Phase 1b Trial Begins to Test Alector’s Immune-system Targeting Antibody AL003 in Alzheimer’s Patients
A Phase 1b trial has started dosing Alzheimer’s patients with Alector’s candidate immune system-targeting therapy, called AL003, to evaluate its safety and tolerability, the company has announced.
AL003 is an antibody which targets sialic acid binding Ig-like lectin 3 (SIGLEC 3, also known as CD33). SIGLEC 3 is found on a type of brain cell called microglia which act as the main form of immune defence in the central nervous system.
The antibody works by binding to SIGLEC 3 and stopping it from functioning, which allows microglia to function normally and possibly ease the severity or progression of Alzheimer’s.
SIGLEC 3 is also a known genetic risk factor for Alzheimer’s and mutations in this gene have been associated with an increased risk of developing Alzheimer’s disease.
“AL003 is intended to allow the brain’s immune system to simultaneously address multiple parallel pathologies involved in the progression of Alzheimer’s disease,” Arnon Rosenthal, PhD, CEO at Alector, said in a press release.
Researchers are now initiating the second part of the INTERCEPT trial (NCT03822208). This placebo-controlled study is evaluating AL003’s safety, tolerability, pharmacokinetics (essentially how the body affects a medicine), and pharmacodynamics (the interactions between the body and a compound).
The trial was divided into two phases. In the first, 42 healthy adults were given single-ascending doses of AL003 or a placebo. This allowed researchers to find the highest concentration of AL003 that can be administered safely.
“We evaluated the pharmacokinetics and pharmacodynamics of AL003 and found tolerable doses in a placebo-controlled, single-ascending dose escalation study in healthy volunteers,” said Robert Paul, MD, PhD, Alector’s chief medical officer. “We look forward to evaluating AL003 in Alzheimer’s disease patients in the Phase 1b study.”
In this second part, 12 patients with mild to moderate Alzheimer’s will be given multiple doses of AL003 to evaluate its safety and how well it’s tolerated. The researchers will also measure how the treatment gets distributed around the body, how well it binds to its target, and any specific biomarker changes in the blood or fluid in the brain/spinal cord (cerebrospinal fluid).
AL003 is Alector’s second Alzheimer’s therapy to reach clinical trials, its first being AL002, another brain immune-system targeting antibody. Both therapies are being developed in collaboration with AbbVie.