"Medicine King" Enters The Market Of Medical Insurance And Biological Analogues: Will The Market Of Domestic Rheumatoid Arthritis Usher In An Inflection Point?

Gan Jun photo

In 2018, anti rheumatic drugs were next to the treatment of cancer, with global sales of up to US $58 billion 100 million. But at the same time, the market of biologics for rheumatoid arthritis (RA) is an area with boundless global scenery and almost unknown in China.

In November 28th this year, the national health insurance negotiations were settled by Guan Xuan, the industry's hot debate on the seven year global "drug king" training Miller (adalimumab) game for many years finally entered the medical insurance directory.

Miller has been faced with patent challenges all over the world, and has been playing a new role in patent litigation.

In addition to existing competing products in the medical insurance directory, the State Drug Administration approved the registration of Adalimumab Solution for Injection (brand name: Le Le), a local pharmaceutical company, in the early November before the health insurance negotiations. The drug is the first adalimumab biologically similar drug approved in China, and its indications are autoimmune diseases such as ankylosing spondylitis, rheumatoid arthritis and psoriasis.

China's rheumatoid arthritis patients have about 400-500, is the "rheumatism" big country. However, due to the late entry of biological drugs into the domestic market, high drug prices, low patient visits and lack of training of doctors, the treatment is not ideal.

With the gradual listing of all kinds of new drugs abroad, the adjustment of medical insurance catalogues and the impact of home-made biological analogues, the domestic market for rheumatoid arthritis is ushering in a new turning point.

"Undead cancer"

There are many kinds of arthritis, but the etiology of most arthritis has not yet been identified. According to WHO's national assessment report on aging and health in China, joint inflammatory diseases have become the number one disability in the world. The total number of arthritis patients in the world is 355 million. As of 2015, the number of arthritis patients in China was more than 100 million, and the prevalence rate of arthritis in elderly people aged 60 and above was 25%. The prevalence of female arthritis (30%) was higher than that of males (20%), and urban residents (26.6%) were higher than rural residents (23.1%).

Rheumatoid arthritis is an autoimmune disease characterized by erosive arthritis. It is called "immortal cancer" because of its complexity and danger. It mainly endangers the articular membrane, cartilage tissue and skeleton, resulting in joint damage, pain and deformation. The peak age of the disease is more than 30-50 years old. In China, patients with rheumatoid arthritis also have many characteristics, such as many diseases, long course of disease, and more severe patients.

According to IQVIA data, due to lack of medical resources and disease recognition, more than 30% of RA patients had symptoms for more than 1 years before treatment, which increased the difficulty of treatment. After treatment, the remission rate of many patients is less than 20%, much lower than that of other countries and regions.

Li Sheng Guo, director of Clinical Immunology Center / rheumatology department of Peking University People's Hospital, said, "the listing of biological agents opens up a new prospect for the treatment of rheumatoid arthritis in China. However, the clinical compliance rate of patients in our country is still low, and the clinical remission rate is only 22% after one year treatment.

Traditional oral anti rheumatic drugs (DMARDs), such as non steroidal anti-inflammatory drugs, improving the condition of antirheumatic drugs and glucocorticoids, have limited curative effect and poor tolerance. In 1998, the world's first TNF- alpha inhibitor infliximab was approved to be marketed, opening up the era of biologicals for anti rheumatic drugs. Adalimumab, etanercept, bezalizumab, and gram immu mAb were all TNF- alpha inhibitors. In addition, RA biologics also include JAK inhibitors, monoclonal antibodies against IL-6 and so on.

Adalimumab Solution for Injection is the world's first approved monoclonal antibody against human tumor necrosis factor (TNF-), which can specifically interact with soluble human TNF- knot and block its interaction with TNF receptor p55 and p75 on the cell surface, thus effectively blocking the inflammatory effect of TNF-. In addition, adalimumab may also produce antibody dependent cell-mediated cytotoxicity (ADCC), complement dependent cytotoxicity (CDC), and induce apoptosis by removing TNF- from the cross membrane.

At present, a number of RA biologicals have been approved in China, and indications are diversified. In December 14th, Belgian biopharmaceutical company announced that it was listed in China for its next category of wind biological biological preparation, pzli bead monoclonal antibody (Xi Min), and the first prescription was issued in November 5th at a price of 2457 yuan / branch.

