FDA approves first ALS drug in 5 years after pleas from patients

On Thursday, the Food and Drug Administration overcame the doubts of agency scientists and approved a hotly debated drug for ALS, a decision that encouraged patients and advocates who pushed for drugs, but has raised concerns among some experts about whether treatments for extreme conditions receive sufficient scrutiny.

“It’s a huge deal,” said sunny bush, 35, who was diagnosed with ALS seven years ago after struggling to close his left glove while playing softball. She plans to start taking the medication as soon as she can.

“Anything that shows some efficacy is important,” the Pico, Texas resident added. Even a small change, Brous said, “could mean the difference between signing my own name and someone else signing it for me.”

The newly approved therapy, which will be sold under the brand name Relyvrio, is designed to slow the disease by protecting nerve cells in the brain and spinal cord destroyed by ALS – amyotrophic lateral sclerosis. The disease paralyzes patients, robbing them of their ability to walk, talk and possibly breathe. Patients typically die within three to five years, although some live much longer with the condition sometimes called “Lou Gehrig’s disease” for the famous baseball player diagnosed in 1939.

“This approval provides another important treatment option for ALS, a life-threatening disease that currently has no cure,” Billy Dunn, director of the FDA’s Office of Neuroscience, said in a statement.

The agency said Relyvrio’s effectiveness was demonstrated in a 24-week study in which 137 patients were randomized to receive Relyvrio or a placebo. Patients treated with the drug experienced a 25% slower rate of decline in performing essential activities such as walking, talking and cutting food compared to those receiving a placebo.

Additionally, according to the FDA, a long-term analysis showed that patients who initially received Relyvrio compared to those who took the placebo lived longer. Amylyx, the Cambridge, Mass.-based biotech company that makes the drug, said the survival benefit averaged about 10 months.

During reviews of the drug, FDA staff expressed concerns about the drug’s effectiveness and asked questions about the clinical trial. Thursday, the agency recognized there were “limits” to the data that led to uncertainty about how effective the drug was. But the agency said regulatory flexibility was acceptable because of the “severe and life-threatening nature of ALS and the substantial unmet need” for treatments.

Amylyx officials said they plan to move as quickly as possible to make the drug available.

“Amylyx’s goal is for everyone who is eligible for Relyvrio to have access to it as quickly and efficiently as possible, because we know that people with ALS and their families don’t have time to wait,” the authors said. co-chief executives Josh Cohen and Justin Klee in a statement.

The company said pricing information would be available soon.

ALS patients, advocates and specialists hailed what they called a landmark endorsement, saying the drug represents the kind of modest advancement needed to make progress against the disease. About 30,000 people in the United States have ALS, with 6,000 new cases diagnosed each year. Two other drugs are approved for the disease but have extremely limited effectiveness.

However, some drug policy experts have said there is not enough evidence that the drug works. A trial with 600 patients will not be completed until late 2023 or early 2024.

“There is evidence to support the efficacy of the product, but I don’t think it meets the bar that the FDA typically requires,” said G. Caleb Alexander, internist and epidemiologist at Johns Hopkins Bloomberg School. of Public Health who sits on the FDA advisory committee that reviewed the drug. “How much should the FDA lower the bar – if at all – for products against a devastating disease” that lacks effective treatments?

Diana Zuckerman, president of the National Center for Health Research, a think tank, agreed.

“How many ineffective ALS drugs do we need?” Zuckerman said. “It would be better to have one that has been proven to make a significant difference to living longer.”

But Jinsy A. Andrews, associate professor of neurology and director of neuromuscular clinical trials at Columbia University, applauded the approval and said she plans to start prescribing the drug as soon as it becomes available. Other ALS specialists agreed.

“I see patients living with this disease and diagnose them every day,” Andrews said. “So having another therapy for the toolkit is helpful.” Andrews is a researcher in the large drug trial currently underway.

The drug, the first new approved treatment for ALS in five years, consists of two components: a prescription drug called sodium phenylbutyrate used to treat rare liver disorders and a nutritional supplement called taurursodiol. The medicine comes in a powder form that dissolves in water and can be swallowed or given through a feeding tube.

