The FDA approval for aducanumab left clinicians with little guidance on how to select the right patients and ensure their safety. At this year’s Alzheimer's Association International Conference, leading clinicians presented appropriate-use recommendations that helped fill the void. These include not prescribing the drug to people with cerebral amyloid angiopathies or people on blood thinners, and monitoring vascular health with frequent MRIs. Clinicians welcomed the guidelines and were hungry for more.
At AAIC, leading Alzheimer’s clinicians plug gaps in the FDA label. They urge exclusion of people with cerebrovascular risk, and an MRI monitoring bonanza. Meanwhile, clinical rollout starts slow, with major hospitals declining to administer.
Data from a Phase 2 trial also suggested that when amyloid dropped in treated brain, plasma p-tau217 followed suit. Using a CAMD progression model, Lilly claims the biomarker responses correlated with slower decline.
Initial results from the first trial of an antisense oligonucleotide against tau in Alzheimer’s are in. BIIB080 appears safe and curbed total tau and phospho-tau 181 levels in the CSF. Clinical outcomes were not assessed.
Biogen sponsors an observational study on the drug’s effects; no word yet on the FDA-required Phase 4 trial. Meanwhile, researchers suggest other ways to test efficacy.
While payers public and private are deliberating whether or not to cover this first-in-class drug, the health economics group ICER re-affirms its original conclusion that aducanumab is overpriced.
Patients taken off the drug continue to outperform those who were never on it, and decline slows even more once treatment resumes. Cognition and plasma Aβ changes are consistent with disease-modifying effect.
Scientists worry about trial recruitment and retention, and discuss whether upcoming trials should allow aducanumab as a background therapy.
In the wake of the controversial thumbs-up for Aduhelm, the U.S. federal government is probing not only aducanumab’s price and approval history, but also the FDA’s accelerated approval pathway in general.
In an open-label Phase 2 study, fluid biomarkers suggested the anti-sortilin antibody restored lysosomal function and reduced neuroinflammation in people with symptomatic FTD. Tantalizingly, participants worsened less than historical controls.
Scientists are testing passive and active immunotherapies that take down pyroglutamate Aβ, and a combo Aβ/tau vaccine.
Single-nuclei expression analysis identified different cell clusters from people who carried autosomal-dominant Alzheimer’s mutations or risk variants for late-onset AD. Also, microglia RNA-Seq goes big.
AD risk scores based on gene expression in microglia associate with having amyloid plaques, and a microglial genomic atlas displays how variants influence gene expression. Polygenic variation in neurons sways cognition.
Decades before tangles become rampant, the biomarker p-tau231 rises in both CSF and plasma. More surprising: neuroinflammation markers do, too.
Markers of neuronal injury rose in plasma within a few months of severe COVID-19, then fell back to normal by six months. Some cases with brain symptoms had lower Aβ and higher tau in their blood.