Aduhelm is still looking for some respect

Two basic issues with Aduhelm are still in debate:

• Does it have to cost so much?
• How well does it really work?

In early November, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) gave Aduhelm a no-confidence vote on both counts, when Biogen applied for a license to advertise their product.  CHMP may revisit the question later, but this was nevertheless a strong rebuke.  It shouldn't surprise us that sales are less than what Biogen had predicted ... and hoped for.

There is, however, some promising new evidence about its effectiveness, at least in meeting secondary objectives.  If you read Beating the Dementia Monster, you know that both the presence of amyloid plaques and tau protein tangles are markers for development of the disease.  The rationale for Aduhelm was that it would remove amyloid plaques, but researchers were also keeping an eye on the presence of "bad" tau in the cerebrospinal fluid and in blood.  So, while the primary objective is to at least slow the progress of memory loss, two secondary objectives are to reduce the amyloid plaques and tau proteins.  The trials showed that the amyloids can be removed, but what about the tau?

There's some new evidence that Aduhelm does lower tau.  During the trials for aducanumab (the generic name for Aduhelm), blood samples were taken from many test participants, and the samples were retained.  As it happens, the technology for measuring tau has been improving steadily, and the concentration of the specific "bad" tau proteins was more recently measured.  The new measurements found that the tau rose about 9% in those who were on the placebo (620 participants), signaling that the disease was continuing to progress.  But it fell by as much as 15% among those who were receiving aducanumab infusions (571 and 624 participants receiving different doses).  

Unfortunately, it has been very challenging to correlate changes in beta amyloid and tau with the meaningful changes in cognition that we really want.

So how do we sort all of this out going forward?  Biogen is making one contribution by creating a registry to track outcomes of all Alzheimer's disease-modifying treatments.  How many treatments are there?  So far, just one -- Aduhelm.  But we anticipate that 2022 will bring a few more.  Lecanemab, (or BAN2401) and donanemab appear to be on the FDA's fast track and could be out there soon.  So fresh data should accumulate.