Drug Development, Gene Therapy, Results

Avrobio shares blasted after trial update sours outlook on gene therapy for Fabry disease

Avrobio made the leap onto Nasdaq a few months ago and then proceeded to run the table largely on a snapshot of efficacy for its lead gene therapy to treat Fabry disease. On Monday, though, an updated look at a key data point sent investors running, collapsing the share price.

By the end of the day on Monday Avrobio’s stock $AVRO had been beaten down 52%, wiping out hundreds of millions of dollars in market cap.

Geoff MacKay

On the surface, Avrobio’s press release indicated nothing less than continued success with AVR-RD-01, with CEO Geoff MacKay saying he was “encouraged” by the therapeutic effect researchers were seeing in several patients. Their lentiviral treatment appeared to be doing the job it was designed to do — inserting healthy copies of the GLA gene that encodes for a deficient enzyme in Fabry disease and seeing a rise in enzyme activity.

But the slide show for the day also included a disturbing sight, with the vector copy numbers in peripheral blood dropping in 4 out of 4 cases over a span of anywhere from 1 to 18 months. 

The VCN is a key marker for the transfer of healthy genes into cells. And as anyone who follows bluebird bio can tell you, if the VCN isn’t right, then nobody’s happy. Bluebird went back to the drawing board after tracking VCN numbers of 0.3 and 0.6 in the first generation of its gene therapy for beta-thalassemia, heralding a spike to 1.5 and 2.1 for two patients in a Lenti-Globin study. And bluebird knows full well that a higher, or rising, VCN breeds confidence.

So what spooked investors Monday? Here are the details:

Patient #1 started therapy with a VCN of 0.7 and then researchers tracked a steady drop to 0.1 18 months post-treatment. Patient #2 dropped from 1.4 to 0.4 in 6 months. Patient #3: 0.8 to 02 in 1 month. And patient #4 went from 0.7 to 0.5 in a few months.

In gene therapy, companies are pushing to create new once-and-done treatments. Any indication that their product can’t stand up over time plays havoc with the business model. So investors bailed on the stock.

Avrobio still has plenty of opportunities to do better. But next time you can expect a lot of people to move straight to the VCN as the company talks about therapeutic effects.


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Biotech Investment Analyst
SV Health Investors Boston, MA
Research Scientist - Disease Biology
Recursion Pharmaceuticals Salt Lake City, UT
Senior Scientist - Predictive Pharmacology
Recursion Pharmaceuticals Salt Lake City, UT
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Cadent Therapeutics Cambridge, MA
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twoXAR Mountain View, CA

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