Original research medicine, generic medicine, biological preparation: mantis catches cicadas, yellow finch is behind?

Source: on February 5, 2015, a wave of new biological preparations of new Kangjie are expected to obtain FDA approval and go to doctors' prescriptions This is bound to disrupt the 2015 pharmaceutical market For the pharmaceutical industry, the past 20 century is a century of small molecule drugs The pharmaceutical industry is thriving by identifying a compound with stable nature and relatively simple structure that can treat a group of patients, apply for patents and make huge profits After 2012, the original research drugs with a total value of $53 billion lost patent protection, and in 2014, another $34 billion will face patent cliff The original research drugs, such as Lipitor and Celebrex, have been tested by the market for a long time, and the curative effect is accurate The patients are very familiar with these life-saving drugs, which is the advantage of the original drugs However, after the patent expires, the market will inevitably be eroded by the generic drugs The generic drugs save high research and development costs and long clinical trials, so they have more advantages in price positioning than the original research drugs After market development, they can even reach To compete with the market share of the original research drug The generic drug Mantis cicada hunting (the original research drug) has become a successful support point for many pharmaceutical enterprises It is becoming more and more difficult in the 21st century to quickly find new drugs to replace the drugs with expired patents Moreover, the generic drug Mantis may have become the target of the Yellow finch This year, many mature and emerging companies are looking for salvation in biotechnology Like other types of drug research and development, the research and development of biological agents is a mixed failure and success But the stable process of research and development of "biological agents" is gradually being established These biological agents are composed of macromolecules, which are hundreds of times larger than traditional drugs, and they are produced in animal cells or microorganisms such as bacteria In 2015, a wave of new biological agents are expected to be approved by the FDA and may go to doctors' prescriptions Humira, a drug for rheumatoid arthritis and related diseases, is bound to disrupt the 2015 pharmaceutical market It was approved in the United States in 2002 and developed by American company abbvie According to the research from evaluatepharma, the sales volume of xiulemei reached 11 billion US dollars in 2013, and it has become a prescription drug with sales volume exceeding that of the world Xiulemei's great success has injected a powerful stimulant into pharmaceutical companies, competing to invest in the research and development of new biological agents (Figure 1) Figure 1 annual sales growth trend of xiulemei data source: in the company's annual report 2015, several kinds of biological agents for treatment of high cholesterol will go to millions of patients, and the traditional treatment has lost the ideal effect on these patients Amgen's drug evolocumab may be the first, followed by the cholesterol drug regeneron of Sanofi and regeneron, and a powerful drug bococizumab in the early stage of development of Sanofi (Table 1) Table 1: data source of the heavyweight biopharmaceuticals that are expected to be approved by the US FDA in 2015: according to the assessment of Damien Conover of Morningstar, an investment research company of the economist, the sales of biopharmaceuticals contributed 22% to the sales of large pharmaceutical companies in 2013 and will reach 32% by 2023 Pharmaceutical companies such as Bristol Myers Squibb, Merck, Lilly and Sanofi, whose core businesses are biological agents, almost rely on the contribution of biological agents for their revenue growth In the United States, more than 100 diseases have been investigated, and as many as 900 biological agents are still under development In the next five years, the new generation of biological agents brought new treatment methods, such as "gene therapy" transmitted by virus, that is, by transferring correction genes to the defective cells of patients, replacing the original abnormal genes, making the cells obtain normal genes In 2013, gene therapy has been tried in China In 2015, glybera, the first gene drug in western countries, will take the lead in treating lpld in Germany It is developed by uniqure, a Dutch pharmaceutical company It is estimated that 1.1 million euros (1.3 million US dollars) will be needed for a course of treatment Pharmaceutical companies are scrambling to take over the gene therapy market Pfizer has established a partnership with sparktherapeutics, a biological company, to provide hemophilia patients with normal genes through gene therapy so that they can produce clotting factors It has been reported that through gene therapy, 10 patients with severe hemophilia B can live for several years Milo biotechnology, another pharmaceutical company, is also developing genetic drugs related to muscular atrophy Leng Schleifer, the boss of regeneron, which has several biological preparations to be approved, points out that the main advantage of genetic drugs lies in their specificity: they only do what they should do and rarely cause side effects, while traditional small molecular drugs often cause various side effects, which also leads to their gradual abandonment At the same time of improving the R & D process, biological agents will gradually move from small arms to common diseases The strategy should be the same as dealing with small arms, breaking down common diseases into