Recently, two women in Melbourne with Alzheimer's disease found themselves able to complete complex tasks they haven't been capable of for some time. One woman found herself suddenly able to play the piano again, and another the ability to paint.
The apparent reason for their regained abilities is an experimental pill from Anavex Life Sciences (NASDAQ:AVXL) that they've been taking as part of an early stage trial. Could this new drug, named 2-73, be the first to slow, or even reverse progression of this awful disease? If so, how long until it's available to the public?
To answer these questions, it seems we'll have to wait and see. The principal investigator of the 32-patient clinical trial these ladies are enrolled in, Stephen Macfarlane poured water on the excitement these women generated. "It's looking good at this stage," he said. But, "What's required is a much larger trial with a placebo control group to see if the changes we've noticed in this early study are actually real and pan out in a proper and well conducted study."
In other words these women's regained abilities could be due to a placebo effect, because every patient knows they're getting the drug.
A second opinion
Given my limited experience with Alzheimer's patients, I reached out to another expert in an attempt to pin down just how significant these two ladies' regained abilities were with respect to the 2-73 pills they've been taking.
What I learned was, they're basically meaningless. James A. Hendrix, Ph.D., director, global science initiatives, at the Alzheimer's Association, was quick to point out patients over the age of 65 often have several different health problems. When something else bothering them -- think arthritis, asthma, even depression -- is alleviated, some patients appear to have better cognitive abilities.
With respect to clinical trials, Hendrix's remarks were nearly identical to Macfarlane's.
What we need to wait for
To answer the question of whether this pill is a cure or not, we're going to have to wait for Anavex to conduct the only sort of study that the FDA will accept as proof that 2-73 is effective and safe. For a disease as widespread as Alzheimer's, regulators will probably insist on data from a single trial with at least two groups of over 1,000 patients each. Most importantly, they will need to be randomized into two groups, one receiving 2-73, and others a placebo, without anybody's knowledge save for a group of independent data monitors that charge an arm and a leg to run pivotal trials of this sort.
Furthermore, Alzheimer's disease progresses slowly, which means that once such a trial doses the last patient enrolled, it will be years before any meaningful conclusions can be drawn. Until Anavex has data showing statistically significant improvements in efficacy, without side effects, regulators won't even consider an application to market the drug to Alzheimer's patients.
When will Anavex begin a pivotal trial?
So far, that's been the toughest question to answer. In theory, it could begin today, but it doesn't have the necessary financing. The company has never conducted a pivotal trial with any drug, and has nothing to sell but shares of its stock. A much more sensible (and financially responsible) option would be to license 2-73 to a larger company with the means to run a such a large and expensive trial.
It's not at all uncommon for smaller companies with promising Alzheimer's candidates (or any drugs, for that matter) to collaborate with deep-pocketed drugmakers to reduce their own risk and begin generating some revenue to fund further projects. For example, Biogen licensed the most promising Alzheimer's candidate at the moment, aducanumab, from privately held Neurimmune and several others from Eisai.
It's important to note here that Anavex's 2-73 does not function in the same manner as any Alzheimer's candidates that have been put through placebo-controlled studies. That's not necessarily a bad thing. Every drug with potential to slow progression of the disease run through large, placebo-controlled studies has so far failed.
Anavex has begun "preparation" for a pivotal study, but it hasn't set a date to begin. I contacted the company's PR firm to ask if it had received any offers to license 2-73, or whether it was seeking partnerships. The company is "open" to collaboration but will not comment on whether it has received any offers.
Back where we started
As hopeful as I am for the participants in Anavex's trials to date, I'm afraid we can't say anything significant about 2-73's potential to cure or slow the progression of Alzheimer's disease, at least from a regulator's standpoint.
Anavex has no shortage of presentations and press releases suggesting its efficacy, but until it's been compared to a placebo in a larger, blinded study, we really can't call it a cure.
As to when, or how, it will run the necessary trials to support an application that could eventually lead to an FDA approval, we can't say that either. I suggest Anavex shareholders keep their fingers crossed in hopes some company will collaborate soon. For now we're left with more questions than answers.