Gene therapy developer Avrobio was about to embark on a core study this year testing its experimental treatment for a rare metabolic disorder. Instead, the company puts the therapeutic candidate on the shelf after a look at new clinical data showed variability in newly treated patients – enough to extend the development timeline of a program that has already had to adapt to unexpected regulatory and competitive challenges in the past year.
The experimental gene therapy, AVR-RD-01, is a potential treatment for Fabry’s disease, a lysosomal storage disorder that results from an inherited deficiency of a key enzyme called alpha-galactosidase A. Without it, the cells are unable to break down a type of fat. , which in turn builds up and leads to organ dysfunction. While enzyme replacement therapy can be used to infuse patients with synthetic versions of the enzyme Fabry patients need, Cambridge, Massachusetts-based Avrobio, aimed to solve the disorder by solving the underlying genetic problem.
AVR-RD-01 is a lentiviral gene therapy produced by harvesting a patient’s stem cells, using a lentivirus to deliver a working copy of a gene to those cells, and then infusing the modified cells back into the patient. The following is called engraftment: the manipulated cells are taken up by the bone marrow, where they multiply and produce a sufficient number of new cells with the functional gene. An open-label phase 2 study has so far included nine patients. Avrobio said Tuesday that the five most recently dosed patients in the clinical trial had varying engraftment patterns.
Avrobio has two other programs in the clinical phase. Engraftment variability has not been observed in these clinical trials, nor has it been observed in patients in the Phase 1 test for Fabry’s disease, according to the company. Although no safety concerns have been reported in any of Fabry’s disease patients, Avrobio said it would stop admission in this study but continue to monitor the previously dosed patients for the next 15 years as required by regulators.
“We are fully aware of the impact this difficult decision has on the patients and families we have had the privilege of getting to know over the years, but we believe that downgrading and stopping enrollment in our Fabry disease program is the right thing to do. steps forward for Avrobio and retains our ability to continue to develop therapies with the potential to meet urgently unmet needs in lysosomal disorders, ”said Avrobio CEO Geoff MacKay in a prepared statement.
The surprising engraftment variability is the latest setback for a program that Avrobio had hoped would get a quick review by the FDA. These plans changed in March last year when the FDA gave full approval to Fabrazyme, an enzyme replacement therapy that has been available under accelerated approval for the past 18 years. Full approval of this Sanofi product limited Avrobio’s ability to also use the accelerated approval path, unless biotechnology could demonstrate a clinical benefit beyond what Fabrazyme offers. Instead, Avrobio said last year that it would seek full FDA approval using the same clinical trial target that was the basis for Fabrazymes’ full approval. The change in strategy meant that Avrobio had to revise its clinical trial design. Until Tuesday, the plan was for that study to begin in the middle of this year.
Going forward, Avrobio said it plans to focus on its two other lysosomal storage disorders in clinical stages: Gaucher’s type 1 disease and cystinosis. Both are in phase 1/2 test; The Gaucher program is expected to publish an update in the first half of this year, while the cystinosis program is expected to report an update at the WORLDSymposium, an annual lysosomal disease conference scheduled for February this year.
In an investor presentation, Avrobio said it plans to discuss with regulators later this year plans to promote the cystinosis program for Phase 2 testing. Avrobio’s preclinical programs are for Gaucher disease type 3, Hunter’s syndrome and Pompe’s disease.
With the pipeline reprioritization, Avrobio said it should have enough money to support the company for the next two years. At the end of the third quarter of 2021, biotechnology reported a liquidity of $ 201 million.
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