This article is based on an interview, during the interview, the other party asked why the global drug king Humira, with sales of more than 20 billion US dollars in the world, but the sales in China are so low, what is the deep logic behind this? At that time, I was stunned that we could relish the sales of the global drug king Humira, but often forgot why Humira's sales performance in China was far inferior to that of the global market.
01
Humira is what it is
Humira is the trade name for the biological drug "adalimumab", which is a monoclonal antibody drug. Adalimumab binds and inhibits tumor necrosis factor-α (TNF-α). TNF is a protein associated with many inflammatory diseases such as rheumatoid arthritis, psoriasis, Crohn's disease, ulcerative colitis, and other related diseases.
One day in the millennium, Miles White, who had just been Abbott's CEO for only a year, boarded a plane from Chicago to Ludwigshafen, Germany, for one purpose, to basf headquarters to persuade its chairman, Eggert Voscherau, to hand over Knoll to Abbott.
In the end, Abbott got Knoll for $6.9 billion, but the deal was able to broker not only because of White's personal appearance, but also because one of the key "pushers" that were not seen was that the two companies had very different perceptions of the commercial potential of a monoclonal antibody called D2E7.
As the world's first fully human monoclonal antibody drug, D2E7 is the predecessor of Humira, whose main ingredient is "adalimumab", and is also the starting point for Humira to evolve into a global "medicine king".
Before Humira was marketed, the FDA had approved the marketing of two monoclonal antibody drugs. One is called Remicade, developed by Johnson subsidiary Centocor. The other, enbrel, was developed jointly by Amgen and Pfize. The former's antibody sources, 75% are taken from humans, and the remaining 25% are taken from mice that have been genetically edited to achieve humanization, which belongs to human-mouse chimeric products. The latter is a TNF receptor-IgG fusion protein obtained using recombinant DNA technology.
Humele lived up to expectations, successfully obtained approvals in 38 countries in the first year of listing, and its sales reached 1.5 billion US dollars in 2005, strongly interpreting the "blockbuster" crash, and taking advantage of the trend out of the new century "Medicine King" riding the dust of the performance. In 2021, Humira's annual sales have exceeded the $20 billion mark, with cumulative sales exceeding $170 billion.
In early 2013, the year after Humira beat Pfizer's Lipitor topped the global drug sales crown with $9.48 billion, Abbott officially completed the asset split at its peak. The spin-off of the Innovative Drugs division forms a new research-based biopharmaceutical public company, Abbvie. AbbVie took several of the best-selling patented drugs from Abbott, including Humira.
02
Humira global sales
Humira was first approved by the U.S. FDA on December 31, 2002, becoming the world's first fully human anti-tumor necrosis factor-α (TNF-α) monoclonal antibody approved for marketing. In 2004, Humira's global sales reached $1 billion, becoming a "blockbuster" drug. From 2012 to 2020, Humira has topped the global drug sales list for 9 consecutive years, and nearly 20 billion US dollars in sales in 2018 has created a new record for annual sales of drugs in history.
Until 2021, the laurels of the global "medicine king" changed hands, by Pfizer and BioNTech Comirnaty, a co-developed mRNA vaccine, surpassed Humira's $20.837 billion in sales of $36.781 billion, stripping of the explosive demand for vaccines in the context of the COVID-19 pandemic, and Humira's second-place sales still far exceeded that of fourth-ranked Merck K (ranked third with Moderna's COVID-19 vaccine), while Merck's PD1 target's spectral anti-cancer drug K drug sales were $17.186 billion. The crown of "Medicine King" still seems to be well deserved in the context of the COVID-19 epidemic.
03
Humira China sales
Humira was launched in China in 2010 and, 10 years after its listing, has been approved for four indications: rheumatoid arthritis indications, ankylosing spondylitis indications, moderate to severe plaque psoriasis indications, and moderate to severe active Crohn's disease.
According to the PDB database (china pharmaceutical industry information center developed by the drug comprehensive database) comprehensive more than 400 sample hospitals in 22 key cities to buy drugs, it is found that the sales of Humira has not been ideal, in 2015, the sales of key hospitals Humira were 23.85 million yuan, and since then sales have continued to decline for three consecutive years. In 2018, Humira's sales in China's sample public hospitals and sample chain pharmacies were only 21.2 million yuan and 14.6 million yuan, respectively. In 2019, the sales of domestic sample hospitals were only 18.9 million yuan.
In November 2019, adalimumab injection was included in the Medicare catalogue, and the indications included in the Medicare include rheumatoid arthritis, ankylosing spondylitis, and moderate to severe plaque psoriasis. After being included in medical insurance, the payment standard of Humira is 1290 yuan / 40mg / 0.8ml, a decrease of 83.02%. Based on 70% of the medical insurance reimbursement, the patient only needs to pay 387 yuan out of pocket. In 2020, The sales of Humira ushered in a rapid rise, and the sales of sample hospitals reached 70.08 million yuan, an increase of 270.76% over the whole year of 2019.