In the case of many competing products and entering into health insurance, a differential competitive strategy was formulated for superior time compared to that of pezlezumab. "Pezlezumab injection is the only inhibitor without Fc fragments and pegylated TNF- inhibitor. There is hardly any placental transport. It is the only biological preparation approved by China for the treatment of rheumatoid arthritis with clinical needs during pregnancy." With the launch of this drug, it has expanded its business in China to the field of immune system diseases.

According to Tian Xinping, director of the Department of Rheumatology and immunology, Peking Union Medical College Hospital, "if the female patients with rheumatoid arthritis do not control the disease, they will not only weaken the function of ovulation, prolong the time of conception, but also increase the risk of many adverse pregnancy outcomes, such as premature delivery, low birth weight and preeclampsia. The rate of postpartum recurrence is very high. It is not only the unsatisfied needs of women in childbearing age, but also an important problem for every rheumatoid immunologists.

Price seesaw warfare

According to EvaluatePharma data, by 2024, anti rheumatic drugs were the third largest market for drug therapy in the world, after cancer and antidiabetic drugs. It is estimated that market sales will drop 1% from 58 billion US dollars in 2018 to US $54 billion 600 million in 2024 and to 4.5% in 2024.

But even if it slipped down, AI Bo Wei still firmly controlled the market of anti rheumatic drugs. EP predicts that by 2024, AI Bo Wei's global sales in the field of anti rheumatism will be $17 billion 406 million, and its share will drop from 33.1% to 30.7%. Followed by Pfizer, accounting for 10.6%; Amgen ranked third in 7.1%; Johnson slipped 9.4%, accounting for 6.9%.

It is estimated that by 2024, the top five anti rheumatic drugs in global sales will be Humira, 15 billion 233 million dollars for repairing Miller, 4 billion 72 million for Enbrel, 2 billion 845 million for Simponi, 2 billion 621 million for Otezla and 2 billion 570 million for Upadacitinib.

Turning to the domestic market, although Miller has been selling rapidly in the world, it has been "depressed and frustrated" in China. The main reason is its high price. The annual average cost of treatment is 200 thousand. In 2018, Miller's global sales amounted to 19 billion 936 million US dollars, an increase of 7.4%, and its sales began in 2003. As of the end of 2018, the total sales revenue of Miller had reached US $132 billion 900 million, but in 2018, its total sales in China amounted to only 5 million 330 thousand US dollars, accounting for 0.02% of the global market.

Unlike the strong commercial insurance system in the US, the RA biologics listed in China are expensive and difficult to enter into medical insurance. The annual cost of the biologics is over 150 thousand yuan, and the utilization rate is much lower than that of the mature markets abroad. As a result, many RA drugs continue to use price cuts as a health insurance negotiation strategy, including Roche Amy, Abe maintenance Miller and so on. In August 2019, it was included in health insurance.

Repair Miller also from a single price of more than 7600 yuan, to this year, the net to take the initiative to cut prices 60% to 3160 yuan, until this year, the national health insurance bureau announced the negotiating price, adalimumab with 1290 yuan / branch won the bid, indications for rheumatoid arthritis, ankylosing spondylitis and psoriasis patients, the agreement period is from January 1, 2020 to December 31, 2021.

Infliximab was also negotiated into the national health insurance directory, and the price was not announced.

In terms of domestic enterprises, in December 13th, Shanghai sunshine medicine purchasing network announced the announcement of new drug insurance negotiations in 2019. The list of bio analogues of the newly approved listed company's biodiesel is not published.

In an interview with the twenty-first Century economic report, Lin Na, a Chinese pharmaceutical industry analyst at UBS Securities, said that for the domestic enterprises that want to transform, the category of "wind trade" is a field worthy of attention. "A part of generic drugs companies have advantages in sales channels, similar channels, and some new drugs can be introduced. It is also not realistic to focus on cancer and start from scratch, and can focus on varieties such as rheumatoid arthritis. These drugs need some team that will really be a market, and foreign companies in the front have not done so. First, drugs are too expensive, and patients' ability to pay is poor. Two, no enterprise seriously trains doctors in Department of Endocrinology. It is a very large and long-term market if we reduce the price by health insurance negotiations and biological analogues. "