Rare Daily Staff

Alector said it initiated patient screening and enrollment for a mid-stage clinical trial for AL001, its experimental treatment for people with frontotemporal dementia (FTD) with specific genetic mutations.

FTD is a rapidly progressing and severe form of dementia found most frequently in individuals less than 65 years old at the time of diagnosis. It affects 50,000 to 60,000 individuals in the United States and roughly 110,000 individuals in the European Union, with potentially higher prevalence in Asia and Latin America. There is currently no approved treatment available for FTD patients.

There are multiple heritable forms of FTD. In one form, FTD-GRN, patients have a mutation in the progranulin gene. This population represents between 5 percent and 10 percent of all patients with FTD. Mutations in a single copy of progranulin leads to a 50 percent or greater decrease in the level of progranulin and invariably leads to development of FTD. To date researchers have identified more than 70 inherited loss of function mutations in the progranulin gene that lead to FTD. In another form, FTD-C9orf72, people with mutations in the C9orf72 gene can develop FTD, which represents 5 percent to 10 percent of all patients with FTD. FTD-C9orf72 is associated with abnormal accumulation of the protein TDP-43, which is also a hallmark in FTD-GRN.

AL001 is a human monoclonal antibody designed to modulate progranulin, a regulator of immune activity in the brain with genetic links to multiple neurodegenerative disorders, including FTD, Alzheimer’s disease, and Parkinson’s disease. It aims to increase the level of progranulin in humans by inhibiting a progranulin degradation mechanism.

The phase 2 trial will assess the longitudinal safety, tolerability, pharmacokinetics and pharmacodynamics of AL001, as well as its effects on biomarkers of neurodegeneration and on cognition. The study will enroll patients with granulin gene mutation and an additional cohort of FTD patients with a C9orf72 mutation.

“We are encouraged by the recent data from our phase 1b trial of AL001, in which AL001 was well-tolerated and restored progranulin back to normal physiological levels in the central nervous system of FTD-GRN patients,” said Robert Paul, chief medical officer of Alector. “In this phase 2 trial, we plan to enroll up to 32 patients and gain important insights into AL001’s safety and activity in this patient population as we prepare for our pivotal phase 3 study in 2020.”

Photo: Robert Paul, chief medical officer of Alector

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