Safe, but not effective

Pharmaceutical giant Eli Lilly has basically given up on its candidate Alzheimer’s treatment, solanezumab (they’re still trying for one special genetically-driven subtype).

In a Herald story in 2015, the lead was

The first drug that slows down Alzheimer’s disease could be available within three years after trials showed it prevented mental decline by a third.

That was clearly overstating the case. Previous trials has failed to find the benefits they were looking for; this report was based on hints of benefit in a new trial earlier in the disease — a reasonable hope, but nothing like good evidence.

Last year, the company changed the ‘primary endpoint’ of the trial — the definition of what they were hoping to find. That’s usually not a good sign. And it wasn’t.  The company now says

there was no scientific basis to believe they would find a “meaningful benefit to patients with prodomal Alzheimer’s disease.”

Alzheimer’s is an especially difficult condition to research, in part because scientists don’t have a good handle on exactly what’s going wrong. Solanezumab binds to the amyloid protein that causes plaques, enabling it to be removed. That makes a lot of sense as an approach — it wasn’t successful this time. Finding that out was very time-consuming and expensive, because the only way is to run large, long-term randomised trials in people with early-stage disease.

For some drugs and some conditions, you can find out about effectiveness easily: we know Sudafed works for nasal congestion, because it’s obvious. We knew penicillin worked in septicaemia and pneumococcal pneumonia , because of all the people who didn’t die. It took a lot more effort to learn than penicillin works for preventing rheumatic fever. And studies in chronic, slow-moving diseases are far harder than that.

Solanezumab is safe, unlike some previous drugs with similar mechanisms.  It’s an example of a treatment for a serious disease that would have been available years ago if it weren’t for FDA regulation. Millions of people with early dementia could have bought it and used it. It still wouldn’t work.