Text | Photos
It is a woman's nature to love beauty, which has given birth to a trillion-dollar medical beauty track.
Under the long-term market education, people's demand for medical aesthetics is also constantly changing: from the initial surgery, it has gradually evolved into injection-based micro-plastic surgery. In this evolutionary trend, "face slimming injections" with botulinum toxin as the main raw material have sprung up, and their excellent wrinkle removal and face slimming effects are comparable to "biological scalpels".
How did botulinum toxin, which contains highly toxic poison, become a "biological scalpel"? What kind of industrial pattern will this track usher in in the future?
01 The most beautiful poison
Botulinum toxin, a formidable name, suggests that the substance is indeed toxic, and it was first discovered as a poison.
One day in the 20s of the 19th century, in a small town in Germany, a strange disease suddenly appeared, a large number of residents suddenly experienced pain, fatigue, and even muscle tremors, paralysis and other symptoms after eating a sausage. Later, a doctor named Justinus Kerner discovered that the patient was poisoned because the sausages he ate had been stored for too long and produced a toxin, which he named "botulinum toxin" (Latin - botulus for sausage).
However, the accident did not go unnoticed, and in 1897 the same accident was repeated in Belgium, where 34 residents died of poisoning from eating expired canned ham. During the investigation of the accident, Belgian bacteriologist Professor Emile van Ermengem isolated a new microorganism from the canned ham and named it Clostridium botulinum. Scientists have repeatedly confirmed that Clostridium botulinum toxin produces a bacterial exotoxin, known as botulinum toxin, during the process of growth and reproduction. As the most potent toxin known at the time, Clostridium botulinum was 10,000 times more toxic than potassium cyanide. Due to the strong toxicity of botulinum toxin, during the Second World War, botulinum toxin became one of the important options for biological and chemical weapons, becoming a veritable deadly toxin.
However, there are two sides to everything. On the other hand, poison that kills people can also become an antidote to the sick and save people if it is used properly.
In 1978, Allen Scott, an American ophthalmologist, discovered the medical value of botulinum toxin for the first time, and he tried to use the diluted toxin to block the release of acetylcholine, and use the properties of paralyzing motor nerves and autonomic nerves, and then applied botulinum toxin to the treatment of ophthalmic diseases.
With the advancement of botulinum toxin ophthalmology clinical trials, doctors began to try to apply it to more clinical programs, such as facial muscle twitching, spastic torticollis, limb dystonia and other conditions, and achieved good results. It is these clinical validations that helped Botulinum Toxin Type A (Botox BOTOX) become the world's first approved microbial toxin drug, which was approved by the FDA in December 1989.
However, this is only a small test of the application of botulinum toxin, what really makes botulinum toxin popular all over the world is its application in the field of beauty.
In 1986, when Jean Carruthers, a Canadian professor of ophthalmology, used botulinum toxin to treat blepharospasm, she accidentally discovered that it actually had skin wrinkle removal properties, and her husband happened to be a professor of dermatology, so the couple decided to introduce botulinum toxin into the beauty field. At first, the research was only for glabellar lines, but later expanded to the treatment of crow's feet and forehead lines, and all of them achieved satisfactory results.
Figure: Botulinum toxin beauty principle, source: Guosheng Securities
After a long period of clinical verification, the FDA finally officially approved the extension application of Botox in aesthetic indications in April 2002, and under the promotion of Hollywood stars, it quickly set off a boom in light medical aesthetics.
Today, botulinum toxin has been approved in more than 80 countries around the world, applied to 29 indications, generated more than 28 million research literature, and is injected by tens of millions of people every year, and the global market size has exceeded 10 billion US dollars.
02 History of Fallen Lands in Japan
China's botulinum toxin industry definitely belongs to getting up early in the morning and catching up late.
The earliest application history of botulinum toxin in China can be traced back to 1993, when Lanzhou Bio's Hengli was approved for marketing in China, becoming the first botulinum toxin product to be marketed. Two years after Hengli's listing, Botox officially entered the domestic market. In contrast, South Korea, a "major country in medical aesthetics", did not approve the listing of Botox until 1998, and it can be said that China's botulinum toxin market, whether domestic or imported, was ahead of South Korea in its initial stage.
Although it started early, botulinum toxin products have always been strictly regulated in mainland China due to strong neurotoxicity. It takes at least about 10 years from project approval to final approval, and even if the certified products are directly introduced from overseas, they still need to go through about six years of clinical verification, and the approval threshold is comparable to that of innovative drugs.
The relatively conservative approval attitude has slowed down the domestic development of botulinum toxin products. Botox was only approved for use in the field of medical aesthetics after 14 years in China, and Hengli was only officially approved for the treatment of frown lines in 2012. Until 2020, only these two botulinum toxin products have been approved in the domestic market. Focusing on the market at that time, Hengli was 3 times the sales volume of Botox, but due to the lower price of Hengli, the sales volume was slightly lower than Botox.
