AviadoBio’s AVB-101, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat frontotemporal dementia (FTD) associated with progranulin (GRN) gene mutations (FTD-GRN), has received both clearance of its investigational new drug (IND) application and fast track designation from the FDA.1
Under the IND, AviadoBio intends to expand clinical trial activities to the United States for its ongoing phase 1/2 ASPIRE-FTD clinical trial (NCT06064890), which was initiated in Europe in October 2023.1,2 The company expects that study activities will be initiated in the United States in 2024.
“The IND clearance and Fast Track designation of AVB-101 are important milestones for the FTD community and for our company,” Lisa Deschamps, MBA, the chief executive officer of AviadoBio, said in a statement.1 “Sadly, there are currently no disease-modifying therapies approved for the treatment of people living with frontotemporal dementia with progranulin mutations. Receiving fast track designation underscores the significant need for treatment options for these patients, and we are eager to soon open US clinical trial sites and offer an innovative option for eligible patients with FTD-GRN.”
The open-label, multicenter, ascending dose trial is expected to treat approximately 9 patients in total across 2 dose cohorts.2 AviadoBio noted that patients will receive the gene therapy via a 1-time administration to the thalamus by way of a minimally invasive stereotactic neurosurgical procedure, an approach that is expected to allow for a lower dose of AVB-101 and to limit the potential for systemic exposure. The study is currently recruiting patients aged 30 to 75 years at centers in multiple cities in both Poland and Spain.
- AviadoBio's AVB-101, a gene therapy for frontotemporal dementia (FTD) associated with progranulin gene mutations, has received FDA clearance for its investigational new drug (IND) application and fast track designation.
- The phase 1/2 ASPIRE-FTD clinical trial, initiated in Europe, is set to expand to the United States in 2024, focusing on treating FTD patients with AVB-101 via a minimally invasive stereotactic neurosurgical procedure.
- AVB-101 utilizes adeno-associated virus (AAV) technology and showed promising preclinical results in nonhuman primates.
Recently, AviadoBio presented new preclinical data supporting clinical trial initiation at the 30th Annual Congress of the European Society of Gene & Cell Therapy (ESGCT), held October 24-27 in Brussels, Belgium.3 The data demonstrated that all evaluated doses of intrathalamic delivery of AVB-101 were well-tolerated in nonhuman primates with no mortalities or observable clinical adverse events reported. Human progranulin (PRGN) was most abundant in the thalamus and detected throughout the brain, including in the temporal and frontal lobes, which are severely affected by FTD-GRN. Furthermore, a dose-dependent increase in PRGN levels was seen in the cerebrospinal fluid. It was also noted that in most visceral tissues vector genomes were minimal or undetectable. These findings built on preclinical data previously reported at the 25th American Society for Gene & Cell Therapy (ASGCT) Annual Meeting, held in Washington, DC, May 16 to 19, 2022, that showed a decrease in disease pathology in a PRGN-deficient mouse model that received AVB-101 via intrathalamic injection.
AVB-101, which utilizes an AAV9 vector, is expected to provide a functional copy of GRN along with additional genetic material included with the intent of enabling the gene’s activity in the neurons.2 In April 2022, AVB-101 was granted orphan drug designation by both the FDA and the European Commission.4
“We are using AAV technology and taking a novel approach to deliver a functional copy of the GRN gene directly to the brain via bilateral, MRI-guided intrathalamic infusion with the aim to restore normal levels of the progranulin protein,” David Cooper, MD, the chief medical officer of AviadoBio, added to the statement.1 “Our preclinical program shows robust biodistribution to the brain areas where it is needed to restore levels of progranulin, potentially slowing or stopping the progression of FTD-GRN, with little to no progranulin in the rest of the body where it may have adverse effects.”
1. AviadoBio announces FDA IND clearance and fast track designation for AVB-101 for the treatment of frontotemporal dementia with progranulin (GRN) mutations. News release. AviadoBio. November 6, 2023. Accessed November 10, 2023. https://aviadobio.com/en/aviadobio-announces-fda-ind-clearance-and-fast-track-designation-for-avb-101-for-the-treatment-of-frontotemporal-dementia-with-progranulin-grn-mutations/
2.AviadoBio announces initiation of phase 1/2 clinical trial, ASPIRE-FTD, evaluating AVB-101 in people with frontotemporal dementia with GRN mutations. News release. October 10, 2023. Accessed October 10, 2023.https://aviadobio.com/en/aviadobio-announces-initiation-of-phase-1-2-clinical-trial-aspire-ftd/
3. AviadoBio announces initiation of phase 1/2 clinical trial, ASPIRE-FTD, evaluating AVB-101 in people with frontotemporal dementia with GRN mutations. News release. October 10, 2023. Accessed October 10, 2023.https://aviadobio.com/en/aviadobio-announces-initiation-of-phase-1-2-clinical-trial-aspire-ftd/
4. AviadoBio’s Gene Therapy Candidate Receives Orphan Designation from Food and Drug Administration and European Commission in Frontotemporal Dementia. News release. AviadoBio. April 27, 2022. Accessed October 10, 2023.https://aviadobio.com/aviadobios-gene-therapy-candidate-receives-orphan-designation/