How repurposing drugs has become an industry in its own right.
NOT long ago, second medical uses of approved drugs were more likely to be discovered by chance than by design. More recently however, due to the finite number of biological targets, and greater understanding of how active pharmaceutical agents are effective, repurposing drugs has become an industry in its own right. AI systems are also playing an increasingly important role in assisting with the discovery and development of repurposed drugs.
During the pandemic, while some claims associated with their use remain unsubstantiated, pre-existing drugs such as dexamethasone and remdesivir have been administered to Covid patients in an attempt to reduce the number of hospitalisations and deaths. Many other trials are currently underway to find out if other known anti-viral or immune boosting drugs could be effective in the treatment of patients with the disease.
A report published by the European Medicines Agency (EMA) has revealed that a total of 97 medicines were recommended for approval by the regulator in 2020 and of these, just 39 were for new active substances. This indicates that well over half were pre-existing compounds that had been repurposed in some way, for example, by restricting their use to a defined patient group or by using them to treat a different disease.
While this is strong evidence in itself of the prevalence of repurposing activity, it is only by comparing the EMA’s data over the past three years that the full picture is visible. For example, in 2018, a total of 84 medicines were recommended for approval and 42 of those were for new active substances. Based on a comparison of the data from 2018 and 2020, the proportion of repurposed medicines recommended for approval by the EMA has risen from 50% to almost 60%.
Closer analysis of the medicines listed in the 2020 report finds that some of the drugs which have received approval for new uses include nitisinone, baricitinib and sucroferric oxyhydroxide. Nitisinone, sold under the brand name Orfadin, has been approved for the treatment of alkaptonuria in adults, whereas it had previously been given approval in 2005 for use in treating the hereditary disease, tyrosinemia. Interestingly, nitisinone was initially developed as a weedkiller with its therapeutic potential being discovered accidentally. Another drug finding a new indication was baricitinib, sold under the brand name Olumiant, that was approved for the treatment of atopic dermatitis oreczema. This is in addition to the original approval of baricitinib in 2017 for treating rheumatoid arthritis.
There are a variety of reasons why the industry has become more focused on repurposing existing drugs. First and foremost, most biological targets and receptors have already been targeted, so it has become more difficult to come up with something new. By comparison, repurposing existing drugs, which already have marketing and regulatory approval for the treatment of a specific disease, is potentially a much easier task. Of course, advances in the use of AI systems have had a role to play in encouraging repurposing activity as it has become much easier to process vast amounts of clinical trial and other patient data in order to identify potential second medical uses for a pre-existing drug or to demonstrate higher levels of efficacy in a more targeted patient group.
The most commonly cited example of a repurposed drug is Viagra or sildenafil, which was originally developed in the 1990s as an anti-anginal drug, although it was later found to be effective in the treatment of erectile dysfunction. Possibly inspired by Pfizer’s discovery, many big pharma companies have since revisited their own back catalogues in search of something with similar repurposing potential. The commercial value of a repurposed drug will be dependent on the size of the new therapeutic group, as well as on its relative effectiveness compared to the drug treatments already available. In view of this, companies generally focus on areas where the therapeutic group is large and where there are no highly-effective treatments currently available.
In many instances, the enhanced processing power of bespoke AI systems, which is often rooted in innovative algorithms and other intellectual property, is retained as a "trade secret". Pharma companies often prefer to take this approach rather than seeking patent protection because the nature of these innovations means they are hidden in the back end of the systems they are using. As such, there is less risk of them being copied. However, in an increasingly competitive market, this strategy could backfire and companies should seek professional advice about the best strategies to protect their innovations.
Some companies are seeking patent protection for certain processing technologies. Often such protection is used to protect the processing technologies used in the manufacture of their key products – for example, the conditions for growing certain cell lines to increase the yield of a specific biological product, or the process for purifying a certain product in an effective manner. In such situations, pharma companies benefit from an extra layer of commercial protection, should their original patented technology for the treatment itself expire or be found to be invalid. A particular example of this is for the biological drug etanercept, sold under the brand name Enbrel. The patent coverage for this drug was extended by protecting a method of ensuring the protein folded correctly during its manufacture, thereby optimising its effectiveness.
With the effects of the Covid-19 pandemic still being felt in many countries around the world, it seems likely that repurposing activity will continue to gain momentum in the months and years to come. There are many repurposing trials underway currently to test the efficacy of existing treatments. Even when existing drugs have proven their safety and efficacy and secured marketing and regulatory approval for the treatment of patients with Covid-19, subsequent developments and the necessary associated clinical trials are likely to be needed. For example, modifications to current approved vaccines are likely to be necessary to take account of new strains of the virus, as well as clinical trials with patients in different age groups and with different underlying biological conditions.
Despite the obvious value of repurposed drugs to society, a recent decision at the Court of Justice of the European Union (CJEU) regarding the use of Supplementary Protection Certificates (SPCs), has disappointed pharma companies and IP professionals alike. In the case known as Santen, a ruling by the CJEU in the summer of last year has significantly reduced the eligibility of products for SPCs, which are intended to help compensate pharma companies for their investment in R&D to develop much-needed drugs. In particular, companies cannot secure additional protection (up to a maximum of five years) for repurposed drugs beyond the typical 20-year patent term. This is in contrast to new drugs, which are marketed under a first regulatory approval. There are concerns that this decision could discourage investment in this vital area of R&D, as the cost of conducting the necessary clinical trials before bringing repurposed drugs to market is often no different than for a new drug.
The practice of repurposing drugs has only recently started to demonstrate its true value. The Covid-19 pandemic has shone a light on the role of drug developers in creating life-saving treatments for patients around the world. The opportunity to create new and effective treatments for some of the world’s most feared diseases, by spotting patterns in vast quantities of data and investing to bring repurposed drugs to market, can’t be ignored.
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