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A combination of two experimental drugs appears to slow the decline of patients with amyotrophic lateral sclerosis, an illness often known as ALS or Lou Gehrig's disease.
A six-month study of 137 patients with a fast-progressing form of the disease found that those who got daily doses of a two-drug combination called AMX0035 scored several points higher on a standard measure of function, a team reports in the Sept. 3 issue of The New England Journal of Medicine.
The difference was modest but meaningful to patients, said Dr. Sabrina Paganoni. She's the lead author and a researcher at the Sean Healey & AMG Center for ALS at Mass General and Harvard Medical School.
"They want to be able to continue to use their hands so they can cut their own food and type emails, or they want to be able to walk and climb stairs," Paganoni said. "And this is exactly what we measured in the trial."
The results are far from a cure. Even so, "I am convinced that we are at the beginning of a new era in ALS treatment discovery," Paganoni said.
"There's great hope for disease-modifying treatment," added Tania Gendron, who studies neurodegenerative diseases at the Mayo Clinic in Jacksonville and was not involved in the study. "In the next few years, I think there are going to be some big discoveries."
ALS destroys the nerve cells that control muscle movement. Patients typically become disabled and die within five years of their diagnosis.
For decades, the only drug approved by the Food and Drug Administration for ALS was riluzole, which has been on the market since 1995 and has been shown to extend the lives of patients. Then in 2017, the FDA approved edaravone, which helps some patients retain function longer.
AMX0035 works by protecting nerve cells from two types of damage that are hallmarks of ALS. And in the study, it produced a benefit, even though many of the patients were already taking riluzole and edaravone.
It appears that the new and old drugs all work in different ways to slow down the disease, Paganoni said. "We think ultimately we will need a combination of treatments to effectively fight ALS."
It's not clear yet whether AMX0035 extends life or maintains muscle strength. And ordinarily, at least one larger study would be required before the FDA considered approving the drug.
But the ALS Association along with the advocacy group I AM ALS have joined forces to petition the FDA to make an exception.
"In ALS, a trial like this would probably take about three years," said Neil Thakur, chief mission officer of the ALS Association. "And so the question for the whole community is what do we gain for that three-year study?"
The ALS Association helped fund the research on AMX0035 and has a limited financial stake in its success. The group's main concern, though, is patients who won't live long enough to wait for another study, Thakur said.
"That's why we're thinking the best thing to do for the community is to make this drug available sooner and let everyone have it as a treatment option as soon as possible," he said.
AMX0035 has taken a highly unusual path toward approval.
It was developed by Amylyx, a tiny company founded by a couple of college students, Josh Cohen and Justin Klee, who are still in their 20s. The pair were working late one night in the company's Cambridge, Mass., office when they learned the results of the ALS study.
"When the statisticians called, you could hear their whole firm cheering in the background," Cohen said. "So we knew before they said the numbers that something good had happened."
But their elation was mixed with a sense of responsibility, Klee said.
"While these results are great, it's not a cure, and so we and others in the whole community need to keep pushing forward until we get cures," he said.
That's beginning to look more likely than it did even a few years ago, the Mayo Clinic's Gendron said.
One reason is that scientists are discovering new biological markers that appear in the blood or spinal fluid of ALS patients. These markers will allow earlier diagnosis when treatments are more likely to work, Gendron said. They will also help select which patients to give a particular drug and allow researchers to know whether the drug is reaching its intended target.
Another reason for optimism is the sheer amount of research going on.
"What makes this time so exciting is there are over 50 different clinical trials that are enrolling and recruiting ALS patients right now," said Kuldip Dave, the ALS Association's vice president of research. "And they're all going after different targets."