Zolgensma for dementia? AviadoBio gains orphan tag for one-dose gene therapy

Move over, Zolgensma. A new one-dose therapy that could provide a similar mode of treatment for the red-hot therapy area of neurodegenerative disorders has received orphan designation from regulators on both sides of the Atlantic.

AviadoBio’s preclinical drug, AVB-101, is an adeno-associated virus (AAV) gene therapy designed for patients with frontotemporal dementia (FTD) that have mutations of the progranulin gene. FTD is a debilitating form of early-onset dementia that currently has no approved therapies, and the drug has received orphan designation from both the FDA and the European Commission, the company announced today.

Following an $80 million funding round in December 2021 led by New Enterprise Associates and including the likes of Johnson & Johnson’s investment arm JJDC, the London-based biotech is aiming to enter clinical trials in the U.K. by the end of the year before expanding to other countries in 2023.

Recent advances in Alzheimer’s disease developments from the likes of Biogen have led to a resurgence in interest in the central nervous system space, which had at one point been widely perceived to be too complex to tackle, Lisa Deschamps, CEO of AviadoBio, told Fierce Biotech.

“There’s been a tremendous amount of interest from investors,” Deschamps said. “We’ve had great initial discussions with regulators, both in the U.S. and the U.K.”

Lisa Deschamps
Lisa Deschamps (AviadoBio)

Based on research from King’s College London and the UK Dementia Research Institute, AVB-101 is designed to slow or arrest disease progression by delivering a functional copy of the GRN gene throughout the central nervous system to restore normal levels of the progranulin protein.

FTD is the second most common form of dementia in under-65s after Alzheimer’s, affecting between 50,000 and 60,000 patients in the U.S. and more than 100,000 in the EU. Of these cases, between 30% and 40% are linked to mutations in three genes including GRN.

“One of the challenges in neurodegenerative conditions and neurological conditions overall is crossing the blood-brain barrier,” Deschamps said. “Many companies have tried, and the biggest challenge is to do it at safe levels without toxicity. So having a very targeted approach will allow us to strive to achieve that for patients.”

Applying lessons from Zolgensma 

The comparisons with Zolgensma, Novartis' spinal muscular atrophy therapy, don’t end with AVB-101’s status as a one-dose gene therapy for a hard-to-treat condition. In her previous role as chief business officer at Novartis Gene Therapies, Deschamps oversaw the commercialization of the drug and has brought that expertise to AviadoBio.

“A one-time therapy just goes against every conventional norm that exists. Our systems and infrastructure are not yet at the same juncture as the scientific breakthrough,” the CEO said. “[My] experience … highlights the importance of how much collaboratively you need to do across all stakeholders, from the regulators to the policymakers to the patient advocacy groups [and] the clinicians. It really takes a full holistic approach as you’re working through these gene therapy programs.”

Zolgensma’s status as the world’s most expensive drug attracted a lot of attention, not all of it positive. Pricing is still a long way off for AVB-101, but Deschamps hopes that, over time, cost will become less of an issue for this cutting-edge class of therapies.

“You have to assume that early on you’re going to have very small populations, very inefficient manufacturing, very high cost of goods, and you have to focus on the disease areas you’re going in[to],” the CEO said. “My hope is that as gene therapy development, manufacturing [and] our learnings evolve and mature, we’ll be able to bring therapies in at very different levels.”

While AviadoBio is focused on bringing AVB-101 to the clinic, the company has a broader program looking at another degenerative nervous system disease called amyotrophic lateral sclerosis, and it has yet to disclose its full pipeline.

“So more to come—stay tuned,” Deschamps says.