- Gene therapy developer Avrobio no longer plans to seek an accelerated approval for its experimental Fabry disease treatment in the U.S. after a recent Food and Drug Administration decision to grant full clearance to the standard drug used for decades to treat the rare metabolic disorder.
- In March, the FDA converted an accelerated approval it gave to Sanofi's Fabrazyme in 2003, adding to the drug's labeling additional study results on long-term treatment as well as data from real-world use. As a result, Avrobio can't request a conditional OK for its therapy from the FDA, forcing a change of plans that will push back approval discussions until after the biotech company runs a larger clinical trial.
- Avrobio plans to start that trial mid-next year, proposing a study that would test its gene therapy head to head against Fabrazyme. The company is currently running a mid-stage study of its therapy in the U.S., Canada and Australia and plans to expand it to include as many as 14 Fabry patients.
For much of the past two decades, Fabrazyme was the only treatment available in the U.S. for patients with Fabry, one of dozens of diseases caused by a breakdown in cellular metabolism. Fabrazyme works by replacing an enzyme that's missing in Fabry patients and is responsible for breaking down a toxic waste build-up in cells.
Until March, when the FDA confirmed a full approval, Fabrazyme's authorization was still considered conditional, based on the drug's ability to reduce levels of the relevant toxin in the kidney.
The FDA's decision, according to Avrobio, closed off its ability to seek a quick clearance for its gene therapy. The agency requires accelerated approvals to address an "unmet medical need," which can include diseases for which there is already a marketed drug but only if a new treatment meets other criteria like providing a "meaningful advantage" over existing therapy.
Avrobio claims Fabrazyme's full approval will allow it to seek a similar nod for its therapy based on toxin reductions in the kidney. But the company will need to run a trial directly comparing the two treatments on that measure, rather than relying on an expanded version of the Phase 2 study it's already enrolling.
As a result, an approval for Avrobio's treatment could be meaningfully delayed, according to Mani Foroohar, an analyst at SVB Leerink. Foroohar now forecasts the gene therapy to be available by 2025, compared to a previous estimate of 2023. The timing for Avrobio will depend a good deal on the size and length of the study the FDA recommends the company conduct.
In a statement Monday, Avrobio CEO Geoff MacKay said the biotech plans to design a head-to-head trial with "a scope, size and duration comparable to other gene therapy trials."
Avrobio isn't the only company tripped up by Fabrazyme's full approval. Late last month, Protalix BioTherapeutics confirmed the FDA had rejected its experimental Fabry drug PRX-102 due to a manufacturing inspection agency officials couldn't conduct as a result of pandemic-related travel restrictions.
But Protalix said the agency also noted that any future resubmission of PRX-102 would require the company to address Fabrazyme's full approval.
Like Fabrazyme, Protalix is an enzyme replacement therapy. Avrobio's treatment, by comparison, aims to correct the genetic mutation that causes Fabry by modifying patient stem cells to produce the missing enzyme. It's one of a growing pipeline of gene therapies aimed at so-called lysosomal storage disorders
Early results showed the therapy can dramatically lower toxin levels in the kidneys, with a 100% reduction reported in one patient a year after treatment.
Avrobio intends to discuss its plans for the new study, as well as its manufacturing process, with the FDA. The company hopes to schedule a meeting on the latter point sometime in the second half of the year.
Shares in Avrobio fell by more than 10% in Monday morning trading following the news.