A bombshell hit the news yesterday (11/20/22) about a breakthrough treatment for Alzheimer’s disease.  But the drug company announced the same news two months ago in the form of a press release.  Today’s story was merely about a formal presentation of the results at an Alzheimer’s conference that added some important safety data.  Here’s my blog post from September.

The drug is called lecanemab, and as its last three letters indicate, it’s a monoclonal antibody – in this case directed against the beta-amyloid protein.  That’s present in an abnormal, aggregated form in brain cells in Alzheimer’s but not in PSP.  In the trial, the antibody solution was infused intravenously every two weeks for 18 months and compared with a group of participants receiving placebo infusions.  The news was that lecanemab slowed the rate of worsening of Alzheimer’s by 27%.  This is great news from the PSP standpoint because it’s the first time that a monoclonal antibody was shown to slow progression of any neurodegenerative condition, even if it’s a different one.  We call that a “proof of principle.”

Today’s new information on the drug’s safety was most notable for a potentially serious issue called hemorrhagic encephalitis.  That’s where areas of the brain tissue undergo swelling and/or bleeding.  That combination is evidence of inflammation, the equivalent of a very sore arm after a Covid shot.  Among the 898 participants with AD who received active lecanemab over the 18 months of the trial, 13% had swelling, but for the 897 receiving placebo, the figure was 2% – a major difference.   For bleeding, the proportions were 17% for lecanemab and 9% for placebo – a minor difference.  Fortunately, none of those participants suffered important or permanent symptoms from the swelling or bleeding, which in most cases would not even have been suspected without the trial’s routine brain MRIs, and in all cases resolved in a few weeks.  However, one wonders how serious the problem could hypothetically be in a tiny percentage of people — too small a fraction to be detected in the 897 on lecanemab in this study.

The group on active lecanemab was a bit more likely than the placebo group to report a variety of serious side effects unrelated to brain swelling or bleeding: 14% vs 11%; and the lecanemab patients were more likely to drop out of the study because of other, assorted side effects: 7% vs 3%.

Now the FDA and Medicare/Medicaid have to decide if they’ll approve this treatment or if the cost (whatever that might turn out to be) and side effects outweigh the benefit. Or, they may require another large trial first.

So, the takeaway for those with PSP is that it’s possible to modestly slow the rate progression of a neurodegenerative disease with a monoclonal antibody treatment with probably only mild risk. The numbers about the hemorrhagic encephalitis are not to be ignored.  But I think that if a hypothetical treatment for PSP gave similar risk and benefit, and the out-of-pocket cost is affordable, I think the majority of people with PSP would ask where to sign up.