David Frei, 54, has been struggling with time. Some things he wants to slow down, others he wants to speed up.
He can’t keep up with trying to adapt to the paralysis that started in his legs and is creeping up his body. Every solution is temporary.
“It takes a week to notice a difference,” he says. “I think, ‘Oh, the week before I could do this better.’”
What he wants to speed up is the release of more information about a new drug to treat his fatal ALS, also called Lou Gehrig’s disease, which will eventually take his ability to breathe.
The drug edaravone, under the brand name Radicava, was lauded as a minor miracle when it was approved in the U.S. in May 2017. It was the first new medication in 22 years to help treat the neurodegenerative disease. It has also been approved in Japan and South Korea.
Questions by some doctors, patients and advocates have come faster than answers, however.
The Post-Dispatch wrote about Frei when he started the taking the drug in November 2017. After a year of receiving the infusions 10 out of every 28 days, Frei took half the doses in November and December before deciding to quit.
He admits he didn’t really have much to base his decision on. He seemed more fatigued during the infusions, felt more muscle twitching. As his legs lost all strength, his core weakened and then his arms, he kept wondering, was he progressing faster?
Frei searched the stories posted in a Facebook group of other ALS patients taking the drug, which ranged from feeling the drug was dramatically slowing progress to it making symptoms worse. He talked to his doctor. He wrote Mitsubishi Tanabe Pharma America, which makes the drug. He looked for more research.
Despite the drugmaker announcing that more than 3,500 patients have been treated with Radicava in the U.S., there’s been no new information since a small study in Japan on its effectiveness.
“I’m not saying it doesn’t work,” Frei said. “I’m saying you just don’t know.”
Frei has always been skeptical.
The only positive study of the drug involved a small subset — 137 Japanese patients who were within two years of diagnosis in early stages of the disease and rapidly progressing. They were studied for only six months. Company officials argue the design was necessary in order to more quickly determine the drug’s impact. The results were modest — the drug slowed progression of the disease by a third.
Company officials argue the limited study design was necessary to more quickly determine the drug’s impact.
The drug was approved by the FDA for all patients in every stage of ALS. About 6,000 Americans are diagnosed with ALS each year, and 20,000 are living with it any given time.
Frei was able to receive his monthly stretch of infusions at home, a process that took about 75 minutes.
But he worried about the frequent intrusion. Was that how he wanted to spend his time? Would it ruin his time?
Time has always been a constant factor in the back of Frei’s mind. He’s always weighing the best use of it.
Frei pondered this struggle in one of his posts on a blog he’s kept since getting diagnosed in October 2016. Most people with ALS die within two to five years of diagnosis.
He would rush to get through the mundane and tedious in life; struggle with how to best spend free time; and felt he had to be as efficient as possible at everything. An elite athlete and lifelong daredevil, he often pushed himself to go faster.
“All my life,” Frei wrote, “I have had a tendency to be afflicted with this sense of regret that I really should be doing something else.”
He’s realized the moments when he is most happy, however, are when he loses the concept of time. Or stops caring about it.
When he wrote the post last fall, those moments were often when he was outside on a beautiful day with his wife, Mary Piper, on his “glorified high-speed electric wheelchair” that is his recumbent tricycle.
“It appears like this is something that I can not force or plan,” he wrote last fall, “it must just happen.”
Patient’s needs, goals
After Frei decided to stop the drug, doubt crept in. He turned a corner. He could no longer move in and out of a chair on his own. He and his wife hired a caretaker for the first time to help while she was gone. They began looking at patient lifts.
Frei even called his insurance company to see whether the cost would be covered if he decided to start the infusions again.
“My insecure human who has doubt is saying maybe I shouldn’t have quit,” he said, “but the scientific part of me is saying if you were iffy before, you definitely should be iffy now.”
Soon after the drug was approved in the U.S., a network of ALS treatment centers in Europe agreed that questions remain. The group called for a clinical trial that would study the drug for at least a year and include survival data.
A year ago two researchers — Dr. Crystal Yeo from Houston Medical Hospital and Dr. Zachary Simmons from Pennsylvania State University — published an article warning that initial reports about the drug may be overly enthusiastic and misleading, especially to a population desperate to try a treatment.
Yeo and Simmons urged ethical discussions with patients that balance hope with science: explain the limited and modest benefits, intense treatment schedule, the cost (about $140,000 a year, not always fully covered by insurance) and side effects, such as a risk of infection and blood clots from the intravenous port.
Discussions should also take into account a patient’s quality-of-life goal, which isn’t always linked to physical function and strength but to mindset and interactions, they wrote: “A physician who takes the time to understand the clinical trials that lead to drug approval, and who can compassionately frame the medical facts in the context of the patient’s needs and goals, is an invaluable resource to patients.”
