Great news from Biogen about an antisense oligonucleotide (ASO) designed to reduce production of the tau protein. 

First, some background: Most of you have heard about ASOs, but for a refresher, see these posts of mine from 2022 and 2026.  Here’s a slightly more technical but cutely animated explanation of ASOs from Harvard Medical School:

The elevator version is that an ASO is a short length of RNA that binds and inactivates the brain’s messenger RNA for a specific protein – or an abnormal version thereof – to prevent it from carrying the protein’s genetic code from the DNA to the protein-manufacturing machinery.  In theory, the production of any protein involved in the cause of a disease can be reduced by designing an appropriate ASO to bind to a segment of that protein’s messenger RNA.

The FDA has approved only one ASO so far – for a childhood muscle disorder called spinal muscular atrophy – but dozens of other ASOs are in the development pipeline for other conditions, including tauopathies. Biogen is currently testing its anti-tau ASO, called diranersen (formerly BIIB-080) against Alzheimer’s, by far the most common tauopathy.  A few days ago, they announced the results of a Phase 2 study of its safety and tolerability.  Here’s Biogen’s press release and here’s the description of the trial (without results) in clinicaltrials.gov. 

Diranersen was well-tolerated in people with Alzheimer’s, as expected based on the Phase 1 results.  The big news was that the rate of accumulation of abnormal tau protein aggregation actually did slow down, as measured by levels of tau in the spinal fluid and by positron emission tomographic (PET) images of the tau protein’s distribution in the brain. The press release didn’t say how much slowing occurred, but it was apparently enough to convince Biogen to proceed to a Phase 3 trial and to convince the FDA to let them do so. More details will be presented at the Alzheimer’s Association International Conference in London in July 2026.

The trial was not primarily designed to assess slowing of progression of the participants’ actual cognitive loss, but it gathered that information anyway in various forms.  The primary such test, called the “Clinical Dementia Rating Scale Sum of Boxes,” measures memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. It did not show a statistically significant slowing of progression for diranersen in Alzheimer’s, but the press release hints that there was some slight, statistically non-significant, degree of slowing.  

That’s all about Alzheimer’s. For PSP, a different company, Novartis, is testing a different anti-tau ASO (NIO-752).  It is also well tolerated, as demonstrated by a recently-completed Phase 1 trial.  If the brain’s accumulation of abnormal tau can be slowed down in Alzheimer’s disease, as the Biogen press release claims, then presumably PSP can achieve the same result.  Novartis says it’s still (as of May 15, 2026) analyzing its Phase 1 PSP efficacy results, but those would have to be spectacular to show statistical significance in so small a study.  That company will soon start testing NIO-752 in a Phase 2 PSP trial in the US and other countries, so keep an eye on clinicaltrials.gov for enrollment instructions.

Given these new results of one anti-tau ASO in one tauopathy, what are the prospects for a different anti-tau ASO in a different tauopathy?  I’ll duck the issue and call them promising but far from a slam dunk. That will be the topic of a future post, but what I can say right now is even these modest, preliminary signs of success with ASOs in tauopathies would have been science fiction back when I was in med school 50 years ago.