Patients and advocates are celebrating the approval of a new treatment designed to slow the progression of ALS, a devastating neurogenerative disease that kills most people within five years. The drug, Relyvrio, is only the third ALS treatment cleared by the Food and Drug Administration in almost three decades and the first since 2017.
Brian Wallach, a former Obama administration official who founded the nonprofit group I Am ALS after being diagnosed with the disease, tweeted that the approval has provided "something that is really rare for us; real, tangible hope."
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But the FDA action also stirred controversy. Some people - including FDA staff and some of the agency's own outside advisers - raised concerns about the clinical trial for the drug, saying it had flaws and that the data was not strong enough to warrant an approval.
What does the drug do?
The new therapy is far from a cure. The powdered concoction, which is mixed with water and swallowed or taken through a feeding tube, is designed to slow the disease by protecting nerve cells in the brain and spinal cord destroyed by ALS.
In a 24-week study, 137 patients were randomized to receive Relyvrio or a placebo. The people in the treatment group experienced a 25 percent slower rate of decline in performing activities such as walking, talking and cutting food compared with those receiving a placebo. The data and subsequent analyses also indicated those patients lived several months longer.
When will the drug be available?
In a call with investors Friday, Amylyx, the manufacturer of the therapy, said the treatment will be available in four to six weeks.
How much will it cost?
The Cambridge, Mass., company set a list price of $158,000 a year. That's not what most people will pay, however.
For people with private insurance, Amylyx officials said, the company will provide financial assistance to eliminate co-payments. They also said the drug would be made available without charge to uninsured patients who meet eligibility criteria. And the company is exploring ways to keep down out-of-pocket costs for patients with government coverage such as Medicare and Medicaid.
Calaneet Balas, president and CEO of the ALS Association, said her organization is working to help secure insurance coverage from officials at Medicare, the Department of Veterans Affairs, commercial plans and other payers.
"We expect all payers to cover this and any drug approved for people living with ALS," Balas said in an email.
The price drew criticism from some advocates. A few weeks ago, the Institute for Clinical and Economic Review, a nonprofit group that analyzes evidence on the effectiveness and value of drugs, said a fair price would be $9,100 to $30,600 annually.
Why is the drug controversial?
The ALS drug became part of a larger debate about how the FDA handles drugs for devastating illnesses, especially neurological conditions.
Last year, the agency approved Aduhelm, a medication for Alzheimer's disease, despite opposition from many experts in the field who said the evidence for the drug's effectiveness was scant and confusing. Medicare declined to cover the treatment except for patients in clinical trials. The drug collapsed in the marketplace, never winning acceptance from patients or physicians.
FDA scientists, in reviewing the ALS drug, said the agency typically expects substantial evidence of efficacy based on two clinical investigations, though it can clear a drug on a single "persuasive" trial and confirmatory evidence. The staff appeared unconvinced the medicine met that bar.
The agency's advisory panel seemed of two minds, as well, recommending against approval in March but then voting in favor of approval in September. Some advisers said the FDA should hold off approving the drug until a larger trial - expected to be completed by early 2024 - provided more information.
But the agency has wide latitude in the case of life-threatening diseases that do not have effective treatments and was under intense pressure from patients and advocates to clear the drug. In announcing the approval, the FDA acknowledged there were "limitations" to the data that created uncertainty about effectiveness.
But it concluded the evidence was sufficient and that flexibility was appropriate because of the "serious and life-threatening nature of ALS and the substantial unmet need" for treatments.
Does the drug cause side effects?
The most common adverse events were diarrhea, abdominal pain, nausea and upper respiratory tract infection, Amylyx said. Overall, the FDA concluded the medication was safe.
How do people get ALS?
More than 90 to 95 percent of people with ALS have "sporadic" disease - there is no family history of the illness and the cause is unknown. Scientific evidence suggests that both genetics and environment play a role in the disease, according to the National Institute of Neurological Disorders and Stroke. About 10 percent of patients have "familial" disease, which is thought to be inherited.
Often, ALS shows up initially as cramps or twitching of muscles in the hands or feet, or as slurred speech or trouble swallowing. The illness is often called Lou Gehrig's disease, after the famous baseball player diagnosed in 1939. About 30,000 people in the United States have ALS, with 6,000 new cases diagnosed every year.
Why is it so hard to develop drugs for ALS and other neurodegenerative diseases?
In an interview about neurodegenerative diseases before the FDA announced its decision on Relyvrio, Patrizia Cavazzoni, director of the agency's Center for Drug Evaluation and Research, said attempts to develop drugs for ALS and other ailments face big challenges.
One is a lack of scientific understanding about the biology underpinning the diseases, an understanding that is required for the development of effective therapies, she said. "With cancer, as we have seen, that is an essential step in developing drugs specifically targeted" to the specific type of disease, Cavazzoni said.
Another factor, especially regarding ALS, is the heterogenous nature of the disease. The illness affects different people in different ways. Cavazzoni said scientists need to learn more about the different patterns of disease progression and the biological indicators.
What are the other drugs approved for ALS?
The FDA has approved two other medications for ALS. Rilutek, which prolongs life by a few months, was approved in 1995 and now is available as a generic called riluzole. Radicava, which was approved in 2017, slows the loss of physical function - meaning a patient's ability to walk, feed themselves and swallow.
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