Alzheimer’s: breakthrough or failure

Some new headlines:

• Unprecedented Alzheimer’s drug slows disease by 80 per cent 
• Promising Alzheimer’s treatment flops in new trial, crushing hopes 
• Alzheimer’s breakthrough as new pill taken twice a day STOPS disease from shrinking brain
• First drug to halt Alzheimer’s tested by scientists
• Alzheimer’s Maverick TauRx Tries To Weave Success From Failed Trial
• Alzheimer’s Drug LMTX Falters in Final Stage of Trials
• Drug ‘may slow’ Alzheimer’s brain death

Admittedly, the shouty headline is from Daily Mirror, but the other positive ones include the BBC and New Scientist. And, yes, they are talking about the same trial of the same drug.

How can this possibly happen? And who’s right? Here’s the full press release from the conference. It starts off

A clinical trial of LMTM (TauRx Therapeutics, Ltd.) in people with mild to moderate Alzheimer’s failed to demonstrate a treatment benefit in the primary analysis of the full study population in both doses tested. However, in a pre-planned analysis of a small subgroup of the study population that received LMTM as a monotherapy, there was a statistically significant benefit on cognitive and functional outcomes, and slowing of brain atrophy.

The  trial compared two doses of LMTM to placebo, in 891 people, and didn’t find the benefit it was looking for. The press release doesn’t give the results, so we don’t know if there was modest evidence of benefit or basically nothing.

They then compared the 90-odd people who were taking LMTM and no other treatment to the 250-odd who were taking placebo. It’s that relatively small group that has the impressive results.

Reasons behind the negative headlines include

• the regulatory/investment aspect: these results are unlikely to get the drug approved, so TauRx won’t be getting the truckfulls of money they’d be anticipating if the whole trial had been successful
• subgroup analyses are often over-optimistic, because you mainly get to see them when they’re the sole redeeming feature of a disappointing set of results
• in fact, getting positive results in a subgroup isn’t at all unprecedented with Alzheimer’s. Eli Lilly are betting a lot that they’ve found the right subgroup and their drug solanezumab will now be successful.
• it’s unusual to compare people getting LMTM but nothing else with everyone on placebo (rather than people getting placebo but nothing else). You’re not guaranteed a fair comparison by randomisation that way.
• in the other direction, it’s hard to see how other treatments (which focus on stimulating the cells that are still working) would counteract the effect of LMTM (which is trying to prevent protein tangles from forming). But biology is weird, so maybe it’s true.

TL;DR: So, would I try to get this drug if I had an AD diagnosis? It would depend on the actual results in the whole trial (which we aren’t told) and on the details of side effects (which we also aren’t told). But I’d certainly have been disappointed by these results.  And New Scientist should be ashamed of themselves.