Drug development is hard work. Failure comes with the territory. You just have to accept it if you want to invest in the sector.
But some diseases, such as Alzheimer's disease, make you question whether accepting the risk is really worth it. Bloomberg cites data from the Pharmaceutical Research and Manufacturers of America that say there have been "101 unsuccessful attempts to develop a treatment for Alzheimer's disease since 1998."
I'm guessing the industry group is counting clinical trials rather than individual drugs. If so, Pfizer (PFE 0.55%), Johnson & Johnson (JNJ -0.46%) and Elan's (ELN) bapineuzumab would count for four failures since it ran four phase 3 trials concurrently that all failed to show an effect. Ditto for Eli Lilly's (LLY 1.19%) solanezumab, which failed two phase 3 trials last year.
But no matter how you count them, it's an awful lot of drugs to fail in a single disease over a 15-year period.
Why?
Simply put, we don't know enough about Alzheimer's disease to know how to treat it.
We know that patients with Alzheimer's disease get plaques in their brains made up of a protein fragment called amyloid beta. The problem is we don't know if those plaques are causing the Alzheimer's or if they're just a symptom of the disease and not the actual cause.
Both bapineuzumab and solanezumab are designed to bind to amyloid beta. In theory, if the protein fragment is sequestered by the antibody, it can't form plaques. As mentioned above, there wasn't much of an effect with either drug.
Lilly tried to block the formation of amyloid beta by inhibiting the enzyme that cuts amyloid beta from the amyloid protein. Unfortunately, semagacestat didn't work. In fact, it made patients worse than those taking placebo.
While the failures point to the amyloid hypothesis being bunk, we can't rule it out completely because it's possible that the drugs are just failing to do their job instead of the more obvious possibility that they're successful, but having less amyloid beta doesn't do anything.
Merck (MRK 0.37%) is betting on the former. It recently moved MK-8931 into a phase 2/3 study. The drug targets a second enzyme that, like semagacestat's target, is required to cut the amyloid beta fragment. Whether the new target will have a better result is anyone's guess. I wouldn't hold my breath.
Early is better?
Another possibility is that by the time doctors are treating patients in the clinic, they've already passed the point of no return.
To test that theory, some drugmakers are testing their drugs in patients with amyloid plaques but without any of the Alzheimer's symptoms. Lilly has developed an imaging diagnostic called Amyvid that can detect the plaques with a PET scan. Researchers from Brigham and Women's Hospital are using Amyvid to determine whether patients should enter a prevention trial that will test Lilly's solanezumab. Roche is testing its drugs' ability to prevent Alzheimer's in a group of people in Colombia that typically show Alzheimer's symptoms around age 45 because of a rare genetic mutation.
High risk, high reward
It's pretty clear why pharmas continue to develop Alzheimer's drugs despite the high failure rate: the lucrative prize for an Alzheimer's drug that works well makes up for the high risk the companies are taking on.
Most investors would be best off staying away from Alzheimer's drugs given the high failure rate; don't become failed attempt No. 102 if you don't have to.
If you do choose to invest in a company that's developing an Alzheirmer's disease drug, make sure it's a big pharma that can afford the hefty development cost and the absorb the inevitable failure.
