Expected sales $9 billion! Can Roche keep Herceptin?

Source: Bio exploration 2017-2-20 introduction: Herceptin, the world's first humanized monoclonal antibody for clinical use, is one of the three best-selling drugs of Roche (acquired Genentech in 2009) In response to the interference of patent cliff, Roche intends to use it in combination with patozumab and docetaxel, so that the annual sales volume is expected to reach 9 billion US dollars Can Roche keep its own market when the competition of breast cancer drugs is increasing? Herceptin, the world's first humanized monoclonal antibody for clinical use, is one of Roche's three best-selling drugs In response to the interference of patent cliff, Roche intends to use it in combination with patozumab and docetaxel, so that the annual sales volume is expected to reach 9 billion US dollars Can Roche keep its own market when the competition of breast cancer drugs is increasing? What is Herceptin? Herceptin (trastuzumab for injection) is the first humanized monoclonal antibody for clinical use It is a molecular targeted therapeutic drug for HER-2-positive breast cancer In the development of breast cancer, the oncogene HER-2 plays an important role in the regulation of cell growth, development and differentiation The abnormality of this gene has become an important index to evaluate the malignant degree and prognosis risk of breast cancer HER-2 gene is proto oncogene, which encodes 185kd transmembrane protein, p185 for short The intracellular part has tyrosine protein kinase activity After binding with ligands, HER2 protein forms heterodimer with other members of HER1, HER3 and HER4 in the family, which makes the tyrosine kinase area in the cytoplasm self phosphorylate and activate signal pathway, including Ras / RAF/ MAPK pathway, P13K / Akt pathway, STAT pathway and PLC pathway can inhibit tumor cell apoptosis, promote tumor cell proliferation, enhance tumor cell invasion, promote tumor angiogenesis and lymphangiogenesis At present, about 20% - 30% of breast cancer has HER-2 positive (gene amplification or overexpression) These patients' tumor cells are more aggressive, prone to early recurrence and metastasis, and their survival period is significantly shortened They are relatively insensitive to endocrine therapy and chemotherapy In the process of the birth of Herceptin, slomon, an oncologist of non Genentech employees, made great contributions, while Genentech almost killed Herceptin In the summer of 1984, Axel Ullrich, a German scientist working at Genentech, discovered the human homologous gene of neu gene and noticed that it was similar to another growth regulatory gene (previously discovered human epidermal growth factor receptor gene her), so he-2 was the newly discovered gene In the summer of 1986, at a seminar at UCLA, Ullrich told the story of HER-2 separation on behalf of gene Tucker, which attracted the attention of Dennis slamon, an oncologist at UCLA In 1988, the immune Department of Genentech successfully produced a mouse antibody capable of binding and inactivating HER-2 Ullrich took several bottles from the first batch of antibodies and sent them to slamon Slamon used this antibody to treat the breast cancer cells with HER-2 overexpression in the culture dish As a result, the cells stopped growing, disappeared and died What's more impressive is that when he injected HER-2 antibody into living mice with tumors, the tumors disappeared This is the perfect result expected by slamon and Ullrich: inhibition of HER-2 works in animal models At this time, slamon and Ullrich have identified three basic elements of cancer targeted therapy: oncogene, cancer specifically activating the oncogene, and drugs specifically targeting it Both expect Genentech to take advantage of this leap to produce new protein drugs that clear the signal of cancer causing gene hyperactivity However, Genentech is losing interest in cancer treatment: only a small number of key scientists enthusiastically support the cancer project, and the company's top executives hope to focus on the development of simpler and more profitable drugs; at that time, many pharmaceutical companies were trying to develop drugs with limited knowledge about the growth mechanism of cancer cells, but these drugs are indistinguishably the same When cancer cells and normal cells were poisoned, all drugs were unexpectedly defeated in clinical trials Genentech was worried that if the investment failed, it would exhaust the company's financial resources and draw lessons from other companies, so Genentech withdrew most of the cancer funds In the case of HER-2, Ullrich left genetic tech exhausted At UCLA, however, slamon was left alone Although he is not an employee of Genentech, he is the most dedicated to support HER-2 research Slamon suffered a lot in Genentech company, but he was determined to go his own way He often flew over from Los Angeles, crouched in the corridor and tried to find anyone interested in his mouse antibody, but most Genentech scientists have lost interest But there is also a small group of scientists who have confidence in him David Botstein, a geneticist graduated from MIT, and Arthur D Levinson, a molecular biologist, are strong supporters of the HER-2 project Slamon and Levinson tried their best to use various resources and relationships to persuade the company to form a small entrepreneurial team to promote the progress of HER-2 project In the summer of 1990, Paul Carter, a member of Genentech, made remarkable achievements He made a completely humanized HER-2 antibody, which can be used in clinical trials at any time The antibody is already a potential drug Team members decided to give a name for the antibody In order to embody the essence of the drug, the name combines the three English words of HER-2, intercept and inhibitor, namely Herceptin Living proof poster in memory of slamon's contribution, in 2008, a film called living proof was released in the United States The film tells the story of slamon developing Herceptin from 1988 to 1996 The fatter and the more expensive it is, the greater the market value of Herceptin has been approved for the treatment of breast cancer and gastric cancer since it was launched in 1998 Only four years later (September 2002), the product was launched in China It is reported that more than 720000 patients worldwide have benefited from the use of Herceptin In China, the cost is about 23000-25000 yuan Generally, the price of first tier cities is higher than that of second tier cities In addition, the dosage of the drug is calculated according to the weight, the fatter it is, the more expensive it is, and more than 300000 yuan is needed for a course of treatment The latest research results also confirmed that the combination of Herceptin and chemotherapy can reduce the risk of tumor recurrence by 52% and the risk of death by 33%; more about 80% of early breast cancer patients are cured after using Herceptin; for late patients, Herceptin can also improve the quality of life and significantly extend the total survival period In 2015, Genentech reported that Herceptin combined with perjeta and docetaxel on the basis of standard chemotherapy can significantly prolong the life of patients with advanced HER-2 positive breast cancer In the face of patent cliff as the third best-selling drug of Roche (acquired Genentech in 2009) (the three best-selling drugs: rituximab, avidin and Herceptin), the annual sales of Herceptin has continued to rise since its listing, and the sales in 2012 has exceeded 6 billion US dollars If Herceptin is used in combination with patozumab and docetaxel, the monthly treatment cost of patients will increase to 6000 US dollars (about 40000 RMB), and their annual sales will exceed 9 billion US dollars However, any new drug cannot escape the fate of patent expiration In 2014, the patents of Herceptin in Europe and Japan expired, and in 2015, the patents expired in the United States, which makes the price reduction of low-cost generic drugs and original research drugs will make the market significantly large, and a large number of unmet market demand will make the market penetration of trastuzumab rapidly increase Mylan and its partner biocon are expected to become the first European company to obtain the approval of Herceptin biosimilars this year; GBI research database shows that there are 1050 breast cancer drugs in different trial stages, 347 of which are first in class Can we keep our own market? Jame Abraham, director of breast oncology program at Cleveland Clinic, said in an interview: it is not a wise way to recommend more expensive combination therapy when most women respond better to Herceptin alone Analysts at mirabaud securities, an investment analysis firm, said that if the use of combination drugs did not meet expectations, it would be good for Herceptin to achieve annual sales of $4.9 billion with cheaper generic drugs entering the market Reference: Roche (rhhby) faces off with itself for $9 billion breast cancer drug business