Amylyx's neuron-protecting drug slows ALS decline in late-phase study

A novel combination of compounds has shown that it can help slow down the progression of amyotrophic lateral sclerosis, known as ALS, by supporting the inner workings of the brain’s neurons.

After six months of treatment, Amylyx Pharmaceuticals’ AMX0035 demonstrated a significant benefit compared to placebo, delaying the fast-acting neurodegenerative disease that robs patients of their ability to talk, swallow, and eventually move and breathe.

Using a common clinical metric for gauging patients’ abilities to walk, dress and feed themselves—the Revised ALS Functional Rating Scale, or the ALSFRS-R—the company’s phase 2/3 study showed that participants taking AMX0035 lost fewer points over time. 

The trial, funded in part with money raised by the ALS Ice Bucket Challenge and with support from the ALS Association and ALS Finding a Cure, had its results published in The New England Journal of Medicine.

The rating scale adds up points across 12 different categories, for a total score of 48, with higher numbers indicating better function. The average rate of decline was -1.24 points per month for patients taking AMX0035, compared to -1.66 points per month with placebo. That added up to treated patients scoring 2.32 points higher after 24 weeks of the oral therapy.

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“If you look at the questions, each one-point drop is very significant,” Amylyx co-founder and co-CEO Justin Klee said in an interview. “For example, if you look at speech, you can quickly go from speaking with issues, to not being able to speak at all. Or you might go from changing the type of food you eat, to needing a feeding tube. The drops are quite dramatic.”

The drug’s effects were seen across all the main types of questions on the scale—which suggests the treatment works broadly across the nervous system, Klee said—but the most sensitive categories appeared to be the ones related to fine motor skills.

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“In some ways that’s the most important, because that's if the patient can feed themselves, or if they can type on a laptop—it's how you interact with the world,” he said.

AMX0035 is a combination of sodium phenylbutyrate—a booster of the endoplasmic reticulum, which works to correctly fold necessary proteins within the cell—and taurursodiol, which aims to protect neurons’ energy-producing mitochondria. 

In addition, the drug and placebo were given alongside any other approved therapies being taken by the study’s 137 participants, said Amylyx’s second co-founder and CEO, Josh Cohen.

“We see this data as being on top of the current care patterns in ALS, so it’s an advance beyond what we have, rather than just head-to-head with placebo or another treatment,” Cohen said. “Our prespecified, primary outcome [the ALSFRS-R] has been a very high bar in ALS.”

The drug also showed certain benefits among secondary measurements, with treated patients being hospitalized less often as well as slower declines in lung function and loss of muscle strength. Meanwhile, its safety was comparable to placebo, with fewer reports of serious side effects.

“What we're trying to do now is work very closely with the FDA to try to move AMX0035 forward as quickly as possible,” Cohen said.

AMX0035 is also being studied in people with Alzheimer’s disease and mild dementia. A separate phase 2 study completed its enrollment earlier this summer, and Amylyx expects to report results in early 2021.