AL001 Receives Orphan Drug Designation by FDA for Frontotemporal Dementia


The human recombinant monoclonal antibody is designed to increase progranulin levels to sustain neuron survival and moderate inflammation.

Dr Robert Paul

Robert Paul, PhD, MBA, the chief medical officer at Alector

Robert Paul, PhD, MBA

AL001, a human recombinant monoclonal antibody, for the treatment of patients with frontotemporal dementia (FTD) has been granted an Orphan Drug designation by the FDA, Alector has announced.

The therapy is designed to increase levels of progranulin to sustain neuron survival and moderate inflammatory response by blocking the breakdown of progranulin.

“There are currently no approved therapies to address the underlying cause and needs of FTD patients. In addition, given the marked behavioral and personality changes associated with FTD, coupled with the early onset of the disease, the care of FTD patients is a significant challenge for families and the society,” said Robert Paul, PhD, MBA, the chief medical officer at Alector.1 “The granting of orphan drug designation is a significant milestone for the AL001 development program, and we are excited to work with leaders and experts in the research, medical and patient advocate communities to bring AL001 to the patients suffering from this disease.”

A subset of the estimated 200,000 with FTD only have a single functioning gene that directs progranulin production, according to Alector, bringing their levels of the protein to less than half of their normal counterparts. Paul called this group an ideal one to begin testing the therapy’s mechanism of action, as their disorder is clearly caused by a lack of the protein. This patient group is considered the most likely to show a high rate of response to the treatment compared with other FTD patients, he said.2

If the therapy receives approval, patients would need to take the therapy for the remainder of their lives to sustain their progranulin levels, according to Alector. The company also acknowledged that if AL001 is successful, it plans to explore progranulin elevation in a broader FTD population.

The therapy’s development stems from a recent Series E financing of $133 million, coming from a group consisting of Deerfield Management, AbbVie Ventures, Federated Kaufmann Fund, Section 32, Euclidean Capital, Foresite Capital, Lilly Asia Ventures, New Leaf Venture Partners, Perceptive Advisors, Casdin Capital, Polaris Partners, OrbiMed, MRL Ventures, GV, the Dementia Discovery Fund, Mission Bay Capital, Amgen Ventures, and others. The total fundraising effort totaled $415 million.

At the time, Arnon Rosenthal, PhD, the chief executive officer at Alector, said that empowering the immune system could provide as much benefit as immuno-oncology therapies have for patients with cancer.3 Findings of recent human genetics studies have suggested that neurodegenerative diseases are developed in part because of dysfunction in the immune system in the brain, prompting Alector’s development of immuno-neurology drugs to counteract multiple pathologies at once.

“FTD is caused in part by a dysfunctional brain immune system, and AL001 is one of our immuno-neurology drugs designed to repair that immune system to elicit a therapeutic benefit,” said Rosenthal in a statement. “We believe that our immuno-neurology approach could potentially have as much impact on brain disorders as immuno-oncology drugs have had on cancer patients.”

In addition to AL001, Alector is also developing 2 more drugs in the Alzheimer space, AL002 and AL003. AL002 targets a triggering receptor expressed on myeloid cells 2 (TREM2), a known contributor to the development and progression of Alzheimer’s disease and other neurodegenerative disorders, while AL003 targets SIGLEC-3, a transmembrane receptor expressed on cells of myeloid lineage, a prevalent risk factor for Alzheimer’s disease.

“There are currently no FDA-approved treatments that can make a direct impact on the progression of Alzheimer’s disease or FTD,” said Thomas C. Südhof, MD, PhD, a professor at the Stanford University School of Medicine and the recipient of the Nobel Prize in Physiology or Medicine, in July. Südhof, an incoming member of Alector’s Scientific Advisory Board, said that “bold, new ideas are imperative to address these significant patient populations that are in great need of treatment options.”


1. Alector Receives Orphan Drug Designation from the U.S. FDA for AL001 for the Treatment of Frontotemporal Dementia [press release]. South San Francisco: Alector; July 25, 2018. Accessed August 8, 2018.

2. Alector Snags $133M to Activate Immune Cells Against Neurodegeneration. Xconomy website. Published July 25, 2018. Accessed August 8, 2018.

3. Alector Announces $133 Million in Series E Financing to Advance Broad Portfolio of Immuno-Neurology and Immuno-Oncology Programs [press release]. South San Francisco: Alector; August 8, 2018. Accessed August 8, 2018.

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