- Amylyx Pharmaceuticals has developed a drug that could slow the fatal neurological disease ALS.
- It's set to seek approval this year in Canada and Europe, but the FDA has asked for another trial.
- That means people with ALS in the US will have to wait to get access to the promising treatment.
In the four years since Corey Polen was diagnosed with the neurological disease amyotrophic lateral sclerosis, or ALS, the disease has stolen his ability to type with his hands and attacked his vocal cords.
It's also stealing time from him. ALS is fatal; it generally kills people three to five years after symptoms begin.
There's a promising new treatment on the horizon. A drug developed by Amylyx Pharmaceuticals, a startup in Cambridge, Massachusetts, cut a person's risk of death by 44% over three years, an analysis of long-term data from a mid-stage trial found.
The trial data was so exciting that the ALS Association and another patient group, for the first time, publicly petitioned the US Food and Drug Administration to approve the drug right away.
The clinical-trial data seems to be good enough for regulators abroad. Amylyx is asking Canada's and Europe's drug agencies to approve the treatment this year.
But in a surprise to the ALS community, the FDA has asked Amylyx to run another clinical trial before submitting the treatment for approval, the company said on Wednesday. Amylyx's cofounders, Joshua Cohen and Justin Klee, said the decision would upset people with ALS.
"I'm sure the question will be asked: Why was the data sufficient in Canada and not the US?" Cohen told Insider. "Our goal is to get it to as many patients as quickly as possible. Unfortunately, that means some territories may get it sooner than others."
The decision means Amylyx's treatment likely won't come soon enough to help Polen. Amylyx's mid-stage trial was two years long before it was extended. The study that the FDA requested, called a phase-three trial, would likely take longer.
"If the FDA requires a phase 3, then I will die before I can access it," Polen wrote in an email ahead of Amylyx's update, using software that tracks his eye movement to type. "Amylyx is an American business. They ran this trial under the FDA with FDA-designated benefits. They received funds from American donations. The failure to file for approval in America speaks loudly to the failure of the FDA."
The FDA is known as more nimble than other drug agencies, but it has puzzled people with ALS
ALS, also called Lou Gehrig's disease after the baseball player who died from it, affects 25,000 to 30,000 Americans. It attacks nerve cells and decimates a person's ability to control muscles needed to eat, speak, and breathe.
Amylyx's drug, AMX0035, appears to slow down the disease. Trial participants who took the drug lived 6 1/2 months longer, on average, than those who got a placebo — Neil Thakur, the ALS Association's chief mission officer, said that's a huge win against a disease that kills people in a few years. That result was unlike anything the ALS community has seen from a drug trial in a long time, he added.
The trial also met new testing guidelines the FDA published last year, Cohen said. The agency had laid out to drug companies what it would like to see in a trial in order to approve a drug, including the minimum testing time and the measurements of the drug's effect.
The FDA was excited by Amylyx's data but wants to Amylyx to follow the standard protocol, testing how well new drugs work in multiple trials, Cohen said.
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"The FDA is reticent to do single-study approvals unless it's an unbelievable, miraculous result," he added.
The FDA did not respond to a request for comment.
The agency's reaction has puzzled the ALS community. The FDA has historically been more nimble than its Canadian and European counterparts, moving faster and bending the rules for other rare-disease drugs. Why would regulators dig their heels in now?
Sandy Morris, an ALS patient and advocate, told Insider that she and others felt that they were being "protected to death" by the FDA. The agency wants to see multiple trials with stellar results, but Morris said she'd be content with a moderate treatment for her fatal disease.
"We have a drug that met its primary endpoint for function, but the FDA is not seeing a way to be flexible," Thakur said. "If it turns out that some people who go to a different country get better treatment, I mean, I can't imagine anyone being OK with that and thinking that's a good solution."
Desperate patients may try to DIY the drug, one advocate says
Without early approval of AMX0035, people with moderate or advanced ALS don't have many other options for extending their life.
It's difficult for many people with ALS to enroll in a drug trial. Clinical tests like Amylyx's often focus on people in the earlier stages of the disease, meaning those who began experiencing symptoms within the past 18 months.
People who aren't eligible for clinical trials can sometimes access experimental drugs through a special FDA program for terminal diseases called compassionate use. But that's far from a guarantee. Biogen, another developer of an ALS drug, is facing heat after rejecting a request for special access to its ALS drug, tofersen.
Al Sandrock, Biogen's executive vice president of R&D, said in an open letter that offering tofersen outside of a clinical trial could interfere with the biotech's eventual FDA application.
Cohen and Klee have not decided whether Amylyx will offer compassionate use of AMX0035 to people with late-stage ALS.
"These two conversations, though distinct, share one thing in common, and that is frustration with the system," said Ken Menkhaus, a political-science professor and ALS Association board member who was diagnosed with ALS in 2018.
Menkhaus is concerned that the decision to require Amylyx to do another trial will erode patients' views of the FDA, changing it from an agency that works to protect them to one that stands in their way.
Amylyx's treatment combines two drugs that are already on the market. Menkhaus said he had heard chatter of people mixing their own batches of AMX0035 and predicted that American patients with no other options may opt to DIY the drug following this week's regulatory update.
"My only hope is that the dosage is done right and people don't get hurt," he said.