The lecanemab story is not getting any less tangled. It’s gradually come out that three patients in the trial of the anti-amyloid antibody died while on some sort of anticoagulant therapy – these were uncovered one by one in stories at Stat and here at Science. If I weren’t such a sunny optimist I’d say “three patients so far”. Eisai (the drug’s developer) has sort of been pulled along on this story, because to the best of my knowledge they have not mentioned any of these cases until they were reported. And they have continued to state their opinion that lecanemab played no role in any of these deaths.
But this latest report makes that less clear as well. It turns out that the company revised the clinical consent form given to patients during the trial to include language about increased risk of death with the combination of lecanemab and anticoagulants: “While the overall risk of a major brain bleed is low with [lecanemab] treatment, the risk is higher in people who are also taking blood clot prevention medications. This risk is estimated to be more than 1 in 100 people, but less than 5 in 100 people. . .Bleeding in the brain, especially when you are taking medications that prevent blood clots, can be serious and can even lead to death. It is important to consider the risk of bleeding in your brain with the investigator before deciding whether or not to continue your participation in this study”
That’s not so easy to square with earlier public statements like this one: “. . .all the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause. . .” The latest story notes that the language in Eisai’s consent form was strengthened over time, but it’s not clear how quickly or when these versions propagaged out to the trial centers or to the patients. The deaths have occurred in the open-label extension phase of the clinical trial, from what I can see.
So this raises some tough questions about the FDA review of the antibody and what its labeling might be. And this just highlights what a mess the agency’s earlier approval of Aduhelm has created. Not only do you have that precedent to deal with – if Sulla got his antibody approved, why not mine? – but that very approval is still being questioned. See this report from the House of Representatives, which states that the relationship between Biogen and the FDA was out of the ordinary during the approval process, that they “inappropriately collaborated” on the text of briefing documents, and that the FDA did not follow its own rules on documenting the meetings between the parties. This was not a confidence-building exercise. And it’s not going to make the eventual deliberations over lecanemab any easier. But hey, accelerated approval is expected to be granted this week, so it looks like we’ll sort all that out while the drug is being sold to patients.
You’ll note that the parts of this post that talk about lecanemab reference Eisai, while the parts that reference Aduhelm reference Biogen. In reality, though, both these antibodies are part of a collaborative effort between the two companies. Biogen seems to have taken the regulatory lead on Aduhelm, with the results just mentioned, and it looks like Eisai decided that surely they could do a better job of it for lecanemab. Reports of tension between the two companies on this issue don’t seem to be going away.
