[ad_1]
Since Monday, Matthew Schrag’s inbox has been filled with emails from patients and loved ones wondering if there should be hope for a new Alzheimer’s drug. The drug, called aducanumab, was granted express approval earlier this week by the US Food and Drug Administration. The last time the Food and Drug Administration approved a drug for this devastating disease was in 2003.
But Schrag, a neurologist at Vanderbilt University Medical Center in Nashville, is unlikely to prescribe the latest treatment. “We don’t know if it works or not, and the side effects can be really big,” he says.
In the United States, Alzheimer’s disease affects more than six million adults 65 years of age or older. It is the most common cause of dementia and the sixth leading cause of death in this country. After diagnosis, older people live four to eight years, on average, and any treatment that can slow the progression of the disease and improve quality of life is highly sought after by loved ones.
Developed by Massachusetts-based biotechnology company Biogen and marketed by the brand name Aduhelm, aducanumab removes the toxic form of a protein called beta-amyloid. This protein accumulates in the brains of Alzheimer’s patients and can disrupt communication between brain cells. Some experts believe that removing the amyloid plaque may treat the underlying cause of the disease.
In clinical trial data evaluated by the Food and Drug Administration, aducanumab effectively reduced the accumulation of amyloid protein in the brain, and showed signs of marginal cognitive decline. This means that, unlike previously approved treatments, the drug can slow the progression of the disease rather than just targeting the symptoms. But the theory that amyloid is the key is hotly debated, and the FDA’s decision based on anecdotal evidence was quickly criticized.
Patricia Cavazzoni, director of the Food and Drug Administration’s Center for Drug Evaluation and Research, wrote in a news release about the decision. “As a result of the FDA’s approval of Aduhelm, Alzheimer’s patients have an important and critical new treatment to help fight this disease.”
But Schrag and several other scientists are not entirely convinced of the drug’s ability to delay dementia. “The evidence for effectiveness is lacking,” says Schrag. “The clinical benefit was hardly detectable.”
Biogen officials declined to comment for this article.
expedited approval
In the 1980s, scientists examined the DNA of Alzheimer’s patients and discovered mutations in the gene that produces the protein beta-amyloid. The protein is important for neuronal development among other biological activities. Gene mutations cause beta-amyloid to form abnormal clumps called plaques that build up in the brain. Since these plaques were already thought to be the trigger for Alzheimer’s disease, beta-amyloid proteins quickly became the focus of research and drug development.
Although several drug companies have developed compounds that reduce amyloid deposits, they have all failed to stop or reverse dementia. Then, in 2015, early evidence from clinical trials of adiokanumab indicated that clearing of amyloid plaques appears to be accompanied by a somewhat slower decline in cognitive function in some Alzheimer’s patients.
Building on this research, Biogen has created two larger, identical clinical trials called Engage and Emerge. The 3,300 participants—patients with mild cognitive impairment or mild dementia due to Alzheimer’s disease—either received a placebo or a low or high dose of a monthly intravenous infusion of adiokanumab.
Both studies were halted in March 2019 after an independent interim data analysis indicated that aducanumab was “not feasible”. Although the compound removed amyloid deposits, it did not stop or slow cognitive decline and was unlikely to benefit patients.
However, the company re-analyzed the data in October 2019, including additional data from the time the interim data analysis began until the date the trial was terminated. This analysis found that patients in the Emerge trial who took high doses of aducanumab showed 22% slower cognitive decline over 18 months, compared to patients treated with a placebo. No such decreases were recorded among the Engage study patients.
“There is no doubt that it is a statistically demonstrable effect, but the doubt is whether it is clinically significant,” Schrag says. This means that the marginally less cognitive decline recorded in the trial may not necessarily improve patients’ memory.
Critics of the drug also point out its side effects. About 35 percent of all patients treated with aducanumab experienced painful swelling of the brain and, in some cases, bleeding in the brain.
However, Biotech, along with Japanese pharmaceutical company Eisai, sought approval from the Food and Drug Administration on the basis of these statistically positive results. Last November, an independent panel advising the US Food and Drug Administration rejected the drug, arguing that there was not enough evidence to show that the compound benefits Alzheimer’s patients.
On June 7, defying its own advisory committee, the Food and Drug Administration granted rapid approval for the drug. According to the FDA, this type of approval “is intended to provide early access to potentially valuable therapies for critically ill patients where there is an unmet need, and where there is an expectation of clinical benefit despite some remaining uncertainty regarding that benefit.” .”
bad precedent setting
Biogen and Esai now have until 2029 to complete another clinical trial to confirm the drug’s benefits for Alzheimer’s patients. Many experts argue that a third clinical trial, similar to Engage and Emerge’s, would have been a better way forward to break the tie.
“In this case, because previous trials differed, it would have been relatively easy had the drug not been approved to complete another trial in two years” and the Economic Review, which reviewed Independent clinical trial data for aducanumab. “Waiting nine years to see if it helps does not really benefit patients.”
In 2016, the U.S. Food and Drug Administration authorized Exondys 51 to treat Duchenne muscular dystrophy, a rare and fatal genetic condition that affects children’s muscles. The decision was made despite poor effectiveness data and the objections of its advisory committee. The results of an ongoing study to confirm the benefits from administering Exondys 51, which can cost a patient more than $700,000 each year, are still pending.
Aducanumab treatment costs about $56,000 each year. How much each Alzheimer’s patient will pay out of pocket depends on their insurance coverage. Brain scans to monitor for side effects and other associated costs will add a financial burden to patients.
“That’s a huge amount of money for a drug that we’re not sure at all works for a disease that affects millions of people in the United States,” Rend says. Also to his surprise, the US Food and Drug Administration made the drug available to all Alzheimer’s patients, even though clinical trials included only those with mild cognitive symptoms.
“Patient advocacy groups likely have a huge role in convincing the FDA that it is still worth it,” believes Walid Fouad Galad, an internist in Pittsburgh. “They are willing to accept uncertainty.” For example, the Alzheimer’s Association was among those who advocated FDA approval.
Many doctors and scientists now envision difficult conversations with families who may feel guilty if they do not give this drug to their loved ones. But while some people are grateful for the drug’s approval, others find the move troubling.
“We want to support scientific developments and processes, but rush into expensive treatments that may not have any proven results at the expense of others,” says Eli McBroom, the primary caregiver for her 62-year-old mother in Kentucky, who was diagnosed with Alzheimer’s in 2012. People who are severely infected is very risky.”
Experts also hope that such approvals will not stifle research on other Alzheimer’s drug targets.
Mark Diamond of the University of Texas Southwestern Medical Center is studying a protein called tau in the brain that is linked to cognitive loss. Beta-amyloid proteins may trigger Alzheimer’s disease, but he and several other neurologists believe that tau buildup may cause dementia, “which is why I think studies targeting beta-amyloid may have failed to show a good benefit for people,” he says.
Diamond develops treatments that target tau. In the future, when it’s his drugs’ turn for scrutiny, Diamond hopes the FDA will comply with the usually high standards of approval.
[ad_2]
Picture Credit!