Of all the ways the body can go wrong, A.L.S. is one of the most frightening. It begins subtly — a twitching muscle, a cough when you swallow or a clumsy hand. But then it progresses. Motor neurons degenerate and die. You lose the ability to talk, to eat and ultimately to breathe. There is no cure. Treatment will slow progression somewhat, but not enough.
A diagnosis of A.L.S., or amyotrophic lateral sclerosis, begins a race against the clock. What do you do to make yourself heard before you are rendered voiceless? How do you find a trial or a treatment to extend time long enough to be there for the next scientific advance?
I rarely have time to probe the answers to these questions when I take care of people with A.L.S. in the intensive care unit or long-term hospital ward. But the faces stay with me. I remember a woman who just wanted to go to the beach once more, to eat a lobster roll before she could no longer swallow. I remember a young man with an elaborate sound system in his hospital room whose wife had left him; there was no one to take care of him at home, and so he would live out his days in a nursing facility.
In contrast to the experience of those with cancer, for whom there is often the promise of a new drug around the bend, there are relatively few therapies for A.L.S. Perhaps that is why I became so interested recently in the vigorous debate over the possible approval by the Food and Drug Administration of a new treatment for A.L.S.: a stem cell therapy called NurOwn developed by BrainStorm Cell Therapeutics. Some patients who had early access to the drug described improvement like being able to pick up a remote control for the first time in months or being able to walk through the grass.
But the data did not bear out these experiences. Ultimately, the F.D.A. advisory committee that evaluated NurOwn recommended against approving the therapy, a decision that devastated many A.L.S. patients and their family members.
This is the latest in a sequence of controversial drug approval decisions from Alzheimer’s to muscular dystrophy that see educated and impassioned patient advocates pleading their case before regulatory authorities. These debates extend beyond the quality of scientific evidence. The decision of whether to approve a drug for a lethal disease gets to complex, deeply human questions. How far do you go when the alternative is certain death? What level of proof is good enough, and who gets to decide? And when someone is facing a terminal illness, what is the cost and benefit of hope, even hope for an outcome that might never be realized?
A few years ago, I began to follow a man named Brian Wallach on social media. It was some time after his A.L.S. diagnosis in 2017, back when his voice was still audible and he could ride his Peloton stationary bicycle. He was around my age, in his late 30s at the time, with a wife and two young daughters. He described his disease, somewhat hopefully, as “currently fatal.”
After all, when he was diagnosed — on the day his newborn daughter came home from the hospital — a new drug for A.L.S. had recently been approved. Surely there were more in the pipeline. The first neurologist he saw had told him that he would be dead in six months, and that he should go home and eat whatever he wanted and be with his family. But the specialists he went on to see pointed him in the direction of clinical trials.
Mr. Wallach knew that A.L.S. is a terminal illness. That knowledge was with him every moment of every day. But if there was a hope for a different outcome, he wanted to grab hold of it. So Mr. Wallach and his wife, Sandra Abrevaya, researched the existing data for drugs that had been proven safe and had some evidence of benefit. They knew that no one drug would offer a magic bullet. But perhaps in combination, the available treatments could help slow the progression of Mr. Wallach’s A.L.S. enough so that he would still be alive when the next drug became available. There was no time to wait.
They drew on their skills and connections — Mr. Wallach is a lawyer while Ms. Abrevaya has headed nonprofit organizations, and both worked in the Obama White House — to build what has been described as the most successful patient advocacy campaign in decades. They catalyzed new research, helped pass a bill to allocate millions in federal money to A.L.S. studies and improved access to promising investigational drugs for patients who are not eligible for clinical trials. (The nonprofit that Mr. Wallach and Ms. Abrevaya founded, I AM ALS, provided a $100,000 grant to BrainStorm for its research into NurOwn.) Mr. Wallach would be among the first generation to survive A.L.S., he wrote on the social media platform X.
I want to believe this. Though he is nearly completely paralyzed and his voice is so weak that his wife serves as his translator, he is alive six years after his diagnosis, still breathing on his own. That itself is remarkable.
And yet as doctors — particularly those of us working in places like the I.C.U. — we are trained to tread cautiously when it comes to hope. We applaud families for being “realistic,” which generally means that they do not ask for outcomes we consider to be impossible. We guard carefully against what we think of as false hope or hope for an outcome that we believe cannot come to pass. If hope — even false hope — is a kind of medicine, it is not one that we are comfortable with.
That said, maybe hope despite long odds is not always the worst thing, especially when the alternative is no hope at all. For many A.L.S. patients, that is what NurOwn represented. According to BrainStorm, the treatment involves stem cells harvested from patients’ bone marrow and engineered in a lab to prevent nerve damage and cell death associated with A.L.S. Those cells are then given back to the patients through injections into the spine. The science was exciting, the early data promising.
But the data from the company’s largest trial, enrolling nearly 200 patients, were negative — the treatment was no better than placebo in the full patient population. Further analyses suggested those with a milder form of A.L.S. may benefit, but the subgroup population was small and these improvements fell short of consistently meeting the bar of statistical significance.
Patients offered impassioned testimony, describing how NurOwn had given them back a bit of their autonomy and stilled the relentless pace of this disease. The drug would not work for everyone. But for patients facing certain death, the idea that it might help some of them was enough, even if that had not been borne out in a rigorous scientific study.
Unconvinced, and despite the F.D.A.’s promise to be more flexible when it comes to approving drugs for fatal diseases, the advisory committee nearly unanimously voted against recommending NurOwn for approval. I can’t know if that was the right decision. Maybe a larger trial would have proven NurOwn to be beneficial and maybe not. BrainStorm is now working with the F.D.A. to design another trial. But for patients whose disease is rapidly progressing, now, those results might come too late.
There is a narrative that desperate patients would try anything, and the role of the F.D.A. and the health care system more broadly is to protect those patients against themselves. That is flawed. Mr. Wallach and Ms. Abrevaya are indeed desperate. Their lives have been ravaged by this disease. But their judgment is still intact. Their decisions are not influenced by the nihilism that comes from despair. They simply want the ability to decide for themselves whether to take drugs that might be helpful.
Of course, no one wants the F.D.A. to approve drugs that are useless or, worse still, dangerous. And the F.D.A. has made decisions in recent years that demonstrate a willingness to make available drugs for lethal diseases based on imperfect data, most controversially with the Alzheimer’s drug Aduhelm, but also with other A.L.S. treatments. But where does this flexibility end? Where do we draw that line?
One worry is that increasing flexibility will mean the F.D.A. is influenced by the loudest voices to put drugs on the market that are expensive and possibly ineffective. But isn’t it also dangerous, maybe more so, to be wrong in the other direction — to withhold a drug that might actually be beneficial, when the alternative is certain death? “The treatments may not cure us, but they have a chance to help us,” Mr. Wallach said. “And that chance is everything, when you know what is behind door number two.”
I thought of this conversation and of the NurOwn debate recently, as I walked through the long-term acute care hospital. I was taking care of a man in his 40s with a debilitating disease that had caused his muscles to shrink and atrophy, leaving him on the ventilator. From the bed, he mouthed to me that he was hoping to try to breathe on his own for at least part of the day. Looking at him, I was fairly sure that would be impossible.
I felt myself start to explain to him how unlikely that outcome was. Surely I should prepare him and guard him against false hope. But then I paused. The time might come for that. But for the moment, we would try.
Daniela Lamas is a contributing Opinion writer and a pulmonary and critical-care physician at Brigham and Women’s Hospital in Boston.
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