GM604 for ALS

Last updated Nov 15, 2024, by Marisa Wexler, MS
Fact-checked by Ines Martins, PhD

What is GM604 for ALS?

GM604 is an experimental therapy that’s designed to slow disease progression in people with amyotrophic lateral sclerosis (ALS). It’s given via intravenous injection into the bloodstream, but it may no longer be in development for ALS.

The therapy, which was developed by Genervon, completed an ALS Phase 2a clinical trial in 2014. The company said in 2023 it was working to obtain funding and a potential partner to advance GM604 into a Phase 3 clinical trial, which would continue to explore its effectiveness in ALS patients. No further updates related to GM604 have been issued to date, however, so it’s not clear if its development is still ongoing.

Also known as alirinetide, GM604 received fast track and orphan drug designations in the U.S. as a potential treatment for ALS. GM604 also was granted orphan drug status in Europe. All of these designations provide a range of incentives to help companies advance the development of treatments with the potential to fill unmet medical needs.

GM604 was also being explored as a potential treatment for other neurological disorders including Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, and spinal cord injury. Depending on which condition is being discussed, GM604 could also be referred to as GM6, or by other names.

Therapy snapshot

How does GM604 work in ALS?

ALS is characterized by the dysfunction and death of motor neurons, the specialized nerve cells that control voluntary movement.

GM604 is a peptide made of six amino acids, which are the building blocks of proteins, that’s identical to one of the active sites of human motoneuronotrophic factor (MNTF), a signaling molecule that interacts with multiple receptors to help coordinate the development of the nervous system.

Preclinical data have suggested that, by mimicking MNTF, GM604 can act on a number of different biological pathways at the same time. Specifically, it acts to protect nerve cells and promote the growth of new nerve fibers, reduce inflammation, and modulate the activity of dozens of genes that have been implicated in ALS.

How will GM604 be administered in ALS?

GM604 is administered by a slow injection into the bloodstream, lasting about one minute. In a Phase 2a clinical trial, patients received six injections containing 320 mg of the therapy over two weeks.

GM604 in ALS clinical trials

GM604 was first tested in ALS in GALS-001, a proof-of-concept Phase 2a clinical trial (NCT01854294) that enrolled 12 adults with ALS who had been living with the disease for two years or less.

The participants were randomly assigned to receive six injections of 320 mg of GM604 or a placebo, given three times a week (Monday, Wednesday, and Friday) over two consecutive weeks. The study lasted 12 weeks, during which participants could continue to receive the standard ALS treatment riluzole, which is sold as Rilutek, among others.

The main goals were to assess the treatment’s safety and tolerability, as well as its effect on ALS-related biomarkers. The therapy was well tolerated overall, with no serious side effects determined to be related to treatment.

Compared with a placebo, GM604 resulted in significant decreases in blood levels of several ALS biomarkers, including the disease-related proteins SOD1, TDP-43, and tau. Similar trends were seen for levels of these biomarkers in cerebrospinal fluid, which is the liquid around the brain and spinal cord, though most differences didn’t reach statistical significance.

Scores on the ALS Functional Rating Scale-Revised (ALSFRS-R), a measure of functional ability used to track ALS disease progression, tended to worsen more slowly while on GM604 compared with progression rates before the trial. While the difference between the GM604 and placebo groups wasn’t significant, the findings still lend some credence to the idea that GM604 may help slow the progression of ALS.

These findings were published in 2017 and no other updates have been released. It’s not known if GM604 is still being developed for ALS.

Common side effects of GM604

Based on data from the completed Phase 2a study, the most common adverse events observed during treatment with GM604 included:

• falls
• pain at the puncture site
• rash
• headache.

All these adverse events, except for rash, were also reported in some patients given a placebo, so more data would be needed to better understand GM604’s safety profile.

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