The number of drug approvals has been decreasing in recent years, which is mainly because of the unexpected side effects in clinical trials and lack of sufficient pharmacokinetics in humans. There is a major difference in pharmacokinetics between humans and animals after all, and it seems unavoidable to some extent that highly safe and excellent pharmacokinetics in animals may not necessarily be found in humans (limitation of conventional developmental strategy of pharmaceuticals). To solve this problem, a new drug discovery strategy is required (the paradigm shift of drug discovery strategy) with keywords of low cost and safety.
With the appearance of antibody drugs, the price of pharmaceuticals has been rising sharply, which has emerged as a social problem. So far, drugs had been considered sellable products even at a high price: however, in recent years, the need for low-cost pharmaceuticals has increased. This is because no economic growth as has thus far been provided will be expected in developed countries, such as Japan, and it is necessary to reduce the drug cost due to increased medical expenses in an aging society.
On the other hand, one of the reasons for the stagnation of new pharmaceutical development is the tightened approval process for pharmaceuticals, in particular, especially higher safety requirements, and how to secure safety becomes more important.
Under these conditions, we are promoting drug re-positioning (DR) as a new drug strategy. DR is to discover new pharmacological effects of drugs sufficiently confirmed in terms of safety and pharmacokinetics in humans (drugs already approved as therapeutic agents for some diseases) and to develop them as therapeutic agents for other diseases (additional indications).
Although additional indications have been approved so far, those are based on effects identified by accident in clinical use or limited to cases where pharmaceutical companies expanded indications of their own products for similar diseases. Unlike these cases, we are promoting comprehensive, systematic, and scientific DR. To be more precise, we establish our own library of approved drugs that lists only drugs commercially available in Japan (approved drugs), detect drugs containing targeted pharmacological effects (for example, anti-tumor effect) by screening, and confirm these effects in clinical trials. Under these conditions, we are promoting drug re-positioning (DR) as a new drug strategy. DR is to discover new pharmacological effects of drugs sufficiently confirmed in terms of safety and pharmacokinetics in humans (drugs already approved as therapeutic agents for some diseases) and to develop them as therapeutic agents for other diseases (additional indications).
As the scientific background to DR, it is difficult to consider that a low-molecular compound can act on only one of numerous proteins in cells, which can indicate that approved drugs may act on multiple in vivo molecules and may have multiple pharmacological effects.
For example, non-steroidal anti-inflammatory drugs (NSAIDs) have anti-inflammatory effects through inhibitory effect on cyclooxygenase (COX). In recent years, multiple target molecules of NSAIDs, other than COX, have been identified, and they are reported to be related to antitumor or other effects of NSAIDs.
As another scientific background of DR, it has been elucidated that the underlying cause is common in multiple diseases, which had been considered absolutely unrelated to each other. For example, chronic inflammation is involved in any of cancer, Alzheimer's disease, and diabetes. This indicates that an approved drug for some diseases can be expected to be effective in a different disease, if they have the same underlying cause.
The first merit of DR is reduced risk of unsuccessful development because safety and pharmacokinetics in humans are already well known, and unexpected side effects, which means a higher possibility of successful pharmaceutical development.
Furthermore, the use of existing data (for example, in vitro toxicological studies, toxicological studies or ADME studies in animals, phase I clinical trials) allows you to reduce time and costs for development.
As one of the reasons for stagnation of new pharmaceutical development, efficacy observed in animals may not necessarily be obtained in humans. This is due to limitation of animal models, and it is especially difficult to evaluate efficacy of pharmaceuticals with animal models in mental diseases (for example, depression) and sensory symptoms (for example, pain).
For these diseases, a candidate drug should be administered to patients at first (early and exploratory clinical trial). Then, actual pharmaceutical development can be initiated, only when the pharmacological effect is identified in the trial, which can increase the possibility of successful pharmaceutical development significantly. Aside from new compounds, this strategy can be applied for approved drugs in which the safety has already been secured. This is one merit of DR.
As shown above, DR is an excellent method to realize quick, low-cost and highly successful pharmaceutical development, and we promote the business to expand this method.
Unfortunately, Japan has lagged behind Europe and the United States in DR. For example, in the United States, a study meeting concerning DR, called the DR summit, was held yearly for four years since 2006, and bio-venture companies and mega pharmaceuticals gathered from the country and Europe; however, we were the only company from Japan that attended this meeting.
In Europe and the United States, mega pharmaceuticals have changed rapidly their drug discovery strategy to DR from around 2007. DR became popular in Europe and the United States earlier, as new strategies for drug discovery, such as genomic drug discovery also was initiated, and its limitation was recognized in these areas prior to Japan. Actually, successful results with DR are reported continuously in Europe and the United States.
On the other hand, the strategy shift to DR has been delayed in Japan. The government and companies paid no attention to DR irrespective of our appeals; however, since a special TV program titled “No drugs developed” produced by NHK was broadcast in March 2010, and our research was introduced as the ice in the hole to solve this problem, attention has come to be focused on DR.
As attention increases on DR, we as a leading company in this field continue to promote DR by establishing the library of approved drugs.
Similar libraries that collect approved drugs are commercially available for a high price of several million yen. Compared to these libraries, we believe that the greatest advantage we can provide under the collaborative development is our experience and know-how for DR.
In case of DR, tasks other than research would often be a bottleneck, including evaluation of screening results, drug manufacturing, patent application, translation to clinical trials, PMDA consultation, strategy for high drug price, or licenses. We hope to help your excellent research results lead to effective new drug development using our experience and know-how.