Gene Therapy, Results

Avrobio takes a second stab at a good first impression — but durability questions still dog gene therapy

Geoff MacKay

Four months ago, Avrobio’s shares $AVRO were subjected to a ritual slaughter on Wall Street after investors were spooked by their lead gene therapy’s poor performance on a key measure reflecting potential durability. Today, the top execs at the company are making a new pitch, hoping that they can win over the market with updated evidence that the gene therapy is working for patients with Fabry disease.

But you can expect plenty of more questions to come on its longterm prospects.

The big question last October was centered on the vector copy numbers reflected in the handful of patients who had received Avrobio’s AVR-RD-01. The VCN is a marker for the gene therapy’s ability to insert healthy copies of the GLA gene that encodes for a deficient enzyme in Fabry disease. And it has to be right in a field pursuing once-and-done treatments. 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.

In Avrobio’s case, the VCN headed down in several cases. And their release underscores that adding a few months of observation didn’t improve matters.  

According to CEO Geoff MacKay, who decided to add the VCN numbers to this morning’s release instead of waiting for the evening presentation of the data for analysts, this was all “as expected.” Patient #1’s VCN, he said in an email, is “stable” at 0.1.

In the October results we saw:

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: 0.2 to 0.8 at 3 months. And patient #4 went from 0.7 to 0.5 in a few months.

In the update today Patient #1’s VCN is still at 0.1 22 months after treatment. Patient #2 is still at 0.4 at 12 months and Patient #3 dropped to 0.5 at 6 months. Patient #1 in the Phase II is at 0.2 at 6 months, dropping from 0.5 at 3 months after starting out at 0.2.

The biotech set out to highlight the biomarker evidence to back up their therapy’s ability to substitute the chronic use of enzyme replacement therapy for Fabry. The company noted:

All (evaluable) patients with reported data exhibit AGA enzyme activity above the diagnostic range for males with classic Fabry disease after receiving AVR-RD-01, including at 22 months for Patient 1 of the Phase 1 study.

Two of the patients in the Phase I have suspended use of ERT.

We’ll see how investors think about that now. But you can expect plenty of questions ahead on moves the company is making to improve the VCN rankings.

As of yesterday’s close AvroBio’s shares were down 70% from their high of $51 last fall. The stock was treading water at the open this morning, slightly in the red during mid-morning trading.


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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

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