The declining number of new drugs approved each year has long been one of the causes of major concern for pharmaceutical companies. Despite the drastic increase in R&D expenditures during the last decade and the introduction of promising advancements such as high throughput techniques, attrition rates (the percentage of compounds that fail to reach the market) during the drug development process are worryingly high. Such low R&D productivity supposes a hazard for both the pharmaceutical sector and, eventually, patients that urgently require new products to treat their illnesses.

As Nobel Laureate James W. Black once said, “the most fruitful basis for the discovery of a new drug is to start with an old drug”. Accordingly, drug repositioning, or the use of already existing compounds (“old drugs”) to treat diseases other than those originally intended, is increasingly becoming an attractive alternative to de novo drug development. Indeed, getting a repositioned drug to the market is considerably easier and less cost-intensive than developing a new chemical or biological entity from scratch. As shown in the figure below, this strategy increases the probability of success, drastically reduces R&D time and accelerates regulatory approval. Drug repositioning allows companies to bypass several stages of the drug development, since drug candidates have frequently undergone exhaustive testing before being approved for their original indication (see figure below).

scheme-de-novo

The advantages of applying existing drugs to new indications are clear, but you might be wondering, how  is this strategy effectively applied? In some cases, it is only a matter of luck: serendipitous observations led to changing the indication of sildenafil (the molecule in Viagra) from angina to erectile dysfunction. But pharmaceutical companies cannot rely on luck to create a strong portfolio, and that is why more directed approaches have been devised. Broadly speaking, they can be divided into two categories: heuristic or ‘brute force’ methods, which attempt to identify new indications for a library of compounds by “trial and error”; and rational methods, which make educated guesses based on the available knowledge about a compound. Unfortunately, both have limitations: the first is too time- and cost-consuming, whereas the second is inherently slow and can easily overlook not-too-evident properties of the compounds under study.

Anaxomics’s systems biology-based approach, however, provides a new perspective for drug repositioning that combines the best from both worlds while overcoming their limitations. On one hand, it can simultaneously analyse thousands of compounds at a very low cost compared to in vitro or in vivo experiments. On the other, it considers all the available information about diseases and drugs and puts it in the context of human physiology, achieving a holistic understanding of the problem under study.

Two versions of the service are offered: drug-oriented and disease-oriented repositioning. This is to say, we can focus on a disease and identify drugs that could be useful for it or, in the other way around, we can test a compound to reveal potential indications that were previously unsuspected. In either case, we make use of our proprietary TPMS technology (about which you have  probably read in our previous entry) to reach a conclusion in the four steps depicted in the figure below. For those of you who do not entirely trust computerized predictions, rest assured: a team of seasoned experts reviews all the results, making sure they make sense from both biological and commercial perspectives.

drug-repositioning-2 We proud ourselves on reaching a 75% success rate in our assessments, as shown by experimental validation conducted by external research teams. As a matter of fact, using this approach, we have patented drugs or combinations of drugs for treating amyotrophic lateral sclerosis (ALS), glaucoma and Alzheimer’s disease (AD) that have shown promising results in preclinical models. Drug repositioning opens a new horizon of opportunities for pharmaceutical companies, regardless of their size. For small and medium enterprises, failure is no longer a disaster; for big players, it is an excellent way to capitalize on their out-of-patent and failed assets. Also, both academic and clinical researchers have approached us in the past to accelerate their discoveries and boost their publication capabilities. Whichever is your case, even if you are just a little curious, we invite you to contact us for more information about our systems biology-based approach to drug repositioning. Stay tuned for more!

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