On 27 October, Alector announced the completion of target enrolment to INFRONT-3, their Phase 3 trial of latozinemab for a heritable form of frontotemporal dementia, linked to mutations in the progranulin gene (FTD-GRN). INFRONT-3 is evaluating the safety and efficacy of latozinemab in slowing disease progression, aiming to recruit 90-100 symptomatic participants with FTD-GRN. Recruitment has now been completed, with 101 participants from north America, Europe, Argentina and the Asia-Pacific region. FTD is a rare neurodegenerative disease that affects over 100,000 people in Europe. There are many different forms of FTD, and one of the most common heritable forms of FTD is caused by mutations in the progranulin gene. Progranulin is a key regulator of immune activity in the brain, and loss-of-function mutations in the progranulin gene causes inflammation and progressive loss of brain cells, leading to FTD.
Alector’s drug Latozinemab, which is being developed in collaboration with GSK, is a monoclonal antibody designed to block sortilin, a protein that is involved in the degradation of progranulin. Latozinemab was designed to slow down the degradation of progranulin, thereby enhancing the activity of microglia, the primary cells of the brain’s innate immune system. INFRONT-3 is a pivotal, randomised, double-blind, placebo-controlled Phase 3 clinical trial, which is enrolling symptomatic and at-risk participants with FTD-GRN. Participants are randomized to receive latozinemab or placebo intravenously every four weeks for the duration of the 96-week trial and are being given the option to continue receiving treatment in the open-label extension (OLE) study after the 96-week treatment period. The primary endpoint in INFRONT-3 is disease progression as measured by cognitive and functional scales that assess the severity of FTD. INFRONT-3 will also assess progranulin levels in cerebrospinal fluid and plasma, mapping how levels change in response to treatment and in relation to FTD symptoms. Read the Alector press release:
