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505(b)(2): Repositioning, Repurposing or What?

Last week I made a presentation at the Society of Biomolecular Sciences (SBS) 2010 Annual Meeting in Phoenix (due to the Iceland volcano eruption, many participants are still there).  The occasion was the inaugural meeting of the newly formed Special Interest Group for Repositioning Drugs (see the announcement of this new SIG). Dr. Chris Lipinsky was also on the agenda. Chris is a consultant to Melior Discovery and he is widely viewed to be a founding father of drug repositioning while at Pfizer. He and I have appeared at previous conferences on drug repositioning sponsored in part by Melior and Camargo. Judging from the name of the organization, and looking at Chris’ background, you might ask why was Camargo and Ken Phelps asked to present.

After all, the subject of SBS is, in large part, about using screening techniques to aid drug discovery. Repositioning, as defined by Chris and others is the process of examining alternate indications for drugs that have failed in the clinic. We have also heard that repurposing (with or without the hyphen; re-purposing) is interchangeable with repositioning. When many people think of repositioning drugs they expect the outcome to be new IP and a full NDA. Pharma does repositioning as a way to salvage a drug that was in its pipeline. But as Chris pointed out in his fine talk, repositioning in pharma can also be used to extend the life of an approved drug. This is where I came in.
Camargo specializes in helping its clients make changes to drug products that are already on the market. Since there is often publicly available pre-clinical and clinical information to support the existing product and the proposed changes, Camargo uses the 505(b)(2) regulatory pathway to gain approval. The changes we make are also very much applicable to pharma ‘repositioning’. I cited a couple of examples:

It is well established that the efficacy of many existing drugs are less than optimal. In fact, new drugs often fail in phase 3 because they don’t show superiority to placebo. The following figure shows that, for many classes of drugs, less than 50% of patients find them effective.

Why aren’t a greater percentage of currently marketed more effective ? While there are many reasons, sometimes it is the dose, site of administration or formulation. Many of these drugs can be improved – “repositioned” by making the required changes.

For many drugs, lack of efficacy may also be related to the time of dose as shown in the following slide.

To address the timing of a dose, it may be possible to design an appropriate formulation.

At SBS, I used the example of prodrugs. Prodrugs are modifications of new or existing drugs to improve efficacy or safety. Prodrugs can be developed to improve bioavailability, for example, to change an IV to oral administration. Oral delivery may reduce side effects and allow higher doses.

In summary, drug repositioning or repurposing can be performed on both pipeline and currently marketed drugs. 505(b)(2) can be used to gain approval of the repositioned or repurposed marketed drugs.