Experts Call for Better Trial Design, Alzheimer Disease Vaccine Shows Safety, FDA Accepts IND for LION-101

This week Neurology News Network covered a recently published paper calling for better design of early Alzheimer disease (AD) and frontotemportal dementia trials, the phase 2 interim data of AC Immune's AD vaccine, and the accepted IND for LION-101, an investigational gene therapy for Limb-Girdle Muscular Dystrophy Type 2I/R9.

Welcome to this special edition of Neurology News Network. I’m Marco Meglio. Please excuse our appearance this week as a majority of the US workforce, including the NeurologyLive team, moves to working remote as we come together to help reduce the spread of the novel coronavirus.

An advisory panel of experts convened by the Alzheimer’s Drug Discovery Foundation (ADDF) and the Association for Frontotemporal Degeneration (AFTD) recently published a paper providing recommendations on outcome measures and statistical considerations for the design of early drug trials for Alzheimer disease (AD), frontotemporal degeneration (FTD), and other neurodegenerative dementias.Among them included employing rigorous statistical analyses and procedures, incorporating the appropriate biomarker and clinical end points to reflect the drug’s mechanism of action in the specific study population, leveraging historical data to determine appropriate outcome measures, and considering novel clinical development plans to increase efficiency in moving a drug candidate or determining that it is ineffective as quickly as possible.

Data from an interim analysis of a phase 2 trial of AC Immune SA’s ACI-24 anti-amyloid-beta (Aß) vaccine for the prevention of Alzheimer disease (AD) suggest that the investigational agent is safe and well-tolerated in people with mild AD.The 18-month safety and tolerability analysis yielded no safety concerns. No evidence of central nervous system (CNS) inflammation or amyloid-related imaging abnormalities (ARIA) related to ACI-24 were seen in any participants. The phase 2 study will complete with a planned 24-month analysis of the currently enrolled participants. Andrea Pfeifer, PhD, chief executive officer, AC Immune SA, said in a statement that “...the optimized ACI-24 formulation represents a potential breakthrough in Abeta vaccination, as it elicits a strong immune response against oligomeric and truncated Abeta, the suggested key culprits in the Abeta pathway driving early Alzheimer’s disease.”

The FDA has cleared the investigational new drug (IND) application for Asklepios BioPharmaceutical’s LION-101, an investigational gene therapy for the treatment of Limb-Girdle Muscular Dystrophy Type 2I/R9 (LGMD2I/R9). The agent will now proceed into a phase 1/2 clinical study.The phase 1/2 study will assess single intravenous infusions of LION-101, a novel recombinant adeno-associated virus (rAAV) based vector, among adult and adolescent individuals with genotypically confirmed LGMD2I/R9, with the trial expected to begin dosing in the first half of 2022. Further details from the study have not been released.Asklepios Biopharmaceutical, a wholly owned and independently operated subsidiary of Bayer AG acquired in 2020, is a fully integrated AAV gene therapy company with an array of clinical trials using AAV gene therapy across a range of late-onset Pompe disease, multiple system atrophy, and Parkinson disease.

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