Breaking News

Avrobio announced new clinical data from its investigational programs for Fabry disease and cystinosis. The data will be presented at the American Society of Gene & Cell Therapy, or ASGCT. Four patients have been dosed in the Phase 2 trial of AVR-RD-01, Avrobio's investigational lentiviral gene therapy for Fabry disease. The first patient continued to show increased leukocyte and plasma AGA enzyme activity, now up to 22 months post-treatment. These data suggest the patient is producing an endogenous supply of functional alpha-galactosidase, or AGA, enzyme, which is essential to prevent the accumulation of a toxic metabolite, lyso-Gb3, in tissues including the heart and kidneys. A sustained decrease in plasma lyso-Gb3 and total Gb3 levels has previously been reported for this patient out to 18 months. The third patient had a sustained decrease in plasma lyso-Gb3 and total Gb3 levels nine months after dosing. This patient also had a stable vector copy number, or VCN, out approximately one year post-treatment, suggesting successful engraftment. The fourth patient, who is also the first to be dosed with Avrobio's plato gene therapy platform, had a 43% reduction in the toxic metabolite plasma lyso-Gb3 at one month. At three months, he also had leukocyte enzyme and plasma enzyme activity levels approximately three times higher than the mean activity level of the first three patients in the same trial at the same timepoint. While the presentation will focus on data updates for its Phase 2 trial, the company also reports that all three Phase 1 patients who discontinued enzyme replacement therapy, or ERT, after receiving AVR-RD-01 gene therapy, remain off ERT as of April 27. As of the safety data cut-off date of November 26, 2019, there have been no safety events attributed to AVR-RD-01 drug product in either the Phase 1 or Phase 2 trial. Through the safety data cut-off date, four serious adverse events, or SAEs, have been reported in the FAB-201 trial and two SAEs in the Phase 1 trial. The fourth Phase 2 patient, who was dosed after the safety data cut-off date, has reported an SAE, which was not attributed to AVR-RD-01 and which subsequently resolved. Across both studies, each of the SAEs has been consistent with the conditioning regimen, stem cell mobilization, underlying disease or pre-existing conditions. Pre-existing low anti-AGA antibody titers have been detected in four patients in the Phase 1 trial and a transient low titer was observed but not detectable in subsequent measures in one patient in the Phase 2 trial. Avrobio continues to actively identify participants for the Phase 2 Fabry disease trial in Australia, Canada and the U.S. The FAB-201 trial is an ongoing open-label, single-arm Phase 2 clinical trial evaluating the efficacy and safety of AVR-RD-01 in eight to 12 treatment-naive Fabry disease patients. New data will also be presented from the first patient dosed in the investigator-sponsored Phase 1/2 trial of AVR-RD-04 for cystinosis, a progressive disease marked by the accumulation of cystine in cellular organelles known as lysosomes. This buildup can cause debilitating symptoms including kidney failure, corneal damage and thyroid dysfunction, often leading to a shortened lifespan. Currently, more than 90% of treated cystinosis patients require a kidney transplant in the second or third decade of life. The current standard of care for cystinosis is cysteamine, a burdensome treatment regimen that can require dozens of pills per day and may not prevent overall progression of the disease. Six months following administration of AVR-RD-04, the patient's estimated glomerular filtration rate, which is a measure of kidney function, improved from 38 mL/mi/1.73m2 at baseline to 52 mL/mi/1.73m2. The patient's serum creatinine, another measure of kidney function, also improved, falling from 2.2 mg/dL at baseline to 1.6 mg/dL at six months. The patient stopped cysteamine treatment before administration of AVR-RD-04 and remains off cysteamine. As of the safety data cut-off date of January 27, which was approximately three months following administration of the investigational gene therapy to the first patient in the AVR-RD-04 program, there have been no reports of safety events attributed to the investigational drug product. In addition, no SAEs have been reported as of the safety data cut-off date. Adverse events did not suggest any unexpected safety signals or trends.