Sixty seconds on . . . solanezumab
BMJ 2016; 355 doi: https://doi.org/10.1136/bmj.i6389 (Published 29 November 2016) Cite this as: BMJ 2016;355:i6389
More bad news on drugs for Alzheimer’s disease?
Yes, another drug has failed in phase III trials. This one is solanezumab, whose demise was a three act drama that’s finally seen the curtain fall.1 2 3
Was that a surprise?
Not really. Alzheimer’s disease is the graveyard of drug discovery. One study found that of 244 compounds tested between 2000 and 2014 only one was ever licensed, a failure rate of 99.6%.4
That implies everybody’s doing something wrong
Or maybe that Alzheimer’s disease is more complex than the drug companies have assumed. Solanezumab is a biological drug that targeted amyloid protein, a signature of Alzheimer’s disease, and was designed to break up the clumps of amyloid in the brain. Two phase III trials had failed in 2012, but the drug was resuscitated last year after Eli Lilly discerned in the trial data some evidence that it might be slowing the course of the disease in mild cases. It launched yet another trial, which has now also failed.
So that’s the end?
Eli Lilly says that it won’t apply for a licence and is winding up longer term trials.
What about amyloid? Is it the wrong target?
That’s what some say. Others argue that by the time amyloid has formed, it’s too late, so you need to start treatment earlier. But with no reliable tests until symptoms appear, that’s difficult. Yet others say that a different class of drugs, β secretase inhibitors, which aim to stop amyloid forming, may do better. One of those has already failed because it caused liver damage, but others are in trials.
Is there an alternative target?
Amyloid formation is not the only brain change seen in Alzheimer’s disease. Patients’ brains also contain tangles of a protein called tau. The first phase III trial of a drug to prevent these tangles produced some benefits but only in a subset of patients who weren’t taking existing treatments—a puzzling finding.
Footnotes
thebmj.com Margaret McCartney The “breakthrough” drug that’s not been shown to help in Alzheimer’s disease doi:10.1136/bmj.h4064Feature Alzheimer’s disease: still a perplexing problem doi:10.1136/bmj.g4433
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