AT-1501 (anti-CD40L) is an experimental therapy to treat amyotrophic lateral sclerosis (ALS). Anelixis Therapeutics, a subsidiary of the ALS Therapy Development Institute (ALS TDI), originally was developing the treatment. Novus Therapeutics subsequently purchased Anelixis and is continuing the development of AT-1501.

How AT-1501 works

ALS is a progressive neurodegenerative disease for which there currently is no cure. The symptoms of the disease are the result of damage to and death of motor neurons (nerve cells that control the movement of muscles). While the exact cause of the disease is not clear, researchers think the immune system may contribute to its progression by causing inflammation in the nervous system, leading to damage to motor neurons. 

AT-1501 is an antibody against a protein called CD40 ligand (CD40L). Antibodies are proteins that bind to and block a particular target. CD40L is present on the surface of some immune cells. It is a protein that plays a role in regulating the immune response and that can trigger inflammation in the spinal cord. Research has shown that the CD40L pathway is overactive in ALS patients.

The exact mechanism of action of AT-1501 in ALS is not clear, but researchers think that by inhibiting CD40L, the potential therapy could block or delay the activation of the damaging inflammatory immune response. This could delay the onset or slow the progression of ALS and increase survival. 

AT-1501 in clinical trials

Researchers extensively studied AT-1501 in preclinical trials with positive results.

For example, a preclinical study using a mouse model of ALS has shown that AT-1501 significantly increased the time until disease onset in the animals, increased their survival, and improved their body weight, compared with mice that received a placebo. The results of this study were published in the scientific journal Nature Genetics.

In the wake of those results, studies testing the safety of AT-1501 in non-human primates took place in 2017. The studies also produced positive results for safety.

Researchers then tested AT-1501 in a Phase 1 clinical trial in humans. The trial enrolled healthy volunteers and eight ALS patients to test the safety and tolerability of the treatment. Results of the trial showed that all participants tolerated all dose levels in the trial well. The pharmacokinetics (movement in the body) of the treatment was as the researchers predicted. 

Following the results of the Phase 1 trial, Novus initiated a Phase 2a trial (NCT04322149). The trial is recruiting 54 adult patients with ALS to take part in the open-label, multidose study at Johns Hopkins University Medical Center in Baltimore, Maryland. Additional trial sites in California, Georgia, and Indiana will be opening soon.

Participants will receive one of three increasing intravenous doses of AT-1501 once every two weeks for 11 weeks. Investigators will continue to monitor them for safety and tolerability for another eight weeks (19 weeks in total). Novus announced in November 2020 that it dosed the first patient in the trial. The company estimates concluding the trial in October 2021.

Other information

The U.S. Food and Drug Administration granted AT-1501 orphan drug designation. This designation provides companies benefits such as tax credits for clinical trials while they are developing treatments for rare disorders.

 

Last updated: Dec. 11, 2020

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