In contrast, in the Korean market, Botox and Hengli were approved in 2004 and 2005 respectively for the treatment of frown lines. The local botulinum toxin brands in South Korea were only approved after 2006. However, due to the extremely high acceptance of national medical aesthetics and relatively relaxed supervision, Korean brands soon gave birth to popular products such as Medytoxin (pink poison), Botulax (white poison), Nabota (green poison), and it was during this time period that Korean botulinum toxin achieved corner overtaking.
Since the second half of 2020, China's botulinum toxin market has begun to explode, with the successive approvals of the UK's Ipsen and South Korea's Hugel, the number of domestic compliant botulinum toxin products has increased to 4, and the competition pattern has become more intense. From 2021 to 2023, the market size of China's compliant botulinum toxin will be 4.6 billion, 6.5 billion and 8.1 billion respectively, with an annualized compound growth rate of 33%.
In February this year, Xeomin (West Malaysia), a botulinum toxin brand under Merz Pharma of Germany, was approved for marketing in China, increasing the number of botulinum toxin approved in China to 5. With the increasing demand for beauty, the botulinum toxin market is gradually penetrating from first-tier cities to second-tier cities, and it is estimated that by 2030, China's compliant botulinum toxin market is expected to reach 39 billion yuan.
Figure: List of domestic medical beauty botulinum toxin products, source: Tianfeng Securities
Although the botulinum toxin market has great room for growth and the industry prospects are considerable, it still needs to face the impact of "parallel imports". Since most of the botulinum toxin products in mainland China are imported from overseas, consumers have formed a deep-rooted idea of "flattering foreigners", which makes the domestic botulinum toxin market full of a large number of "parallel imports".
According to the data provided by the China Plastic Surgery Association, in 2019, 70% of botulinum toxin products sold in the domestic market were composed of fakes and parallel goods, the price ranged from 1/10 to 1/2 of the genuine products, and the actual annual consumption was about 5 times that of regular products. Although the proportion of formal products has only increased after 2020, parallel imports still account for more than 50%. "Parallel imports" have brought great safety hazards and caused chaos in the medical cosmetology industry.
In the face of the chaos of medical cosmetology, since 2021, the relevant national supervision and management departments have "struck hard" and actively issued various relevant documents to expand the scope of supervision and strengthen supervision, the development of the medical cosmetology industry has moved from rectification to compliance development, and the scale of the regular botulinum toxin market will also usher in more rapid growth.
03 The Red Sea competition is about to begin
With the rapid popularity of the medical aesthetic industry, companies are also focusing on the fast-growing "botulinum toxin". Aimeike, Huadong Pharmaceutical, Bloomage Biotech, Fosun Pharma, CMS Pharmaceutical, Haohai Biotech, and Inming Biotech have joined the competition, and the involution of the botulinum toxin track will continue to intensify.
In order to shorten the listing process, most of the major domestic manufacturers have entered the botulinum toxin product market by acting as agents for foreign marketed products: Aimeike chose to act as an agent for Hutox (orange poison) of the Korean company Huons Bio, Huadong Medicine chose to act as an agent for The Toxin (blue poison) of the Korean company Jetema, Fosun Pharma chose to cooperate with the American company Revance, and Haohai Biotech chose to cooperate with the American company Eirion.
Figure: Some botulinum toxin products under development, source: CITIC Securities
Based on the current clinical approval schedule, it is expected that 10 botulinum toxin products will be launched in the next 3-5 years, and the botulinum toxin industry will also enter the second half of the fierce competition.
In this competition, time is naturally a very critical factor, and the logic of innovative drugs is the same, similar products will be launched first will gain the majority of the market share, and the products that are listed later are full of uncertainty, so the products that have been launched at present undoubtedly have a first-mover advantage.
For latecomers, "product power" is the key to victory. The duration of botulinum toxin products currently approved for marketing is about four months after use, which is a relatively short period of time. At the same time, products often contain exogenous/inactive accessory proteins and other clostridia proteins, which pose a certain immunogenicity risk. The development of new botulinum toxin products with longer life, higher purity and higher safety can attract more consumers and gain an advantage over the competition. In addition, the development of new indications is also another development idea for botulinum toxin products to enhance their competitiveness.
The reason why Botox has been on the market for more than 20 years is that it occupies the dominant position in the global botulinum toxin market because of the many indications it has developed. At present, Botox has more than 27 approved indications worldwide, in addition to cosmetic, it can also treat migraine, back pain, as well as hyperhidrosis, eyelid beating, strabismus, etc. Time magazine once compared Botox to a "Swiss Army Knife", which means omnipotent.
Judging from the current research results, medical aesthetics is by no means the ceiling of botulinum toxin, and still has unlimited potential in many fields. More than 100 kinds of diseases have been reported for botulinum toxin treatment at home and abroad, involving multiple disciplines and specialties, and even including depression, rhinitis and other fields.
Time, product power, and indications will be the three key elements of botulinum toxin competition in the second half.