EFRONT Study Announced to Assess Genetic Mutations in FTD

Andrin Oswald, MD

Centogene, in partnership with Alector, has announced an observational study, named EFRONT, that will investigate the genetic mutations in patients with frontotemporal dementia (FTD). Announced in June 2021, the study anticipates genetically testing 3000 patients with FTD in Belgium, Germany, Greece, Italy, Portugal, Spain, and Turkey.¹

Centogene’s Bio/Databank will assist in identifying candidates. As of December 2020, the company’s real-world repository has logged over 3.9 billion weighted data points from 600,000 patients in 120 different countries. Alector, a clinical-stage biotechnology company, continues to pursue immunoneurology therapies and is developing a humanized recombinant monoclonal antibody, AL001, as a potential product candidate to treat FTD. The antibody is currently in phase 3 testing for FTD with a granulin mutation (FTD-GRN) and phase 2 for a C9orf72 mutation (FTD-C9orf72).²

An estimated 5% to 10% of patients with FTD have a mutation in the progranulin gene, and additional patients have another genetic cause, genetic data collection may help provide insight in both intervention and management, as no approved treatment options currently exist. Centogene’s Bio/Databank includes epidemiologic, phenotypic, and genetic data from the global population, allowing for different levels of data to analyze and understand FTD, as well as other hereditary diseases. 

“Over the past 15 years, Centogene’s genetic expertise and multiomic approach has brought diverse insights into rare neurogenerative diseases,” Andrin Oswald, MD, CEO, Centogene, said in a statement.¹ “I am excited to be teaming up with Alector for the EFRONT Study, which will accelerate the understanding of FTD significantly. The study will take full advantage of the power of Centogene’s unique Bio/Databank, expertise in neuroscience, and extensive network of neurologists—increasing the body of degenerative neuroscience data available, and further expanding Centogene’s Bio/Databank for discovering the breakthroughs of tomorrow.”

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In conversation with NeurologyLive, Oswald discussed the clinical insights anticipated with the EFRONT study. Oswald noted that once 4000 patients with FTD have fully analyzed data, information may be gleaned on how to look at and treat patients, in addition to the potential role of the AL001 antibody as a therapy. Therapeutic modalities may be a viable treatment route, and gene therapy technology may work with a combination of other tools to better understand rare diseases such as FTD. According to Oswald, in collaboration with neurologists, Centogene is able to identify patients, conduct full genome sequencing, assess collected data, and then consequently select eligible patients for the Alector’s phase 3 study.

“Frontotemporal dementia is a devastating disease for which new treatment options are urgently needed,” Robert Paul, MD, PhD, chief medical officer, Alector, said in a statement.¹ “In line with our commitment to improving the lives of patients with frontotemporal dementia, we are pleased to support Centogene’s efforts to advance a better and more comprehensive understanding of the genetic underpinnings of FTD through the observational EFRONT Study.”

Additional research will be required concerning treatment for FTD and other related disorders, which may be aided by findings from the EFRONT study, according to Oswald. Multiomic assessment is crucial in understanding cell and pathway complications, as genetic mutation is only one element of a larger disease pattern. 

The first patient dosed with AL002—another investigational therapy in Alector’s pipeline, this being assessed in Alzheimer disease—randomized, double-blind, placebo-controlled, dose-ranging, phase 2 INVOKE-2 study was announced in February 2021. INFRONT-3, another randomized, double-blind, placebo-controlled, phase 3 clinical trial, dosed its first patient in July 2020, evaluating the effectiveness of a third investigational therapy, AL003, in people with or at risk for FTD due to progranulin gene mutation.³

REFERENCES

1. Centogene initiates EFRONT study to identify patients with genetic forms of frontotemporal dementia. News release. Centogene. June 2, 2021. Accessed July 14, 2021. https://www.globenewswire.com/news-release/2021/06/02/2240202/0/en/CENTOGENE-Initiates-EFRONT-Study-to-Identify-Patients-With-Genetic-Forms-of-Frontotemporal-Dementia.html
2. AL001. Our Science. Alector website. Updated 2021. Accessed July 14, 2021. https://alector.com/our-science/#pipeline
3. Alector doses first patient in pivotal phase 3 INFRONT-3 trial evaluating AL001 in patients with frontotemporal dementia. News release. Alector. Published online July 24, 2020. Accessed July 14, 2021. https://investors.alector.com/news-releases/news-release-details/alector-doses-first-patient-pivotal-phase-3-infront-3-trial