Opinion: As a pediatric cancer researcher, I admired the FDA. Then I got ALS

Amyotrophic lateral sclerosis (ALS), as I have unfortunately come to learn, is a terrible disease with no cure. Some exciting treatments are on the horizon, but the Food and Drug Administration’s Office of Neuroscience, which has the task of overseeing the development of new ALS drugs in the U.S., has repeatedly failed to take aggressive steps to greenlight these experimental therapies. I, and others like me, desperately need the FDA’s neuroscience office to be more aggressive in approving experimental treatments.

That might sound like wishful thinking. Or it might sound like naivete on the part of someone who does not understand the rigors of the drug approval process. But I know from my work as a childhood cancer specialist for the past 45 years that the agency is capable of doing better.

I have taken care of kids with cancer and conducted clinical trials with the aim of improving the cure rate of childhood cancer, such as leukemia. Most of these trials involved novel treatments or approaches.


Over the course of my career, the FDA has radically reshaped its approach to cancer drugs, and the results have been spectacular.

Since the 1960s, researchers have been able to move the cure rate of all childhood cancers from 25% to 80%. The engine for this was randomized clinical trials, all supported by the National Cancer Institute, involving children with cancer, with permission from them and/or their parents.


With most of these trials, we did not wait for confirmation from additional trials to move forward. As long as one arm of a trial appeared to offer superior results compared to the standard of care, it quickly became the new standard. Effective molecular inhibitors, immunologic stimulators, and other agents were developed, some with only small trials showing some efficacy in adult cancers, and tested in children. The FDA granted many of these drugs accelerated approval to get them to patients faster, when there were no better alternatives.

The FDA’s Oncology Center of Excellence has been run for the past decade by former practicing oncologists with extensive clinical trial expertise. To their credit — and to the benefit of thousands of children and adults — the approval of novel agents has been greatly accelerated, with the advantages outweighing risks.

To be sure, the standards the FDA applies to serious childhood and adult cancers would not be acceptable for less-serious diseases. The point of a treatment is to make one better off than before. But when a diagnosis is life-threatening, risks need to be taken.

I was diagnosed with ALS in December 2019. After learning that the few drugs on the market offered a couple months of benefit, I dove into the literature to see what treatments were on the horizon.

One example of a promising new agent is a two-drug oral combination called AMX0035. It showed an impressive slowing of loss of muscle function using a widely used validated assay, in a recent well-run, randomized, placebo-controlled trial published in the New England Journal of Medicine. Life-threatening side effects: none; other side effects: temporary diarrhea. In a recent follow-up, published in the journal Muscle and Nerve, AMX0035 significantly improved survival by 10 to 18 months.

If AMX0035 was a new cancer drug, with approval sometimes being granted with just the promise of a three-month survival advantage, this would be a home run. Yet instead of approving the drug and making it available to all Americans with ALS, the FDA is requiring Amylyx, the company that makes the drug, to conduct a larger Phase 3 trial. It will take at least three years to accrue participants, conduct the trial, present the results, and have the FDA conduct its analyses.

To wait for those results could lead to significant avoidable decline in function — and death — for the 15,000 or so Americans with ALS, and the 5,000 who will be newly diagnosed with it each year. Most of us would choose to take AMX0035, even if potential serious side effects are ultimately discovered. Those who do not want the drug do not have to get it, of course. But many of us will line up for it, with excitement. (Everyone has their own personal risk-reward calculus, but I’ll happily trade a little diarrhea for another year of life.)

In June, Health Canada, that country’s equivalent of the FDA, approved AMX0035, now named Albrioza. The company has also asked the European Union to approve the drug.

Why should a drug conceived by two undergrads at Brown University, tested in an animal model at Harvard, and followed by a successful human trial that the New England Journal of Medicine saw fit to publish — in other words, a drug developed entirely in the U.S. — be approved for use in Canada and the EU before being approved here?

The FDA’s Office of Neuroscience has called another meeting of its advisory committee, set for September, once again delaying decisions about AMX0035. It is possible the office is being overly cautious because of the firestorm surrounding its approval of Aduhelm to treat Alzheimer’s disease, with ALS patients caught in the crossfire.

In a review of FDA centers’ use of the accelerated approval process between July 2008 and December 2017, two-thirds of drugs approved this way were for cancer, and just one represented treatment for a neurologic/muscular disorder. I find that shocking!

It is worth noting that the Office of Neuroscience approves all drugs at a slower rate than the FDA’s Oncology Center of Excellence, regardless of the process, with a similar number of personnel.

The Office of Neuroscience needs to increase access to novel agents for people with life-threatening diseases like ALS. All they need to do is talk to their colleagues down the hall to borrow the approach used for cancer drugs.

William G. Woods is a pediatric oncologist and the former director of the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta and chief of pediatric hematology, oncology, and bone marrow transplantation at Emory University in Atlanta.

Source: STAT