“Repositioning” is the process of testing a drug that is already FDA-approved or that has been proven safe in a clinical trial for a certain indication, to determine whether the drug might be efficacious in the treatment of another therapeutic area, such as Parkinson's disease (PD). Repositioning can drastically reduce the timeline for getting a drug into clinical testing.

The Michael J. Fox Foundation (MJFF) has paid particular attention to repositioning over the past few years, launching its first-ever repositioning specific Request for Applications (RFA) in 2010, funding nine research teams for awards totaling $3.4 million. Projects of interest from this RFA focused on a tuberculosis vaccine, the high blood pressure drug isradipine, and the antidepressant duloxetine, to determine if any of these drugs might have disease modifying potential for PD.  MJFF also supported a team investigating if a compound used to treat Attention Deficit Hyperactivity Disorder (ADHD) might also provide symptomatic relief for Parkinson’s patients. 

Currently, the Foundation is also supporting a Phase 4 clinical trial of naltrexone, a drug marketed for alcohol abuse, to treat compulsive disorders associated with PD. And just this past month, a team of London-based researchers supported by the United Kingdom’s Cure Parkinson’s Trust reported positive clinical study results for the development of a diabetes drug called exenatide as a disease-modifying treatment for PD.

Enthusiasm for repositioning continues to grow, from disease foundations like MJFF, to pharmaceutical companies, to the government: Just last month, the National Institutes of Health (NIH) announced that it would fund nine research projects totaling nearly $13 million into previously abandoned drugs, for new indications including Alzheimer’s disease.  

One pharmaceutical company that has dedicated a new focus to repositioning projects, and which is working closely with MJFF, is AstraZeneca.  Here, we speak with their Vice President, Emerging Innovations, (and repositioning expert) Don Frail, PhD, about the current state of repositioning on the whole, and why his company is so interested in investing in repositioning projects moving forward. 

MJFF: Why has repositioning become so popular in the drug development sphere over the past few years?

Don Frail: Most people don’t realize that the majority of drugs on the market are also approved for additional indications than the one they were first approved for. 

The classic example is Viagra, which was initially being developed for angina.  While it proved to be safe early on, it didn’t end up meeting desired endpoints in clinical studies. Of course, later trials showed that it could work for erectile dysfunction. And then, even after this, Viagra was again repositioned for pulmonary arterial hypertension.

Companies have always looked to consider other indications for existing drugs. But I think over the past few years, based on the changing industry climate, drug companies such as ours have looked to crowd source ideas, co-create ideas, and bring together the best minds and resources possible toward bringing new drugs to market to benefit patients, faster. 

MJFF:  Why is repositioning such an attractive option for companies?

DF: Most drug candidates fail long before they ever make it to clinical testing.  But if you can begin with a drug that has at least been shown to be safe in human beings, and that might have some potential to treat a certain disease, there’s a much lower risk to investing in its ongoing development.  

In any sector, but especially in central nervous system (CNS) disorders, having data on how a drug works in human beings will always trump pre-clinical work—just because a drug has been shown to be effective in a lab, doesn’t at all mean it will work in people.  We will probably continue to fail frequently with repositioned drugs in the second phase of clinical testing (when we begin to learn about a drug’s efficacy), but if we can eliminate all of those early steps to get to this second phase, we can save a lot of time, and money. 

In short, by starting further along the pipeline, drug companies will hopefully be able to develop more drugs for the patients that need them, and faster. 

MJFF: What roles can disease foundations such as ours play in continuing to support the pharmaceutical industry?

DF: MJFF, for one, has been ahead of the curve. Pharmaceutical companies have to make decisions that quite frankly have to balance the high risks with the potential return on the investment.  But foundations can help to de-risk particularly interesting leads that might not otherwise get the attention they deserve. One way that MJFF is doing just this is through repositioning—by supporting trials into existing drugs that look interesting for PD, but that, without their help, might not ever get off the ground.