Pico, Tex. “Anything that shows any amount of efficacy is important,” the resident added. Even a small change, Brous said, “can be the difference between signing my name and someone else signing my name.”
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, making them unable to walk, talk and eventually breathe. Patients usually die within three to five years, although some live longer with the condition, sometimes called “Lou Gehrig’s disease,” after the famous baseball player was diagnosed in 1939.
“This approval provides another important treatment option for life-threatening ALS for which there is currently no cure,” said Billy Dunn, director of the FDA’s Bureau of Neurology.
The agency said the effectiveness of Relyvrio, the first new therapy approved for ALS in five years, 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 percent slower decline in performing important activities such as walking, talking, and eating compared to those who received a placebo.
In addition, the FDA said, long-term analyzes showed that patients who received Relyvrio versus those who initially received Relyvrio had better results. those who took a placebo lived longer. Amylyx, the Cambridge, Massachusetts biotech company that makes the drug, said the survival benefit averaged 10 months.
During the drug review, FDA staff raised concerns about the drug’s effectiveness and raised questions about the clinical trial. Thursday, the agency he admitted there were “limitations” to the data that resulted in uncertainty about the drug’s degree of effectiveness. But the agency said the regulatory flexibility was reasonable because of “the serious and life-threatening nature of ALS and the significant unmet need for treatment.”
Amylyx officials said they plan to move as quickly as possible to obtain the drug.
“[Amylyx’s] The goal is to ensure that everyone eligible for Relyvrio gets access as quickly and efficiently as possible because ALS patients and their families don’t have time to wait,” said co-CEOs Josh Cohen and Justin Klee.
The company said that information about the price will be provided soon.
Patients, advocates and ALS experts hailed what they called a landmark approval. said the drug is the kind of modest breakthrough needed to make progress against the disease. About 30,000 people in the United States have ALS, and 6,000 new cases are diagnosed each year. Two other drugs, including Radicava, which hit the U.S. market in 2017, are also approved for the disease, but with very limited efficacy.
Some drug policy experts say there is not enough evidence that the drug works. The 600-patient trial won’t be completed until late 2023 or early 2024.
“There is some evidence to support the efficacy of the product, but I don’t think it reaches the bar that the FDA typically requires,” said G. Caleb Alexander, an internist and epidemiologist at the Johns Hopkins Bloomberg School of Public Health. serves on an FDA advisory committee that reviews the drug. “How low should the FDA lower the bar for products for a devastating disease without 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 meaningful difference in living longer.”
But Jinsy A. Andrews, associate professor of neurology and director of neuromuscular clinical trials at Columbia University, welcomed the approval and said she plans to start prescribing the drug as soon as possible. Other ALS experts agreed.
“I see patients living with this disease and diagnose them every day,” Andrews said. “So it’s useful to have another treatment for the tool kit.” Andrews is currently an investigator in a large ongoing drug trial.
The drug consists of two components – a prescription drug called sodium phenylbutyrate, which is used to treat rare liver diseases, and a dietary supplement called taurursodiol. The drug comes as a water-soluble powder and can be swallowed or given through a feeding tube.
Two Brown University graduate students—Cohen and Klee— came With the idea of therapy about a decade ago, he originally thought it would be for Alzheimer’s disease.
ALS advocates said the approval shows the importance of involving patients and advocates in efforts to bring drugs to market.
“We still have a long way to go to cure ALS, but this new treatment is an important step in the fight,” said Calanet Balas, president and CEO of the ALS Association.
In 2014, the organization raised $115 million over six weeks through the Ice Bucket Challenge, with $2.2 million of that to help test the drug’s name, AMX0035, during development. The drug is the first organization-sponsored drug to receive FDA approval. Amylyx has agreed to use the proceeds from the sale of the drug to repay 150 percent of its investment in the organization.
In 2019, Obama White House staffer Brian Wallach and his wife started a group called I AM ALS after Wallach was diagnosed. This organization has made it a priority to bring Amylyx to the market.
The two groups have pushed the FDA to be faster and more flexible in clearing ALS drugs, saying patients will accept treatments with increased safety risks for even a small benefit — an idea included in the agency’s 2019 guidance on pharmaceuticals. to develop industrial ALS treatments. In 2020, two ALS organizations submitted more than 50,000 signatures to the FDA for approval of AMX0035.
In the United States, some ALS patients take the drug’s ingredients as a do-it-yourself effort. Because sodium phenylbutyrate is now approved, doctors can prescribe it to ALS patients. A taurursodiol dietary supplement called TUDCA can be purchased online.
Steve Kowalski, 58, who lives in Boston and takes the drug’s components along with two other approved ALS drugs, credits the regimen with slowing the deterioration. With careful planning and the help of his three grown children, he can still go see his beloved Red Sox, but he says he’s exhausted when he gets home.
Kowalski applauded the FDA’s action on the drug. He prefers to buy a high-quality, approved version of the drug rather than buying a supplement online.
The company’s submission to the FDA was based on mainly 24-week clinical trials and follow-up data from an “open-label” study in which all trial participants were offered the drug.
Typically, the FDA expects drug manufacturers to provide “substantial evidence of efficacy” provided by two well-designed clinical studies. But the agency says a single trial may be sufficient if the study shows a “clinically meaningful and statistically very convincing effect” on prolonging survival or another aspect of the disease.
In March, however, FDA staff gave a mostly negative opinion evaluation — suggested the data were inconclusive — and the agency’s advisers agreed, voting 6-4 to recommend against FDA approval. Patients and advocates flooded the FDA with more than 10,000 emails pleading for approval.
In a rare move, the FDA held a second advisory meeting this month to review additional analysis submitted by the company. Once again, FDA staff a memo that there is insufficient evidence of efficacy to approve the drug.
But the tone of the meeting was different noticeably from the first session. yes, yes in the beginning Dunn acknowledged that the data on the drug raises numerous questions, but also emphasized the “huge unmet medical need” for ALS. He said the agency has the legal authority to be flexible. And in a highly unusual move, Dunn asked Amyly officials if they would voluntarily pull the drug off the market if the big trial failed; they said they would.
Panel with several outside experts on the advisory committee changing positions confirmation is recommended 7-2.
The debate over the drug has echoes of the battle over the controversial Alzheimer’s drug Aduhelm, which was approved by the agency in June 2021. Critics said there was little evidence of the drug’s effectiveness, and Medicare refused to cover it except in trials. The drug market collapsed, Never get bored with patients or doctors.
But ALS doctors insist that ALS medicine is different. They noted that even if the benefit was modest, it met its primary goal in the trial. And they argued that even small gains are meaningful to people with the disease.
The FDA said the drug does not pose major safety concerns; the most common adverse reactions were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. The agency added that the bile acid taurursodiol may worsen diarrhea in patients with disorders that inhibit bile acid circulation, and urged those individuals to speak with a specialist before receiving treatment.
Canada recently conditionally approved AMX0035. Amylyx can sell the drug there as long as the treatment’s benefits are confirmed by a larger trial.
