Avrobio shares plummet as Fabry program axed, new trial starts slated for 2023

Avrobio already trimmed expectations for its Fabry disease gene therapy in May because of Sanofi's Fabrazyme approval, and now the biotech is axing it altogether.

Enrollment in a phase 2 trial of AVR-RD-01 has been halted after new data found that five patients may be resistant to engraftment, or when new blood-forming cells begin growing to make healthy blood stem cells, the company said Tuesday. Previously, Avrobio had found durable engraftment in 13 patients across three clinical programs. The new data means the development of the gene therapy would be "meaningfully extended," CEO Geoff MacKay said. 

The executive also blamed challenges to the "market and regulatory environment" for the rare disorder as reasons for shutting down the program. 

Avrobio had planned to run a registrational trial in mid-2022 comparing the gene therapy to Fabrazyme, which gained full FDA approval last year after 18 years in the accelerated approval stage. Avrobio also wanted to take the accelerated pathway, but Fabrazyme's full approval altered those plans. 

RELATED: Avrobio plans head-to-head Fabrazyme trial after FDA changes path to market

“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," MacKay said.

Now, Avrobio will focus on a pipeline of other gene therapies to extend its cash runway into the first months of 2024. The company's stock slid 35% to $2.64 apiece as of 10:46 a.m. ET. 

With the shifted priorities, Avrobio will have a busy 2022 gearing up for multiple planned trial starts in 2023. The Cambridge, Massachusetts biotech will give an update on a phase 1/2 trial of AVR-RD-04 next month at the lysosomal diseases conference WORLDSymposium 2022. That gene therapy is being investigated for cystinosis, a rare disease characterized by an abnormal buildup of the amino acid cystine. Avrobio expects to speak with regulators about a mid-stage study. 

The biotech will also provide a clinical update in the next few months on its Gaucher disease type 1 therapy, AVR-RD-02, which is in a phase 1/2 trial in the U.S., Canada and Australia. Gaucher is an inherited disorder characterized by a missing enzyme that helps tear apart the fatty substance lipids, which leads to build-up in organs like the spleen and liver. 

Further down the line, Avrobio plans to ask regulators about a phase 2/3 clinical strategy for its gene therapy in Gaucher disease type 3, with could kick off in 2023. 

The biotech aims to begin two other trials that year: a phase 1/2 study of AVR-RD-05 for Hunter syndrome and an early-stage test of AVR-RD-03 in Pompe disease.