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Nancy Frates had just finished attending the annual ALS Ice Bucket Challenge outside the dorm named for her son, Pete Frates, at Endicott College on Sept. 29 when she got a text.
It was a message she’d been waiting for: Relyvrio, a drug developed to treat amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig’s Disease, had won approval from the FDA, making it the third treatment approved in the U.S. for tackling the fatal illness.
The night before, Frates and her family attended the Bourque Family Foundation Captain’s Ball, an event organized by former Boston Bruins captain Ray Bourque, at T.D. Garden. The gala was held to honor and remember the life of Pete Frates, who died in December 2019 at the age of 34.
Diagnosed with ALS in 2012 at the age of 27, Pete Frates propelled the disease into the public consciousness in 2014 after he was nominated to perform the Ice Bucket Challenge. The former captain of the Boston College baseball team tapped into the vast Boston sports community and the challenge quickly exploded, spreading across Boston and the rest of the world with entire cities, celebrities, tech moguls, and former presidents filming themselves getting doused with ice water to raise awareness and funds for ALS.
More than 17 million videos related to the challenge were shared on Facebook and watched by more than 440 million people, over 10 billion times. The campaign has been credited with raising over $225 million worldwide.
Among those who received funding from the windfall raised by the Ice Bucket Challenge were recent graduates of Brown University, Josh Cohen and Justin Klee. They’d started a company together in 2013 — Amylyx Pharmaceuticals — focused on developing treatments for degenerative neurological disorders like ALS. In 2016, their Cambridge-based company was awarded $2.2 million in grant funding from the ALS Association, raised through the 2014 Ice Bucket Challenge, for the development and trial of AMX0035 — the drug that eventually was renamed Relyvrio and approved for use by the FDA in September.
With staff from Amylyx at the gala in honor of her son, Frates said all talk was focused on sending prayers for the FDA’s vote the next day.
She and her family had high hopes for the treatment.
“You can understand our emotions were very, very high,” she said of finally getting the text about the news.
Since then, Frates and her family have been talking with the ALS patients and their families who they mentor, ensuring everyone has their paperwork ready for when the treatment will be distributed — likely by Thanksgiving.
“It’s a big step,” Frates said. “A big step.”
Dr. Sabrina Paganoni, co-director of the Massachusetts General Hospital Neurological Clinical Research Institute and a physician scientist at the Healey Center for ALS, was one of the principal investigators for the trial of Relyvrio.
She called the drug’s approval a “fantastic milestone” in the ongoing work to address ALS, which affects nerve cells in the brain and spinal cord, causing loss of muscle control starting with twitching or limb weakness and progressing to loss of the ability to control the muscles needed to move, speak, eat, and breathe.
“The entire community is really excited about this approval. … This really provides another tool for our patients to help fight the disease,” she said. “So this is really welcome news.”
Relyvrio is a combination of two drugs that each target a different component of the cell, Paganoni said. The idea is that by combining the two drugs there is maximum impact on the progression of the disease.
For the trial, she and her colleagues compared ALS patients who were randomly assigned Relyvrio, or AMX0035, to those who received a placebo.
What they saw was that those who received the new treatment retained their functional independence for longer for a number of activities, including walking, swallowing, breathing, handwriting, and being able to feed themselves.
“They retained their functions longer and also they lived longer,” Paganoni said.
Using the most conservative analysis, the doctor said people taking the drug were found to live five months longer than those not on the treatment.
But she said another, newer analysis made in comparison to natural history studies suggests the actual benefit may be much longer — more like 10 months.
Addressing concerns that were raised during the approval process for Relyvrio that the study was not large enough and did not produce convincing-enough results, both Paganoni and Frates said it was the data, not advocacy from the ALS community, that convinced regulators to ultimately approve the drug.
“This drug was approved based on one Phase 2 clinical trial,” the doctor said. “Normally the FDA requires a second trial for approval. And in fact, a second trial, a large global Phase 3 study is already ongoing. However, for U.S. patients, the FDA approved the drug based on one trial because of the robustness of the data from that one trial, in conjunction with the huge, unmet need for ALS.”
Frates pointed to the “horrifying journey” a diagnosis of ALS takes a patient and their family on.
“Let’s be perfectly clear, when you’re given a diagnosis and a prognosis of two to five years to live, can you wait around?” she said. “If it’s showing progress, all I ask is every single person to think about this — if your loved one was living with ALS right now, would you say, ‘No, we’re going to wait two to three years for a larger sample size?’ Absolutely not. And the FDA said the same thing.”
The potential of slowing the progression of the disease for 10 months could amount to another year for a patient, she said.
And that, she stressed, is not nothing to a patient and their families.
“What happens in that year, that 10 months? Well, all the milestones that my son missed,” she said. “If he had an extra 10 months to a year, another birthday, another Christmas with [his daughter] Lucy. His brother got engaged who had taken care of him for seven years. He would have seen all that.
