 2 trial were related to Fabry disease itself, pre-existing conditions, the steps involved in collecting the stem cells, or the conditioning regimen. No unexpected safety signals or trends were seen.

Despite the temporary pause in enrollment and dosing, patient identification for the FAB-201 trial will continue in Australia, Canada, and the U.S. More details on trial locations and contacts can be found here.

“We continue to support patient identification efforts across our clinical trials in Canada, Australia and the United States,” MacKay said. “While we’re fully committed to moving our clinical programs forward, Avrobio supports this temporary reallocation of resources to ensure hospitals can focus on meeting the needs of patients with COVID-19.”

Avrobio says its research activities remain on track, and expects to provide an update on the impact of the COVID-19 pandemic on its operations in May 2020.

“We are closely monitoring this rapidly evolving situation and the potential impact on our clinical trial programs,” MacKay said.