Kateryna Kon/Science Picture Library through Getty Photographs
Medicare finalized its resolution to limit its protection of Aduhelm, Biogen’s new Alzheimer’s illness drug, on April 8, 2022.
The choice means solely sufferers who’ve enrolled in medical trials will obtain Medicare protection for Aduhelm, which fits by the generic drug identify of Aducanumab.
Due to the restrictions, many Alzheimer’s sufferers could also be unable to make use of the drug. With out Medicare protection, Aduhelm’s annual price is US$28,200, or $2,350 a month, a value that’s prohibitively costly for many Individuals.
What’s extra, not everybody with delicate Alzheimer’s will have the ability to enroll in a medical trial attributable to location or different logistical points. And a few of these within the trial could also be randomized to solely obtain a placebo.
Medicare’s ruling clashes dramatically with the Meals and Drug Administration’s resolution in June 2021 to approve Aduhelm for all Alzheimer’s sufferers with out restrictions.
This can be a departure for Medicare, which nearly at all times pays for medicine the FDA approves, no less than for licensed makes use of.
Biogen has criticized Medicare’s resolution, saying the added necessities “would considerably prohibit and delay affected person entry to an FDA-approved remedy for a progressive illness.”
However the core of the difficulty surrounding this drug is straightforward: Does it really work?
Combined trial outcomes
As a doctor and researcher who investigates the efficacy of medicines, I’ve been watching this story unfold over the previous yr. As of proper now, I’m sure of 1 factor: With 6 million folks in america affected by Alzheimer’s, and present remedies solely marginally efficient, there’s a determined want for medicines that may gradual the illness.
However the proof on Aduhelm to this point is contradictory. Two Section III medical trials have been stopped early after an impartial committee, appointed by Biogen, analyzed the info and reported the research have been unlikely to indicate Aduhelm would show a profit. This isn’t uncommon; medical trials are sometimes stopped when early knowledge suggests a drug is not going to work.
After that evaluation, Biogen introduced it did discover advantages that have been statistically important in one of many trials. This got here after evaluating outcomes for 318 individuals whose knowledge was not out there in time for the preliminary committee evaluate. That new knowledge confirmed the cognitive operate of individuals within the high-dose group declined 23% extra slowly than these within the placebo group. The low-dose group confirmed no profit.
Whereas the results on cognitive decline could appear ambiguous, Aduhelm indisputably reduces sufferers’ amyloid plaques. It was on this foundation that Biogen sought approval for Aduhelm via FDA’s accelerated approval pathway, the place medicine treating a severe sickness might obtain expedited approval if they’re fairly possible to offer a medical profit based mostly on another marker, comparable to amyloid plaque burden.
Background on Aduhelm
Aduhelm is a monoclonal antibody remedy delivered as an infusion. The drug targets amyloid, a protein that clumps within the brains of Alzheimer’s sufferers.
Whereas Aduhelm does cut back amyloid plaques in sufferers’ brains, so do many different medicines that haven’t been proven to gradual cognitive decline. It might be that decreasing amyloid plaques doesn’t essentially enhance cognitive operate in Alzheimer’s sufferers.
On the core of the query is the amyloid speculation, which has been a central idea of Alzheimer’s analysis for many years. Merely put, the speculation assumes that accumulation of the peptide amyloid-B is the first reason for Alzheimer’s. Many researchers consider that it initiates a cascade of processes that embrace irritation and the formation of neurofibrillary tangles, made up of the protein tau, inside mind cells. That is thought to result in dysfunction of the communication factors between mind cells referred to as synapses, which in the end results in cell loss of life.
However amyloid plaques are sometimes discovered within the brains of people who wouldn’t have Alzheimer’s. The decreased cognitive operate seen in Alzheimer’s is extra intently correlated with the quantity and site of intracellular tau-tangles. It might be that these with plaques however no signs have an early stage of Alzheimer’s.
Dangers and ripple results
Whereas the advantages of Aduhelm stay murky, some dangers are clear. The identical Section III trials confirmed that 41% of sufferers who obtained the excessive dose of Aduhelm – the dose which will have led to cognitive advantages – skilled cerebral swelling or hemorrhage. Though nearly all of these have been minor and asymptomatic, a 75-year-old lady within the trial died after experiencing mind swelling and seizures. The danger was thought of excessive sufficient for the FDA to require the corporate to put a warning on Aduhelm’s label, advising physicians to observe sufferers and acquire two MRI mind scans throughout the first yr of remedy.
Sufferers chosen for the Section III research have been excluded if they’d any of the numerous medical issues widespread for older folks. This contains cardiac issues, using blood thinners or impaired liver or kidney operate. These chosen sufferers, who could also be more healthy than these in most people who would obtain the medicine, underwent not two however seven MRIs for monitoring. MRIs are costly procedures; they increase the true price of Aduhelm by about 20%.
Different anti-amyloid immunotherapy medicines are within the pharmaceutical pipeline. Extra knowledge might emerge to recommend these medicine delay development of Alzheimer’s, however to this point, the comparatively minor cognitive advantages seen don’t appear to match the strong discount in amyloid plaques. Whereas it’s indeniable that Aduhelm can constantly and convincingly cut back the extent of amyloid plaques within the mind, the cognitive profit it gives to sufferers stays doubtful. This discrepancy speaks to the complexities of Alzheimer’s – and the holes that stay to be stuffed within the understanding of this horrible illness.
[Get the best of The Conversation, every weekend. Sign up for our weekly newsletter.]
Andrew Williams doesn’t work for, seek the advice of, personal shares in or obtain funding from any firm or group that may profit from this text, and has disclosed no related affiliations past their tutorial appointment.