04
Why can't you reproduce the "Miracle of the Medicine King"
Reason one: The indications are much less than in the United States
In 2010, Humira's treatment of rheumatoid arthritis, ankylosing spondylitis and psoriasis were approved for marketing in China. In the following seven years, only the above three indications were approved in China. After 2017, Humira has approved five new symptoms in China, including moderate to severely active Crohn's disease, non-infectious (intermediate, posterior, and full) uveitis, polyarticular JIA, plaque psoriasis in children, and Crohn's disease in moderately to severely active children.
Since Humira was first approved for the treatment of rheumatoid arthritis in 2002, Humira now covers at least 17 indications including skin, joints, spine and gastrointestinal tract.
Reason two: the pricing is too high
Humira was listed in China in 2010, after listing in China, Humile a needle of 7600 yuan, the first month of 4 injections, it costs nearly 30,000 yuan, after two injections per month, 15200 yuan per month, the annual treatment cost of nearly 200,000 yuan.
Until 2019, the State Food and Drug Administration approved the application for the listing and registration of BAT1406 (trade name: Gloria) of Adalimumab injection developed by BIOTEC. This is the first approved adalimumab biosimilar in China, and the indications are autoimmune diseases such as ankylosing spondylitis, rheumatoid arthritis and psoriasis.
After the emergence of Adamu shou imitation in the Chinese market, Xiu Meile lowered the arrogant head of the "medicine king", and in 2019, AbbVie took the initiative to lower the price of Xiu Mei Le, from 7600 yuan / branch to 3160 yuan / piece, a price reduction of nearly 60%. In November 2019, Humile officially entered the medical insurance directory after the national medical insurance negotiations, and the payment standard of Humile was 1290 yuan / 40mg / 0.8ml, a decrease of up to 59% compared with the last price reduction.
Reason three: it is too late to enter the medical insurance directory
Different from the medical security system in the United States, which is mainly based on commercial insurance, the medical insurance system in the mainland is managed by the National Medical Insurance Bureau, and the medical insurance fund often refuses to be excluded from the list of major illness medical insurance for types such as Humele. Before Humira was included in the medical insurance directory in 2019, only Shenzhen and Qingdao realized the medical insurance reimbursement of Humile, and the high cost of self-care treatment determined that under the mainland's medical insurance system, patients with autoimmune diseases would choose drugs that could be used and afforded. According to media reports, after Shenzhen included Humira in the medical insurance for serious illness, the number of people using Humile increased by nearly 10 times.
Humira may have a global pricing balance in the consideration of the inclusion of medical insurance funds, but under the different medical systems in China and the United States, the stronger payment capacity of American commercial insurance determines that it still has a better market in the United States, and in order to maintain profits in the United States market, it has to strategically choose to abandon the domestic market. If china were to impose low pricing in order to enter the health insurance catalogue, it might have a significant impact on its global sales.
Reason four: the patent expires, and wolves are around
Humira patents expired in the United States, China and Europe in 2016, 2017 and 2018, respectively. Humira has been able to survive for 20 years, and in addition to continuously expanding indications, it has also established a solid patent jungle. It is understood that in the United States, AbbVie filed 247 patent applications related to Humira, of which more than 100 were granted and approved, which far exceeded the number of AbbVie's patent applications in Europe and Japan. Through patent evergreening, the R&D process continues to apply for multiple patents at different points in the drug life cycle, delaying the time to market of generic drugs of Meile in the United States from 2017 to 2023.
The United States, as Humaleus' largest market, has nearly $50 billion in sales in the United States from 2019 to 2021, almost five times AbbVie's sales in Europe in the same period. The dismal sales in the Chinese market doomed the Chinese market not to be the home of Humira, and under China's different medical systems, Humira finally chose the US market as the home, delaying the expiration time of the US market.
Humira's core patent expired in China in 2016, and many mainland enterprises began to lay out adalimumab biosimilars, of which BIOTAI, Haizheng Biologics, Cinda Biologics, Henlius Henlius, and Chia Tai Tianqing all had products approved for listing. In the context of medical insurance negotiations and collection, so many adalimumab markets are destined to become the Red Sea. Even if it enters the medical insurance directory in 2019, in the future, in the medical insurance negotiations and collection, it may still face the dilemma of broad-spectrum anti-cancer drug pd1.
04
Is there still a chance
From the perspective of the timeline, entering the medical insurance directory is the watershed of Humile's strategy in China, before 2019, Humile still maintains high pricing in China due to the need for consistent global pricing, and there is obvious dissatisfaction under China's medical insurance system. Patients in autoimmune diseases do not choose Humira because of its better efficacy, and alternative drugs are still the first choice to ensure a normal life.
With the expiration of the patent, it is foreseeable that not only the Red Sea competition for adalimumab biosimilars in the Chinese market, in 2018, Humira lost patent protection in Europe, at least 6 biosimilars were approved for marketing, and its US patents will also expire in 2023, when at least 9 biosimilars will enter the US market. Evaluate Pharma had predicted that by 2026, Humaleu's global sales would fall to $6.83 billion.
In China, considering the dual pressure of medical insurance negotiations and collection, Humile may be different and optimistic. The former global "medicine king" may not be far from Twilight