What’s good for the goose . . . ?

Biogen is currently testing an anti-sense oligonucleotide drug called BIIB-080 in patients with mild cognitive impairment and very mild Alzheimer’s disease. The goal would be to slow or prevent their conversion to full-blown Alzheimer’s disease. Today someone posted a comment asking if I thought this could work for PSP. I thought this could make a good, brief post:

Biogen has an early-phase trial of BIIB080 in Alzheimer’s, and there’s no reason to think it wouldn’t work as well in PSP.

Actually, the Alzheimer’s trial is mostly for people with “mild cognitive impairment” and the measure of success would be preventing progression (“conversion,” as it’s called) to full-blown Alzheimer’s. They are also enrolling some patients with mild AD, hoping to prevent progression to moderate stages. If the people at Biogen feel that BIIB080 should first be tested in such an early disease phase, that could be why they chose Alzheimer’s over PSP: there is no known equivalent of mild cognitive impairment for PSP.

Another reason Biogen might be starting with AD is the ready availability of a test for beta-amyloid in the brain in the pattern specific for that disease. It’s called an Amyvid scan, and participants in the BIIB080 trial have to show an AD pattern on the scan to qualify. There is no equivalent, road-tested, sensitive and specific diagnostic test for PSP, which means that a much larger trial would be necessary to overcome the “statistical noise” caused by people with a false-positive diagnosis of PSP.

The diagnostic criteria for PSP do define a state called “suggestive of PSP,” but there are still no data on what fraction of those individuals eventually progresses to probable or definite PSP, or how long it takes. On the other hand, there are excellent such data on the conversion of MCI to Alzheimer’s.

A couple of examples of symptoms that would result in a diagnosis of “suggestive of PSP” are repeated falls and slow downward eye movements. As you can tell, such symptoms in isolation are not very specific for PSP, so a trial enrolling such patients would have to have many hundreds of particicpants for a statistically useful fraction of them to convert to possible, probable of definite PSP, especially over only a 12-month period. Furthermore, the size of the trial would have to be large enough for the conversion rate among the recipients of the active drug to be validly compared to the rate among those on placebo.

So, my guess is that if BIIB080 works in mild cognitive impairment and very mild AD, Biogen will test it in PSP. But if a good pre-clinical marker for PSP becomes available, then it would much more practical to try such treatments in pre-clinical PSP.

But there are other drug companies with other anti-tau ASOs. One, from Novartis, is already enrolling patients. Others are approaching clinical trials.

2 thoughts on “What’s good for the goose . . . ?

  1. Dear Dr Golbe,
    Greetings and once again, thanks you for the wonderful work you are doing by providing a balanced view on the progression of research in PSP.

    Based on the fact that you have been working in this field over decades and to date there has been no cure for PSP, what is your view for a possible drug been developed in the next year?



    • Mervyn:
      The scientists are constantly surprising me with their new ideas for drug treatment of PSP. I know of six different drugs currently in trials for PSP and another six approaching trials in the next year or two. But I have no way to know which, if any, are likely to succeed, and neither does anyone else.
      Keep in mind that once a drug enters Phase I clinical testing, it typically takes a couple of years of small-scale trials just to get permission from the FDA to do a “pivotal” trial (that is, a large Phase IIb or Phase III trial that, if successful, would allow the FDA to approve the drug for sale). Then, the pivotal trial typically takes about two years. That happens sooner in the precious few cases where the independent monitoring committee sees that the trial drug is so dramatically successful that it would be unethical to continue to withhold it from the trial participants on placebo and the general public. Let’s all hope for that!
      Dr. G

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