Weeks after GlaxoSmithKline ponied up $700 million to work with Alector on a pair of “immuno-neurology” drugs, the neurodegenerative disease biotech pulled the curtain on early data showing its approach could slow the progression of an inherited form of dementia.
The phase 2 data come from just nine patients with frontotemporal dementia (FTD) stemming from a mutation in the progranulin gene. This gene codes for a protein of the same name that plays a role in neuronal health and the function of lysosomes—organelles involved in removing waste from cells. Low progranulin levels are a known cause of FTD, a quickly progressing type of dementia that typically strikes in a person’s 40s or 50s.
The study found that the drug, AL001, given once a month, restored progranulin to normal levels in the blood and cerebrospinal fluid of seven of 12 patients with symptomatic dementia. The data were presented on Thursday at the Alzheimer’s Association International Conference.
The study is also testing the drug in patients with the progranulin mutation who have not yet developed symptoms and in patients with FTD who have a mutation in a different gene, C9orf72. Patients will be treated with AL001 for 96 weeks, or nearly two years.
The study was geared to gauge the safety and tolerability of the treatment and not to measure clinical benefit, but comparing the patients’ scores on a measure of dementia symptoms to those of a historical control group offers a peek at its potential efficacy.
The study found that treatment with AL001 slowed disease progression by 47% when compared to a matched group from a study run by the Genetic FTD Initiative. The control group posted a 6.4-point increase on a measure of dementia symptoms over one year, while the scores of patients who received AL001 worsened by 3.4 points over one year.
“Though this is a small open-label study, the totality of the data presented from the INFRONT-2 Phase 2 study paint an encouraging picture of AL001’s potential to slow disease progression in patients with FTD, a devastating disease for which there are currently no approved treatment options,” said Alector Chief Medical Officer Robert Paul, M.D., Ph.D., in a statement.
“Chronic treatment with AL001 demonstrated durable, on-target activity with a complete reversal of the progranulin deficiency that is causing disease. The effect of AL001 treatment on clinical disease progression, and consistent improvements observed across diverse biomarkers, strengthen our confidence that AL001 is working as designed,” Paul added.
AL001 is also in a phase 3 trial in people with a progranulin mutation who are at risk of developing FTD or are already showing symptoms. The treatment, along with a second “immuno-neurology” asset, AL101, was the focus of a development and commercialization deal that saw GSK hand over $700 million upfront and promise as much as $1.5 billion if all goes to plan and both meds get to market.
Rather than target the buildup of toxic proteins like amyloid beta, the treatments are designed to harness the body’s own immune system to fight neurodegenerative disease.