The first law of new drugs: new drugs with the same mechanism cannot compete with generic drugs. The second law of new drugs: first in class always wins in the competition with me too / better new drugs. The Matthew effect of the first new drug makes it dominant in the competition. The third law of new drugs: the law of risk conservation of new drugs.
IMS forecasts that the global prescription drug market will reach US $1.3 trillion in 2018, and the world is becoming more and more affluent and aging at the same time. These two factors contribute to the amazing potential of the new drug market.
However, the development of new drugs is facing unprecedented challenges. According to the data provided by tufts Research Institute, the average cost of discovering a new drug is an amazing 2.6 billion dollars.
This is a rapidly changing world, and traditional new drug models are increasingly challenged. If we don't see the future trend and adhere to the eliminated new drug model, it is undoubtedly a dilemma for the characteristics of "three high and one long" new drugs. Therefore, how to find new drugs and share the market of 1.3 trillion US dollars has become a key problem for all pharmaceutical companies.
Three new drug development models
In summary, there are about three modes of new drug research and development: the first in class mode, which is the so-called first in class mode; the fast tracking new drug mode, which obtains the drugs of me too, me better and best in class; and the me only mode, which can be understood as a unique new drug mode for clinical unmet needs.
The first new drug model has high requirements for pharmaceutical enterprises. Most of the projects are based on the progress of basic science. This model is competitive, but the enterprises with insufficient experience and weak strength are easy to be treated as me too. The fundamental reason why big pharmaceutical companies rush to make the first new drugs is the Matthew effect caused by the top advantage of the first new drugs in the market. But the model is not suitable for Chinese companies.
For the rapid tracking new drug model, they are all tracking new drug research for the first new drug. In fact, there is no difference between me too, me better or me word, but it is difficult to find living space in the gap of the first new drug. The best in class is a black swan event that can't be met. Only when the first new drug has major defects and can't meet the basic clinical needs, can powerful companies have a chance to find it.
The fast tracking new drug model has a strong demand for timeliness. There is a certain opportunity for me too / better, which is 3 years from the initial new drug's listing, but it still faces the suppression of Matthew effect of the initial new drug. After 5 years of the initial new drug's listing, there is basically no opportunity for me too / better. When its sales do not reach the peak, it is terminated by the generic drugs of the initial new drug. Most of the new drugs of me too / better / worse from Chinese companies are more than 10 years behind the first innovative drug.
Compared with the first new drug, many companies regard pre clinical and clinical data as a me better, in fact, there are more and more cases of such me better being eliminated after being put on the market. Of course, if you really have the ability to see the loopholes of the first drugs, find out the optimization methods, evaluation methods and clinical development methods to make up these loopholes, and dare to invest a lot of money to expand the clinical use of the target mechanism, then the best in class can be a very effective R & D strategy.
Of course, me too can be the best in class. No one can guarantee that the first one is the best. But from the perspective of R & D, it is more difficult to find a better follow-up drug with clinical effect than the first drug than most R & D enterprises can imagine. If the initial drug has obvious defects such as short half-life and too large dose, the original company will definitely follow up the drug to solve these problems, and the original company is most qualified to solve these problems, basically less than other companies.
What's the me only model? Me only is a special first in class, but it is different from the first in class project in quality. Ordinary first in class is easy to be me too, but me only is not. Me only has chosen a non competitive field to meet the clinical unmet needs. This model needs more project research work to determine its me only status. Although it is difficult to project, due to no competition, its market risk in the later stage is very small.
There are several ways to achieve me only: first, the structure-activity relationship of drugs is very strict, "there is only one store.". For example, the lithium salt used for depression, the closest sodium salt to it, has no other therapeutic effect except for hypertension. Clopidogrel and oxazolidinone are also in this category; the second is that the optimization route is not widely known. If you have an exclusive animal model to screen active compounds, then competitors don't know how to continue to optimize your first drugs. Many drugs, such as dimethyl fumarate, pirfenidone and ketamine, can be classified as this type; the third way is that the mechanism is unknown. Now the mainstream mode is target centered, but this mode has a big disadvantage, that is, it is very easy to be tracked and surpassed by competitors. The more successful case is clozapine. You only know that the drug works well, but you don't know why.
Due to the small molecular size of EMI's Dimethyl Fumarate, I don't know how to continue to optimize it, so it's not easy to be me too, and it's difficult to have similar competitive products in the future, so it's a me only project. This product was previously approved for anti psoriasis in Germany, and most pharmaceutical chemists don't think it can be used as a drug, but bageni has given this very small molecule new life. In 2013, it was approved as the third oral drug for multiple sclerosis in the United States. At present, the mechanism of dimethyl fumarate is still unclear, but its efficacy and safety are more competitive than other oral or injection drugs, and it is more effective than complex biomacromolecules in the treatment of multiple sclerosis. Analysts predict sales of the drug will exceed $6 billion in 2019.
Pirafenidone is also a me only project. It is a small molecular compound synthesized in the 1970s, and it was initially found that it has anti-inflammatory effect. In 1994, it was applied by Solomon magolin of the United States for patents related to synthesis, inhibition of fibrosis, etc. and registered with deskar, the trade name of marnae company, as the test drug.
In 1995, pirfenidone was found to improve pulmonary fibrosis induced by bleomycin and cyclophosphamide. Subsequently, more and more animal experiments confirmed that it can inhibit the fibrosis of lung, liver, kidney and other tissues.
In October 2008, pifenidone was applied by yannoyi pharmaceutical and first approved for marketing in Japan, becoming the first drug approved for treatment of idiopathic pulmonary fibrosis in the world. The structure of pirfenidone is simple, because I do not know how to continue to optimize it, so it is difficult to be me too.