“But you know what else, he could be around for another building block to be approved, because we have so many drugs in the pipeline right now,” she added.
One year could actually end up being another four years if more treatments were to come online, Frates argued.
Relyvrio can be taken alongside the two previously approved ALS treatments, which target other aspects of the disease.
“We now give as many tools as possible to our patients to be able to fight the disease,” Paganoni said. “And again, even this combination of three drugs is not a cure. There’s still a lot to do to completely stop ALS. But certainly this is a step in the right direction.”
The current thinking is that a “cocktail” of drugs is the best approach to treating a complex disease like ALS. That’s the approach that was used for HIV, which is now considered a manageable, chronic health issue rather than a fatal condition.
It’s a path that both Paganoni and Frates said they hope to see for ALS.
“It’s a great analogy,” Paganoni said. “The first few drugs that were approved for HIV were not curative. People would still progress; however, in combination with more and more drugs — and thanks to advocacy and continued research — it actually is now, fortunately, a chronic disease.
“And so I think that again, hopefully this is just the first of many more that we can continue to add to the toolbox,” she continued.
If ALS can be made into a liveable disease, Frates said the entire community would take that milestone and press on.
“Then we’ll go for a cure, and then we’ll go for reversal,” she said. “Those are long-term goals, but right now we’re building towards living longer, meaning being around for more things that are coming.”
The impact and role of the Ice Bucket Challenge in spurring the progress being made toward treatments for ALS is undeniable.
Compared to just five years ago, Paganoni said the landscape is “completely different.”
“There’s been a lot more interest in ALS and more investment in ALS,” she said. “So essentially right now there is a lot of hope on the horizon because there are many more drugs that have been tested. We have a very collaborative academic community, we have a very engaged patient community, and lots of companies in the space that are excited to be developing drugs for ALS.”
Asked if she and her family ever imagined back in 2014 that the Ice Bucket Challenge would result in a new treatment, Frates was quick and emphatic in her answer.
Yes, they did.
“We knew it was going to happen because we knew what the status of the space was prior to the Ice Bucket Challenge,” she said. “Remember, Pete was diagnosed in 2012. So in 2012, there was nothing. All the researchers and scientists were operating in silos because it was such an unknown and underfunded disease.”
Her son knew that trajectory had to be changed in order to alter the stagnant nature of the space.
Scientists, she said, were spending too much time trying to get what little funding was coming into the space.
“We were like, ‘Well, wait a minute, if there’s no money coming in, then the people who are trying to find a treatment or cure for this thing are also fighting for the same few dollars,’” Frates said. “So that’s why our focus was on marketing the disease. We knew we had to tell the story of the disease for people to really realize it.”
When the Ice Bucket Challenge resulted in raising $115 million for the ALS Association in one month, Frates said she and her family knew the treatments would follow.
The Frates family, she pointed out, hasn’t just been connected to the newest treatment through the funding delivered in 2016.
Her husband’s cousin, James Frates, who over the years participated in all the family’s advocacy and had worked in pharma for years, took a job three years ago at Amylyx as chief financial officer.
Frates said when she heard he’d taken the job, she cried for three days.
It added another family connection to the promising treatment — this time, with a Frates helping get the money to bring the treatment to market.
“We were involved in the beginning of it, and at the end of it,” she said of Relyvrio’s path to patients.
Asked how she believes Pete would have reacted to the approval of the drug, Frates said her son would have raised a pint and cheered.
But then the next day, he would be back at work, planning for the next step. The next milestone.
“Pete knew he was chosen for this,” Frates said. “He wasn’t OK with being diagnosed with ALS, but how he knew in his soul that everything he had done in life had brought him to a point that God chose him for this.”
He’d always been a servant leader, always the team captain. He was the go-to guy, she said, for all his coaches, teachers, and mentors when they wanted to get something done, knowing that Pete would lead with kindness and by example.
“He was a visionary,” Frates said. “Pete said the night he was diagnosed that we were going to change the trajectory of this disease. Now, he didn’t know in what form that was going to take. But he knew that we were going to get to work, and he knew that’s what we were going to do.”
The way he approached raising awareness and funds for ALS can be a model for others seeking change on other causes, Frates said.
Just start by telling your story, she urged.
“When you’re given a challenge like [ALS], it’s about what can be done so that nobody else has to face the challenge,” she said. “And for Pete it was look, ‘I’m a Division 1 athlete, I’m in great shape, I’m 27 years old, and this is going to be a visual journey. This is going to be visual, and I’m going to show people no matter what happens to me.’ People are going to see what’s going to happen. Because that is the story. And if you tell the story, people will open their hearts to you.”
It was his determination and his leadership that inspired everyone around him; a legacy that continues to make waves after his passing.
Knowing that the Ice Bucket Challenge was that trajectory change that her son envisioned is what Frates said helps her get up and smile “every day.”
“People have to remember, I don’t have Pete anymore,” she said. “It will be almost three years that I don’t have him anymore. But his inspiration is what keeps us going every single day.”
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