- Avrobio, a Cambridge, Massachusetts-based gene therapy developer, will unexpectedly stop work on one of its most advanced treatments, citing disappointing results from a clinical trial that contrast with earlier, more promising findings.
- In a statement Tuesday, Avrobio said it would stop recruiting patients into a mid-stage study testing its gene therapy for Fabry disease, a rare inherited disorder, and deprioritize the research program. Monitoring will continue for the 14 Fabry patients who have received Avrobio's therapy so far.
- Avrobio made its decision after data from three of the five most recently treated patients showed declining levels of the critical protein the company's treatment is meant to produce. Other results indicated the therapy, which consists of genetically modified stem cells, was not taking root in the body as anticipated, suggesting possible resistance to treatment, according to Avrobio.
Fabry is one of several dozen diseases known collectively as lysosomal storage disorders, all caused by genetic breakdowns in how the body's cells process complex fats or sugars. Treatment, when it's available, usually involves infusions of the digestive proteins that people with these illnesses are missing.
More recently, several lysosomal storage disorders, among them Fabry, have become the target of a cluster of biotech companies that aim to address the genetic cause of these conditions more directly.
In Avrobio's case, the company uses a type of virus known as a lentivirus to genetically modify a patient's own stem cells. The hope is this approach will help patients express functional versions of the genes that encode for proteins missing in Fabry and other lysosomal storage disorders like Gaucher disease and cystinosis.
Early findings from a study of Avrobio's Fabry gene therapy in five men in Canada showed promise, and the biotech had advanced the treatment into a larger Phase 2 study. Several patients were able to stop taking standard treatment as a result of the therapy, which led to increases in levels of the target protein and, in one patient, complete clearance of the toxin that protein processes.
As late as early 2021, Avrobio was hopeful the accumulating data could position it to discuss with the Food and Drug Administration a path toward an accelerated OK for the therapy. But a decision by the agency in March to grant full approval to Fabrazyme, the standard enzyme replacement therapy used in Fabry, closed off that possibility and forced Avrobio to change its plans.
With a longer road toward a potential approval in the background, the disappointing data Avrobio disclosed Tuesday led the company to discontinue further development of the therapy and focus its resources on other research. Shares fell by more than a third Tuesday in response to the news.
"[T]he 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," said Avrobio CEO Geoff Mackay in a statement.
The new study results were "discordant" with prior findings, Mackay added. Specifically, they showed a less promising pattern of "engraftment," or the process by which modified stem cells take root in the body after being reinfused.
While previously treated patients had experienced durable engraftment out as far as 54 months, more recently treated participants in the Phase 2 study showed signs the treatment wasn't properly taking effect.
According to Avrobio, differences in how Fabry disease presents may result in "intrinsic resistance" to engraftment in some patients. The company also investigated factors related to the treatment procedure, which includes use of "conditioning" drugs that are meant to clear out space in the bone marrow for the modified cells.
Avrobio said the drug product used to treat the five patients met all quality criteria before being released for use in patients.
The company will now shift its focus to its gene therapies for Gaucher and cystinosis, both of which are in clinical testing. As a result of discontinuing its work in Fabry, Avrobio now expects the $200 million in cash it holds to last until early 2024.