Patients with amyotrophic lateral sclerosis, a debilitating and fatal neurological disease, have few treatment options. The scarcity helps explain why an experimental drug attracted attention earlier this year, as a small study found its use appeared to slow functional decline in people with rapidly advancing ALS.
On Friday, the drug known as AMX0035 came back into the spotlight. Further analysis showed that, since the start of the study, patients who initially received it lived a median six and half months longer than those who didn't. Across 135 evaluable patients, median survival was 25 months in the drug-treated group versus 18.5 months in the placebo arm, according to data published in the journal Muscle & Nerve.
"This is a remarkable effect," said Sabrina Paganoni, the study's principal investigator and the co-director of the Neurological Clinical Research Institute at Massachusetts General Hospital. "These patients have very rapid progression. To be able to modify their survival by several months is fantastic."
Amylyx Pharmaceuticals, the Cambridge, Massachusetts-based biotech that's developing AMX0035, said the new survival results and the functional data seen earlier support the company's plan to quickly advance its drug. Co-founders Josh Cohen and Justin Klee told BioPharma Dive in September that they've been in talks with regulatory agencies in the U.S., Europe and Canada.
AMX0035 could be a welcome addition for ALS patients. In the U.S., treatment is essentially limited to two drugs: Radicava, which was approved in 2017 and developed by Mitsubishi Tanabe Pharma, and riluzole, a decades-old medicine and the only one proven to have some level of survival benefit — typically a few months.
"If that drug was available right now, all my patients would get it. There's no question," said Jeffrey Rothstein, director of the Robert Packard Center for ALS Research at the Johns Hopkins University School of Medicine. Rothstein also served as an investigator for the key study of AMX0035, called CENTAUR.
While Amylyx's drug has drummed up excitement, researchers acknowledge that it's no cure. Patients who took it still experienced functional declines and, even with treatment, the estimated probability of living to two years post study enrollment was about 50%.
The study was also relatively small and limited to just a certain kind of ALS patient, putting pressure on the company to run larger, longer investigations with a wider variety of patients.
"I'm a big believer that you need to do it twice," especially since many drugs for neurological conditions fail when tested again, Rothstein said. Indeed, the last couple years have seen a steady stream of drugs meant to treat diseases of the brain or nervous system fail in the later stages of clinical testing.
ALS drug research hasn't yielded many successes either, with Radicava being the first treatment to gain approval in quite some time. Notably, that drug was cleared based on functional data similar to what Amylyx has collected.
Researchers hope that a deeper understanding of ALS and the ways in which it develops could lead to a sea change in treatment in the not-too-distant future. One approach in particular — that of silencing the genes thought be responsible for some patients' ALS — has been gaining steam. This summer, the New England Journal of Medicine published positive clinical data on a drug in development at Biogen, the world's largest neuroscience biotech.
Genetic therapies likely won't work for everyone, though.
"There are several different disease mechanisms that contribute to ALS," Paganoni said. "So perhaps, all we need to do at this stage — just like in cancer or HIV — is attack the disease from many angles."
On their end, Cohen and Klee have said they expect they'll need to study their drug in a broader pool of ALS patients, in part because doctors and insurers are going to want that information. It's unclear whether such studies will take place — or be required — before the AMX0035 can be filed for approval.
Paganoni anticipates that, should Amylyx's drug come to market, it will be used in combination with the currently available treatment options.