Avrobio gene therapy eliminates toxic substrate in Fabry patient

The first Fabry disease patient treated with Avrobio’s plato gene therapy platform in a phase 2 trial has experienced the complete clearance of toxic kidney substrate. 

Avrobio designed the plato platform to optimize vector copy number, personalize the conditioning regimen, facilitate automated manufacturing and otherwise improve and industrialize its lentiviral vector-based approach to the treatment of genetic diseases. Late in 2019, a Fabry patient in a phase 2 clinical trial of ex vivo lentiviral gene therapy AVR-RD-01 became the first patient dosed using plato. 

Having tracked the patient for 12 months, Avrobio shared details of the efficacy of plato on Monday. The patient experienced a 100% reduction in Gb3 inclusions at 12 months. At baseline, the patient averaged four Gb3 inclusions per peritubular capillary. One year later, the figure had fallen to zero. The results were generated by two blinded pathologists who independently assessed 99 kidney biopsy images.

The finding, while coming from just one patient, offers encouragement for Avrobio’s prospects in Fabry, particularly in light of the 87% reduction in Gb3 seen in the other participant with an evaluable kidney biopsy. Gb3 is a fatty substrate linked to organ damage in Fabry patients. Change in Gb3 inclusions is the primary efficacy endpoint of the 12-subject clinical trial. 

In draft guidance, the FDA called Gb3, also known as GL-3, “a surrogate endpoint reasonably likely to predict clinical benefit to support accelerated approval.” Amicus Therapeutics assessed the effect of Galafold on Gb3 in one of the phase 3 clinical trials that supported its FDA approval. The biomarker also supported the approval of Sanofi’s Fabrazyme.
Avrobio shared details of the kidney biopsy findings alongside other clinical trial updates. In the wider Fabry program, Avrobio reported “generally stable and sustained” changes in biomarkers in the nine patients treated so far. Avrobio was yet to see an unexpected safety event as of the cutoff. 

The biotech also released an early look at responses in a phase 1/2 trial of AVR-RD-02 in patients with Gaucher disease type 1. Avrobio said the first patient remains off enzyme replacement therapy and has experienced a “substantial improvement” in biomarkers six months after treatment.

Shares in Avrobio rose 20% in premarket trading.