New Medicines

Fabry's disease in males aged>16 years who have not previously received treatment with enzyme replacement therapy (ERT) and/or chaperone therapy


New molecular entity

Development and Regulatory status

Jan 22AVROBIO announced it is deprioritising its Fabry disease program due to several factors, including new clinical data showing variable engraftment patterns from the five most recently dosed Phase 2 FAB-GT patients which would significantly extend the program’s development timeline, an increasingly challenging market and regulatory environment for Fabry disease. [8]
Nov 21ARVOBIO announces further trial(s) to begin in 2022.[6]
May 21Following the FDA removal of accelerated approval for Sanofi´s Fabrazyme, Avrobio are unable to seek accelerated approval of ACR-RD-01 based on its current PII data. Instead Avrobio now plan to run a new registration trial mid 2022 to compare AVR-RD-01 to Fabrazyme [5].
Nov 20ARVOBIO announces intention to submit its briefing book to the US FDA to obtain accelerated approval for AVR RD 01 in Fabry´s disease.[2]
Oct 20EMA grant Orphan Drug status for Fabry´s disease in EU. [2]
Dec 18US FDA granted orphan drug designation.[2]


Gene therapy to be given as a single, one-off dose. Autologous haematopoietic stem cells are collected, genetically modified ex vivo using a lentiviral vector containing the functional GLA gene. Cells are infused back into the patient. [2]
Anderson-Fabry disease is an X-linked recessive inborn error of glycosphingolipid metabolism caused by deficiency of alpha-galactosidase A. It is estimated to occur in 1 in 55,000 males in the classical form but the atypical variant may be more common [1].
Fabry's disease in males aged>16 years who have not previously received treatment with enzyme replacement therapy (ERT) and/or chaperone therapy
Intravenous infusion

Trial or other data

Jan 22AVROBIO report that PII would need to be extended for a much longer period after data from 13 pts demonstrated durable engraftment out of 9 to 54 months. However, findings from the latest 5 pts showed different results, including a reduction to near baseline levels in alpha-galactosidase A (AGA) enzyme activity in plasma and leukocytes, plus a drop in the vector copy number (VCN) in whole blood. Due to the large variations in results, AVROBIO will be forced to reassess its processes and other parameters, which could be costly. [8]
Nov 21PII (NCT03454893) trial is due to complete and should have finished collection of primary outcome data earlier in Jul 21 [7].
Aug 21A long-term follow-up study (NCT04999059) to assess the long-term safety and durability of AVR-RD-01 treatment in participants who received a single dose administration of lentiviral gene therapy in Study AVRO-RD-01-201(NCT03454893) is enrolling by invitation. Participants will continue periodic safety and efficacy assessments in this long-term follow-up study for approximately 14 years (Dec 2036) [7].
Feb 21Company announced a 100% reduction/complete clearance (p<0.0001) of toxic substrate in the kidney biopsy (which is the primary outcome measure) of the first patient dosed with the plato® gene therapy platform in the ongoing PII trial of AVR-RD-01. Interim data from 4 pts in the trial has previousely showed that the 1st pt produced an endogenous supply of functional AGA enzyme up to 22 months post-treatment. The 3rd and 4th patients dosed are also showing good signs of efficacy. AVR RD 01 has been generally well tolerated and no safety events related to AVR RD 01 reported. Four serious adverse events (relating to conditioning regimen with melphalan, stem cell mobilization, underlying disease or pre-existing conditions) were reported but were not attributed to AVR RD 01. The trial completes in Nov 2021. [2-4]
Feb 18PII open label, single arm trial in Australia, Canada and the US (NCT03454893) started to evaluate the efficacy and safety of AVR RD 01, in males aged >16 who have not previously received treatment with enzyme replacement therapy (ERT) or other therapies for Fabry disease. The primary efficacy endpoint is change from baseline in the average number of Gb3 inclusions per peritubular capillary (PTC)3 as measured in a kidney biopsy 1 year post-treatment. [2,3]