F.D.A. Approves Alzheimer’s Drug

Aducanumab, or Aduhelm, is the first new Alzheimer’s treatment in 18 years and the first to attack the disease process. But some experts say there’s not enough evidence it can address cognitive symptomsThe Food and Drug Administration  approved the first new medication for Alzheimer’s disease in nearly two decades, a contentious decision made despite opposition from the agency’s independent advisory committee and some Alzheimer’s experts who said there was not enough evidence that the drug can help patients.

The drug, aducanumab, which will go by the brand name Aduhelm, is a monthly intravenous infusion intended to slow cognitive decline in people with mild memory and thinking problems. It is the first approved treatment to attack the disease process of Alzheimer’s instead of just addressing dementia symptoms. Biogen, its manufacturer, announced that the list price would be $56,000 a year. In addition, there will most likely be tens of thousands of dollars in costs for diagnostic testing and brain imaging. Recognizing that clinical trials of the drug had provided incomplete evidence to demonstrate effectiveness, the F.D.A. granted approval for the drug to be used but required Biogen to conduct a new clinical trial. If the new trial, called a Phase 4 trial, fails to show the drug is effective, the F.D.A. can — but is not required to — rescind its approval.

About six million people in the United States and roughly 30 million globally have Alzheimer’s, a number expected to double by 2050. Currently, five medications approved in the United States can delay cognitive decline for several months in various Alzheimer’s stages. Patient advocacy groups had lobbied vigorously for approval because there are so few treatments available for the debilitating condition. Some other drugs in clinical trials are more promising, but they are most likely three or four years away from potential approval.

The F.D.A. advisory committee, along with an independent think tank and several prominent experts — including some Alzheimer’s doctors who worked on the aducanumab clinical trials — said the evidence raised significant doubts about whether the drug is effective. They also said that even if it could slow cognitive decline in some patients, the benefit suggested by the evidence would be so slight that it would not outweigh the risk of swelling or bleeding in the brain that the drug caused in the trials.

The data included in the applicant’s submission were highly complex and left residual uncertainties regarding clinical benefit,” the F.D.A.’s director of the Center for Drug Evaluation and Research, Dr. Patrizia Cavazzoni, wrote on the agency’s website. But, she said, the agency had decided to approve the drug through a program called accelerated approval, which is designed “to provide earlier access to potentially valuable therapies for patients with serious diseases where there is an unmet need, and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit.” Michel Vounatsos, Biogen’s chief executive, hailed the approval and said in a statement, “We are committed to sharing our future insights about Aduhelm with the scientific community as we collect more data from the real-world use of this treatment.

Source: https://www.nytimes.com/

Biogen Nabs Speedy FDA Review For Alzheimer’s Drug

Biogen’s aducanumab is inching closer to an FDA decision. The Big Biotech, along with partner Eisai, announced  that the FDA accepted its regulatory submission for aducanumab, its once-failed Alzheimer’s drug—with priority review to boot. The agency expects to decide the fate of the treatment by March 7. Along the way, it will hold an advisory committee meeting. It has not set a date for the meeting, but Jefferies analyst Michael Yee expects it sometime in the first quarter of 2021.

The FDA’s acceptance of the aducanumab BLA with Priority Review is an important step in the path to potentially having a treatment that meaningfully changes the course of Alzheimer’s disease,” said Michel Vounatsos, Chief Executive Officer at Biogen.

How the FDA rules on aducanumab will show how far the FDA and its commissioner, Stephen Hahn, M.D., are willing to diverge from its established approval standards. Under U.S. law, companies need to show “substantial evidence of effectiveness to win approval.

Source: https://investors.biogen.com/

https://www.fiercebiotech.com/

Breakthrough In The Fight Against Alzheimer’s

In a shocking reversal, Biogen (BIIB) said that it would resurrect an Alzheimer’s drug that the company previously said had failed and will ask the Food and Drug Administration (FDA) to approve it. The company said a “new analysis of a larger dataset” showed that the drug, aducanumab, reduced clinical decline in patients with early Alzheimer’s disease on multiple measures of the drug’s effectiveness. That directly contradicts a decision in March to halt studies of the therapy based on the recommendations of an independent monitoring board that was charged with protecting patients in the study. Aducanumab’s failure sent shock waves far beyond Biogen. It was thought to be the last of a series of drugs—the previous ones, from many different drug companies, all failed—that targeted a protein in the brain called beta amyloid. After Biogen’s announcement in March, most researchers and biotechnology executives saw little hope for a drug that would help patients with Alzheimer’s disease even as cases mount.