various sub diseases, so as to realize the re segmentation of common disease market Biological agents will seize the market of traditional small molecule drugs through its advantages of specificity, pertinence and no side effects In the near future, it is not only the generic drugs that will encroach on the market of traditional patent drugs, but the biological preparations will become the late "yellow finch" in the market of traditional patent drugs and generic drugs However, there are still many problems to be solved before the Yellow finch rises to the top 1 There are many difficulties in the development process, but there are many difficulties in the development of biological agents, and the use methods are also difficult Oral administration may be damaged in the stomach, which must be used for injection, infusion, or inhalation, which may hinder doctors from prescribing under certain circumstances Jos é Carlos Guti é rrez Ramos, a senior scientist at Pfizer, said that the way genetic drugs are delivered to the body will continue to improve, so that one day biological agents will be as easy to obtain as tablets The advent of biological agents, just like the emergence of other kinds of drugs, can not be smooth sailing Shares of Roche, a Swiss pharmaceutical giant, fell sharply on December 19, when Roche released disappointing results from two biological agents, kadcyla and perjeta, that were used in combination for cancer patients In addition, the National Institute of health and clinical optimization (NICE) stated that kadcyla's cost for a course of treatment is about US $140000, which is beyond the price range of cancer drugs stipulated by nice, so it is difficult for medical insurance to bear the high price drugs for breast cancer treatment 2 The market development is deeply influenced by the price Like all new drugs, biological agents not only have the problem of PK with the current drugs, but also have the problem of whether patients can afford it For patients who need long-term medication for rheumatoid arthritis, the cost per person per year is as high as $12000, while the cost of Humira is much higher For developed countries, the medical system cannot afford to pay such a high cost of medicine, let alone poor countries With the increase of market share of biological agents, their price and efficacy will be under strict supervision Take Lucentis and Avastin, two biological agents sold by Roche and Novartis for the treatment of cancer and macular degeneration Although the Italian and French governments have found that Avastin can cause blindness, the Italian and French governments have approved Avastin for the treatment of macular degeneration, because the price of Avastin is far lower than that of Lucentis In this case, the adoption of Avastin will save France's medical service system $273 million a year compared with the adoption of expensive Lucentis, according to a French lawmaker This is a very helpless thing for pharmaceutical manufacturers Lucentis went public two years later than Avastin, but its sales growth slowed down gradually, I'm afraid it has nothing to do with its high price (Figure 2) Figure 2 data source of annual sales growth trend of Avastin and Lucentis: annual report of the company 3 R & D costs are getting higher and higher When the patent of traditional drugs expires, other companies can start to sell generic drugs with the same ingredients freely; similarly, when the manufacturer of biological agents loses the patent protection, the rival companies can develop equivalent biological drugs, which is known as“ Biosimilars " However, it is more difficult to develop biosimilars than traditional drugs As its name suggests, biosimilars are similar to, rather than the same as, generic drugs: they can be worse or better, says Ben Perkins of ey, a consultancy In the United States, the lack of clear regulations related to the approval of biosimilars has slowed down the development of the biosimilars market However, things are beginning to change: Apotex, a Canadian company, said in December that the US FDA has considered its biosimilars, a neulasta imitation Neulasta is produced by Amgen, an American company, to help cancer patients resist infection Rand, a research and development firm, speculated on how FDA regulations would evolve, noting that, based on the current situation, biosimilars would save the U.S health system $44 billion over the next 10 years This is a good number However, compared with the cost savings of traditional drug imitations, the total cost savings of bio imitations are not so exaggerated Because the cost of R & D and production of the first biosimilars is very high; the second is that biosimilars are different replicas, and doctors and patients may be slow to accept them, so it is difficult for biosimilars to develop and issue the generic drugs in a short time even if the patent expires, and the cost of research and development is not lower than that of new drugs All of this is good news for companies that have successfully developed Biopharmaceutics, because they are allowed to continue to sell Biopharmaceutics for a long time at high prices They may face a sharp drop in revenue due to patent expiration, but in fact, the "patent cliff" There is no steepness of traditional medicine, and there is almost no worry about it Therefore, after the research and development process of biological preparations, it will gradually go out of the small market, and then according to its specificity, it will nibble the traditional medicine market The mantis catches the cicada and the Yellow finch is behind The traditional medicine has both the threat from the generic medicine and the market pressure brought by the Yellow Finch, the biological preparation.