Two Brown University undergraduates – Cohen and Klee – has come with the idea of ​​the therapy nearly a decade ago, initially thinking it would be for Alzheimer’s disease.

ALS advocates said the approval shows the importance of patients and advocates getting involved in efforts to bring the drugs to market.

“We still have a lot of work to do to cure ALS, but this new treatment is an important step in that fight,” said Calaneet Balas, president and CEO of the ALS Association.

In 2014, the organization raised $115 million in six weeks through the Ice Bucket Challenge and provided $2.2 million to help pay for testing AMX0035, the name of the drug during development. The drug is the first funded by the organization to receive FDA approval. Amylyx has agreed to use the proceeds from the sale of the drug to repay the organization 150% of its investment.

In 2019, Obama White House staffer Brian Wallach and his wife founded a group named I AM ALS after Wallach’s diagnosis. This organization has made the marketing of the drug Amylyx a priority.

Both groups have urged the FDA to be faster and more flexible in approving ALS drugs, saying patients will accept treatments with increased safety risks in exchange for even a small benefit — one point. of view embedded in the agency’s 2019 guidelines to the pharmaceutical industry. industry on the development of therapies for ALS. In 2020, the two ALS organizations submitted over 50,000 signatures to the FDA calling for approval of AMX0035.

In a do-it-yourself effort, some ALS patients in the United States are already taking the drug’s ingredients. Since sodium phenylbutyrate was already approved, doctors can prescribe it off-label to patients with ALS. The dietary supplement taurursodiol, also known as TUDCA, can be purchased online.

Steve Kowalski, 58, who lives in Boston and takes the drug’s components, along with the other two drugs approved for ALS, credits the diet with slowing his deterioration. With careful planning and the help of his three adult children, he can still go see his beloved Red Sox, but he’s exhausted when he gets home, he said.

Kowalski praised the FDA’s action on the drug. He would rather get an approved, high-quality version of the drug than have to buy a supplement online.

The company’s application to the FDA was based largely on the only 24-week clinical trial and follow-up data from an “open label” study in which all trial participants were offered the drug.

Typically, the FDA expects drugmakers to submit “substantial evidence of effectiveness” provided by two well-designed clinical investigations. But the agency says a single trial may be sufficient if the study demonstrates a “clinically significant and statistically highly persuasive effect” on prolonging survival or some other aspect of the disease.

In March, however, FDA staff issued a mostly negative opinion. Evaluation — suggesting the data was unconvincing — and agency advisers agreed, voting 6-4 to recommend against FDA approval. Patients and attorneys flooded the FDA with more than 10,000 emails asking for approval, the attorneys said.

In a rare move, the FDA held a second advisory meeting this month to review additional analyzes submitted by the company. Again, FDA staff suggested in a note that there was not enough evidence of effectiveness to approve the drug.

But the tone of the meeting was different significantly from that of the first session. At beginning, Dunn acknowledged that the data on the drug raised many questions, but also pointed to the “huge unmet medical need” for ALS and the severity of the disease. He said the agency had the legal authority to be flexible. And in a highly unusual move, Dunn asked Amylyx officials if they would voluntarily pull the drug from the market if the big trial failed; they said they would.

While some of the external experts on the advisory board have changed positions, the group recommended approval 7-2.

The drug debate echoes the battle over Aduhelm, the controversial Alzheimer’s drug approved by the agency in June 2021. Critics said there was little evidence of effectiveness for the drug, and Medicare refused to cover it except in trials. The drug collapsed on the market, never gain traction with patients or doctors.

But ALS doctors insist the ALS drug is different. It achieved its primary goal in the trial, although the benefit was modest, they noted. And even small gains are meaningful for people with the disease, they argued.

The FDA said the drug had no major safety concerns; the most common side effects were diarrhoea, abdominal pain, nausea and upper respiratory tract infections. The agency added that the bile acid taurursodiol can make diarrhea worse in patients with conditions that interfere with the flow of bile acids and urged such people to speak to a specialist before taking the treatment.

Canada recently approved AMX0035 on a conditional basis. Amylyx can sell the drug there, as long as the benefits of the treatment are confirmed by the larger trial.

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