Benzinga | Jul 28, 2020 06:01PM EDT

Alector Reports Prelim. Data From AL001 Phase 1b, 2 Open-Lable Long-Term Dosing Study Of People With Frontotemporal Dementia: Study Resulted In Sustained Restoration Of Plasma Progranulin Levels; Phase 3 Study Initiated In Jul.

Alector, Inc. (NASDAQ:ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, today announced preliminary data from its Phase 1b and open-label Phase 2 studies of AL001, for the treatment of people with frontotemporal dementia with a progranulin gene (GRN) mutation (FTD-GRN). AL001 is the company's wholly owned, investigational human monoclonal antibody designed to modulate progranulin, a key regulator of immune activity in the brain. The data were presented today at the virtual 2020 Alzheimer's Association International Conference (AAIC) by Robert Paul, M.D., Ph.D., chief medical officer of Alector.

Frontotemporal dementia is a rapidly progressing and severe form of dementia found most frequently in people less than 65 years old at the time of diagnosis. There are multiple heritable forms of FTD, and FTD-GRN represents 5% to 10% of all people with FTD. There are currently no FDA-approved treatment options for FTD.

"We continue to discover and develop therapies in pursuit of our goal to eradicate neurodegenerative diseases," said Arnon Rosenthal, Ph.D., co-founder and chief executive officer of Alector. "The encouraging results from the Phase 1b and Phase 2 studies of AL001 represent substantial progress. With our rapid initiation of a pivotal Phase 3 trial, we hope that it is only a matter of time before AL001 is the first treatment option for people living with this devastating disease."

The ongoing Phase 2, multicenter, open-label, study is evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), fluid and imaging biomarkers and the effect on clinical outcome assessments of AL001. The Phase 2 study is expected to enroll up to 40 participants who will receive treatment with AL001 for up to 96 weeks. The study has completed enrollment of 10 symptomatic patients with FTD-GRN and 5 asymptomatic individuals carrying a GRN mutation. Enrollment for FTD patients with C9orf72 mutations is currently ongoing.

Due to the COVID-19 pandemic, several clinical sites for the Phase 2 study were temporarily closed or conducted reduced or remote patient assessments during the evaluation period. As a result, some participants missed a dose of AL001 or missed clinical assessments during the treatment period. Alector is working closely with the sites, investigators and participants to manage future effects of the COVID-19 pandemic on the study.

"AL001 was well-tolerated and caused sustained restoration of plasma progranulin levels in all FTD-GRN participants back to normal levels. These preliminary findings are encouraging and also suggest that long-term treatment with AL001 has the potential to slow disease progression in patients with FTD-GRN as measured by relevant disease biomarkers," said Dr. Paul. "Although the COVID-19 pandemic impacted data collection for this initial analysis, we believe these early results are quite promising. We continue to advance the Phase 2 study and would like to thank the participants, their families and our study collaborators for their support in advancing AL001 forward."

A summary of the preliminary results from the Phase 2 study are as follows:

* A total of 15 participants with symptomatic and asymptomatic FTD-GRN have been evaluated in the Phase 2 study as of May 14, 2020.

* AL001 was observed to be generally safe and well-tolerated. There were no treatment-related serious adverse events observed in participants receiving AL001 treatment.

* AL001 led to sustained restoration of plasma progranulin levels in all FTD-GRN participants back to the normal range.

* Preliminary data from the symptomatic FTD-GRN participants showed a decrease in plasma NfL levels from baseline in the majority of participants at the last measured time point.

* In the presented case study of a symptomatic FTD-GRN participant, with the longest continuous treatment with AL001 for over 28 weeks, treatment resulted in a sustained decrease in plasma NfL by 29% from baseline.

These early data suggest that longer term treatment with AL001 could lead to sustained increase in PGRN and sustained reduction in plasma NfL over time. Alector plans to present additional Phase 2 data highlighting clinical and biomarker endpoints in the future.

In July 2020, Alector announced that the first patient was dosed in INFRONT-3, a global, pivotal Phase 3 trial evaluating the efficacy and safety of AL001 in symptomatic and pre-symptomatic people with FTD-GRN. AL001 has received Fast Track and Orphan Drug designations from the U.S. Food and Drug Administration for FTD.