Biogen said that it conducted a new analysis in consultation with the FDA of a larger data set from the discontinued studies. The new analysis includes additional data that became available after the previous analysis showed the studies were “futile”—that it had no chance of succeeding. Biogen said that the new data show aducanumab is “pharmacologically and clinically active” and that it reduced patients’ clinical decline based on the results of a survey called Clinical Dementia Rating-Sum of Boxes (CDR-SB), which was the main goal of both studies.

With such a devastating disease that affects tens of millions worldwide, today’s announcement is truly heartening in the fight against Alzheimer’s. This is the result of groundbreaking research and is a testament to Biogen’s steadfast determination to follow the science and do the right thing for patients,” Michel Vounatsos, Biogen’s chief executive, said in a statement. “We are hopeful about the prospect of offering patients the first therapy to reduce the clinical decline of Alzheimer’s disease and the potential implication of these results for similar approaches targeting amyloid beta.”

Al Sandrock, Biogen’s head of research and development and chief medical officer, said in his first interview about the new results that his team could only find one previous instance where a trial was stopped for futility and then it turned out to be positive. “I have to pinch myself because I almost don’t believe it yet,” Sandrock said. “It’s so amazing to have this change from March. But I’m also very, very happy because… I know people with mild cognitive impairment and I felt like I had let them all down.

By June, as Biogen analyzed the full data set, researchers started to realize that a different picture was emerging of aducanumab, Sandrock said. The reason was because of changes that Biogen had made to the study late in the game. Initially, the company worried about a potential side effectbrain swelling—and limited the dosage of the drug. But later patients were allowed to receive higher doses of the medicine.

Source: https://www.biogen.com/
A
ND
https://www.scientificamerican.com/

Early-Stage Detection Of Alzheimer’s In The Blood

Two major studies with promising antibodies have recently failed – possibly because they have been administered too late. A new very early-detection test gives rise to hope. Using current techniques, Alzheimer’s disease, the most frequent cause of dementia, can only be detected once the typical plaques have formed in the brain. At this point, therapy seems no longer possible. However, the first changes caused by Alzheimer’s take place on the protein level up to 20 years sooner. A two-tier method developed at Ruhr-Universität Bochum (RUB) can help detect the disease at a much earlier stage. The researchers from Bochum published their report in the March 2019 edition of the journal “Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring”.

This has paved the way for early-stage therapy approaches, where the as yet inefficient drugs on which we had pinned our hopes may prove effective,” says Professor Klaus Gerwert from the Department of Biophysics at RUB.

In Alzheimer’s patients, the amyloid beta protein folds incorrectly due to pathological changes long before the first symptoms occur. A team of researchers headed by Klaus Gerwert successfully diagnosed this misfolding using a simple blood test; as a result, the disease can be detected approximately eight years before the first clinical symptoms occur. The test wasn’t suitable for clinical applications however: it did detect 71 per cent of Alzheimer’s cases in symptomless stages, but at the same time provided false positive diagnoses for nine per cent of the study participants. In order to increase the number of correctly identified Alzheimer’s cases and to reduce the number of false positive diagnoses, the researchers poured a lot of time and effort into optimising the test.

As a result, they have now introduced the two-tier diagnostic method. To this end, they use the original blood test to identify high-risk individuals. Subsequently, they add a dementia-specific biomarker, namely tau protein, to run further tests with those test participants whose Alzheimer’s diagnosis was positive in the first step. If both biomarkers show a positive result, there is a high likelihood of Alzheimer’s disease. “Through the combination of both analyses, 87 of 100 Alzheimer’s patients were correctly identified in our study,” summarises Klaus Gerwert. “And we reduced the number of false positive diagnoses in healthy subjects to 3 of 100. The second analysis is carried out in cerebrospinal fluid that is extracted from the spinal cord.

Now, new clinical studies with test participants in very early stages of the disease can be launched,” points out Gerwert. He is hoping that the existing therapeutic antibodies will still have an effect. “Recently, two major promising studies have failed, especially Crenezumab and Aducanumab – not least because it had probably already been too late by the time therapy was taken up. The new test opens up a new therapy window.”

Source: https://news.rub.de/