Six months later, Dr. John Turnbull from McMaster University in Ontario, Canada, published an article arguing that infusions of edaravone may even be harmful. All the patients in the Japanese study received an infusion of either the drug or a placebo. But both groups, he wrote, “likely did worse than no intervention.”
It all leaves Frei wondering.
“It’s that middle area. Is it helping? Is it hurting? Do I take it? Do I not take it?” he said. “You just keep coming up against that wall of no knowledge and frustration.”
Frei also hates costing the health care system more than $140,000 a year on something marginal.
“I have never been a leech in my life. I feel like it’s not doing much good when I’m costing way more than I’ve ever made in my life,” he said, “and it’s costing other people.”
In their best interest
MT Pharma paid a total of $241,000 to neurologists last year for things such as consulting services and educational events, according to the online Open Payments Data maintained by the Centers for Medicare and Medicaid Services.
One of the top two paid doctors in the country, Dr. Jonathan Katz, director of an ALS treatment center in San Francisco, was quoted in a company news release about FDA approval and other news reports about Radicava.
Katz called the drug “incredibly significant” and an “uplifting milestone” that “brings us into a new era of treatment.” He received nearly $25,000 in 2017 — nearly half of the total amount he received from all drug companies, according to the site. Nationwide, neurologists receive an average of $9,000 from drugmakers.
The ninth-highest paid doctor is in St. Louis. Dr. Ghazala Hayat, a neurologist at the SLUCare ALS Clinic, received nearly $7,000 from MT Pharma last year. She said in an email the payments were for educational presentations to health care providers about the “pivotal trial results and FDA-approved parameters and guidelines for the use of” Radicava.
Hayat is quoted in a SLUCare advertorial that appears on stltoday.com promoting its ALS clinic and Radicava: “It’s a treatment, not a cure, but this is slowing down the process so you’re able to do more things. Your quality of life is better.”
Hayat said she has continued to receive payments this year from MT Pharma for speaking engagements and for participation in an educational video.
The relationship does not affect discussions with patients, she said. “My only consideration in talking with patients is what is in their best interest in terms of treatment options and quality of life. I let patients know of the risks and benefits, and they decide what they want to do. Patients bring their values and concerns to the conversation. I provide honest answers to their questions.”
The only other St. Louis area doctor receiving over $1,000 from the drugmaker in 2017 was BJC HealthCare’s Dr. Robert Bucelli. He received almost $3,700 for travel to Dallas, which he says was for serving on one of several advisory boards created by MT Pharma to get input from providers. “The payment has not influenced my approach to educating patients about the drug, including its side effects,” Bucelli wrote in an email.
Hayat said she tells her patients taking Radicava that ALS can vary in how quickly it progresses in each person, so a 33 percent slower decline is hard to detect. Yet a few months later, they complain the drug is not doing anything.
“There’s no way a patient will know if it’s helping him or not,” she said. Same for physicians.
Hayat said a consortium of ALS clinics across the country is collecting information on patients taking Radicava, and “hopefully soon there will be more and more data that will tell us how patients are doing.”
Dr. Timothy Miller, a lead ALS researcher at Washington University School of Medicine, said it may be difficult to get meaningful information from anything other than a clinical trial, which requires placebo and control groups as well as matching similar patients.
“It is going to be challenging to tell a small or medium effect of Radicava,” he said. “That is hard to see.”
Heather Burns works as a care manager for the ALS Association St. Louis Regional Chapter, which provides education and support services in more than 100 counties in Missouri and Illinois. She said families and advocates are frustrated.
“We don’t have as much information as we should,” she said. “There are some who don’t care about lack of information. They want to try it, because they don’t have any other options, but there are also people who do want information, and they deserve that.”
MT Pharma has announced it has a six-month clinical trial starting this spring that will study 200 people taking Radicava. Washington University is one of the study sites. The study is open to anyone whose infusions are covered by insurance; company officials say about 80 percent of patients are covered.
The study will measure biomarkers for ALS — including oxidative stress, inflammation, neuronal injury and muscle injury — in an effort to better understand disease progression and effect of the drug.
Progression of ALS is currently measured in physical functional assessments, which can vary among providers.
But all of that takes time, which Frei doesn’t have.
“What I want is for all the doctors and the drug companies to get together in a more timely fashion with data on whether it’s working or not,” he said.
Frei has decided to stop wringing his hands over it. He’s done talking about it, wondering about it, rehashing “mediocre information” over again, he said. Being on the fence is a tiresome place to be.
“It’s more enjoyable to not have that turmoil,” Frei said as the sun went down and he waited for his wife to get home to have dinner.
He’s realized that whatever he is doing is fine. “Some,” he said, “are always thinking there’s something better they can be doing with their time.”
Janelle O’Dea of the Post-Dispatch contributed to this report.