AviadoBio Begins Trial for Frontotemporal Dementia Gene Therapy AVB-101

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The open-label, multicenter, ascending dose trial is expected to treat approximately 9 patients in total across 2 dose cohorts.

AviadoBio has initiated the phase 1/2 ASPIRE-FTD clinical trial (NCT06064890), which is evaluating 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).1

The open-label, multicenter, ascending dose trial is expected to treat approximately 9 patients in total across 2 dose cohorts. 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. Participants in the trial will be treated at locations in the United States and Europe; according to the clinicaltrials.gov page, centers in Poland and Spain are currently recruiting patients. 

AviadoBio also plans to announce new data from the preclinical research for AVB-101 later this month at the 30th Annual European Society of Gene & Cell Therapy (ESGCT) meeting, held in Brussels, Belgium on October 24 to 27, 2023. The company noted that the data, which come from nonhuman primate research using intrathalamic delivery, showed widespread expression of progranulin protein in the brain; tolerability was also deemed good.

“FTD is a devastating form of early-onset dementia and there are currently no disease-modifying treatments available,” Lisa Deschamps, MBA, the chief executive officer of AviadoBio, said in a statement.1 “The initiation of our company’s first clinical trial demonstrates our commitment to developing and delivering potential transformative gene therapies for those living with neurodegenerative disorders such as FTD.”

AVB-101 utilizes an AAV9 vector and is intended to provide a functional copy of GRN along with other genetic material intended to enable the gene’s activity in the neurons. ASPIRE-FTD will seek to establish whether the treatment can stop or slow the progression of FTD-GRN, in addition to evaluating safety. The ability of AVB-101 to elevate progranulin protein to normal or above normal levels in the brain will also be assessed. The study is open to patients aged 30 to 75 years.

“While it is known that progranulin protein supplementation is possible using gene therapy, effective brain distribution remains challenging primarily because of the brain’s anatomy,” David Cooper, MD, the chief medical officer of AviadoBio, added to the statement.1 “Our aim is to use intrathalamic delivery to facilitate biodistribution of the PGRN protein to the areas of the cortex impacted by FTD. AVB-101 has already shown great promise in preclinical studies, and we now look forward to this important next step in its clinical development.”

AVB-101 was granted orphan drug designation by both the FDA and the European Commission in April 2022.2 At that time, AviadoBio announced that it was expecting to initiate the clinical trial for the gene therapy before the end of 2022.

The company previously reported data from preclinical research on AVB-101 at the 25th American Society for Gene & Cell Therapy (ASGCT) Annual Meeting, held in Washington DC on May 16 to 19, 2022.3 Among the finds were reductions in disease pathology observed in a progranulin-deficient mouse model that was treated with AVB-101 via intrathalamic injection.

“The data from these studies are highly compelling and give us great confidence in the potential of precision micro-dosing of AVB-101 to effectively treat FTD by delivering a functional copy of the GRN gene to the right areas of the central nervous system to impact disease progression while minimizing off-target expression and distribution,” Chris Shaw, MD, MBBS, the cofounder and chief scientific and clinical advisor of AviadoBio, said in a May 2022 statement.1 “The findings from the biodistribution studies are particularly exciting, demonstrating that effective and targeted distribution of a gene therapy is possible via intrathalamic injection. We look forward to continuing our clinical studies as we move ever closer to addressing the unmet need in FTD.”

REFERENCES
1. 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/
2.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/
3. AviadoBio presents preclinical data at ASGCT 2022 demonstrating that AVB-101 represents a novel and promising approach to treatment of frontotemporal dementia. News release. May 17, 2022. Accessed October 10, 2023. https://aviadobio.com/en/aviadobio-presents-preclinical-data-at-asgct-2022/

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