Gene therapy developer Avrobio is expected to start a key study this year to test its experimental treatment for rare metabolic disorders.Instead, the company shelved the treatment candidate after reviewing new clinical data Exhibit variability Among patients who have recently received treatment-enough to extend the development timeline of a plan that has had to adapt to unexpected regulatory and competitive challenges in the past year.
Experimental gene therapy AVR-RD-01 is a potential treatment Fabry disease, A lysosomal storage disease, stems from a genetic defect in a key enzyme called α-galactosidase A. Without it, cells cannot break down a type of fat, which in turn will accumulate and cause organ dysfunction. Although enzyme replacement therapy can be used to infuse patients with the synthetic enzymes needed by Fabry patients, Avrobio, headquartered in Cambridge, Massachusetts, aims to solve the disease by addressing underlying genetic problems.
AVR-RD-01 is a lentiviral gene therapy that harvests stem cells from patients, uses lentivirus to deliver functional copies of genes to these cells, and then injects the modified cells back into the patient. What follows is called implantation: The engineered cells are taken up by the bone marrow, where they multiply and produce a sufficient number of new cells with functional genes. To date, an open-label Phase 2 study has recruited 9 patients. Avrobio said on Tuesday that the five most recently administered patients in the clinical trial all had different implant patterns.
Avrobio has two other clinical phase projects. According to the company, implantation variability was not observed in these clinical trials, nor was implantation variability observed in patients in the phase 1 trial of Fabry disease. Although no safety issues have been reported for patients with Fabry disease, Avrobio stated that it will stop participating in the study, but will continue to monitor patients who have previously administered drugs in the next 15 years, which is a requirement of the regulatory agency.
“We are fully aware of the impact of this difficult decision on the patients and families we have been fortunate to have met over the years, but we believe that prioritizing and stopping our registration for the Fabry disease program is the right step. Avrobio has retained us to continue The ability to develop therapies has the potential to address urgent unmet needs in the lysosomal disease community,” Avrobio CEO Geoff MacKay said in a prepared statement.
The surprising implant variability is the latest setback in Avrobio’s plan to quickly review it at the FDA. These plans changed in March last year when the FDA fully approved Fabrazyme, an enzyme replacement therapy that has been available under accelerated approval for the past 18 years. The full approval of Sanofi products limits Avrobio’s ability to also use accelerated approval pathways, unless biotechnology can show clinical benefits beyond what Fabrazyme provides. On the contrary, Avrobio said last year that it would use the same clinical trial targets to seek full FDA approval, which is the basis for Fabrazyme’s full approval. The strategic shift means that Avrobio needs to modify its clinical trial design. Until Tuesday, the plan for the study was to begin in the middle of this year.
Looking to the future, Avrobio said it plans to focus on two other clinical phases of lysosomal storage disease projects: Gaucher disease type 1 and cystinopathy. Both are in phase 1/2 testing; the Gaucher plan is expected to release an update in the first half of this year, and the cystinopathy plan is expected to report the update at the annual lysosomal disease conference WORLDSymposium scheduled for February this year.
in a Investor introduction, Avrobio said it plans to discuss with regulators later this year a plan to advance the cystinopathy program to phase 2 testing. Avrobio’s preclinical programs are used for Gaucher disease type 3, Hunter syndrome and Pompe disease.
As the pipeline re-prioritized, Avrobio stated that it should have sufficient funds to support the company for the next two years. As of the end of the third quarter of 2021, the biotech company reported a cash position of US$201 million.
picture: Lex, Getty Images
