“Insanity is doing the same thing over and over again and expecting different results.” It’s a phrase attributed to Albert Einstein, among others, and how one industry veteran views the approach drug makers take in developing treatments for Alzheimer’s—with a twist. For Cameron Durrant, MD, MBA, there’s a hammer involved.
“You whack your thumb with a hammer and it hurts. You whack it again and it hurts, and then you whack it another time and it hurts. Do you think you should put the hammer down?” he asks.
If you’re a pharmaceutical company today intent on developing a drug for Alzheimer’s (AZ) the answer is “No,” according to Durrant, Executive Chairman of Anavex Life Sciences. The hammer in this case is amyloid, long considered by researchers to be behind AZ. It’s the build up of amyloid plaque in the brain that is associated with the disease. So companies have been targeting amyloid and its removal in their search for an effective treatment.
Or as Durrant sees it: hammer whacking their thumbs repeatedly.
“Antibodies and vaccines have been shown to remove amyloid but every study so far says that’s doesn’t matter,” says Durrant. “So, one of the reasons it’s difficult to develop drugs: We’re looking at the wrong drugs and targets, and we seem to be doing that over and over again.”
Recent examples of anti-amyloids that failed in later-stage trials include Neurochem’s Alzhemed (2007) and Myriad Genetics’ Flurizan (2008). Although not touted as an anti-amyloid, the most recent AZ late-stage failure is Pfizer and Medivation’s Dimebon, whose inability to meet efficacy endpoints in Phase III has resulted in job losses at the San Francisco-based Medivation.
So if not amyloid, then what? Target a totally different mechanism like sigma receptors that affect mitochondria, says Durrant. Which is exactly what the investigational AZ drugs in Anavex’s pipeline do. Among them is anavex 2-73, their lead compound due to go into a Phase I European-based trial this year. So far, very, very low doses have shown positive effects, says Durrant, who gives three reasons for why it’s different from all the other compounds in development: it’s oral, disease modifying, and—of course—doesn’t target amyloid.
The graveyard of Alzheimer’s drugs in Durrant’s opinion.
For more on Alzheimer’s drugs in development and an overview of the market, with fresh insight from DIA’s 22nd Annual Euromeeting, be sure to check out Applied Clinical Trials’ April news section in print and online.
To hear more from Dr. Durant on Alzeheimer’s drug development and clinical trials, check out his recent two-part interview below on CHUM Radio Ottawa’s Business@Night (CFRA AM 580) with host Greg Hebert.
One Comment
The AD field will always welcome new approaches targeting disease modification and applauds Dr. Durrant and Anavex’s efforts. That said the majority of imaging (MRI to PET with Ligands) and CSF correlation work with clinical functional changes by ADNI and others points to changes in Amyloid burden and one of the key pathological pathways in the progression of AD. The recent AD clinical trial failures may not be in the target that was selected (amyloid) as much as the subjects used to demonstrate to date this elusive efficacy. Factors such as the stage of their dementia, genetic pre-disposition and the now apparent changing pathophyiology of AD as the disease progresses (Asymtomatic or Prodromal AD, to MCI, to Mild to Moderate and finally to Severe AD) may prove to be more challenging than the target selected.