Interface News Reporter | Huang Hua
Interface News Editor | Xie Xin
Botulinum toxin is one of the most recognized products in the medical aesthetic industry. In recent years, under the background of domestic substitution and technological iteration, the research of recombinant botulinum toxin is advancing rapidly in China. As a result, a number of companies that are "betting" on recombinant botulinum toxin type A have emerged, and a new round of business war is taking advantage of the wind.
Among them, business strategies that try to occupy both consumer and serious medical care have also emerged. In popular terms, it is hoped that botulinum toxin will be approved not only for cosmetic use, but also for the treatment of diseases.
On June 26, Lin Danhua, clinical medical director of JunHemeng, said in an interview with the media that the company launched the clinical development of recombinant botulinum toxin type A in the serious medical field this year, with the indication of upper limb spasm after adult stroke, and is expected to obtain clinical trial approval (IND approval) in August this year.
Lin Danhua said that from the perspective of global market share, botulinum toxin type A products account for 50% of the market share in the consumer medical and serious medical fields. The application of botulinum toxin products in the serious medical field, such as the treatment of upper limb spasm after stroke in adults, has relatively few approved indications, which is a blue ocean that has not yet been fully developed, and with the continuous progress and development of medical technology, more and more new indications are also being developed. According to the company's research, botulinum toxin type A products have an irreplaceable role in the treatment of upper limb spasm after stroke, and the company is optimistic about the potential of botulinum toxin type A products in the serious medical field, so as to launch clinical layout accordingly and lay the foundation for the development of more serious medical indications.
Botulinum toxin type A products are not new to the general public, but they have been more commonly used in the consumer medical field in the past. The so-called "consumer medicine" field is a medical aesthetic treatment scene that includes the removal of frown lines and crow's feet. At the same time, botulinum toxin, along with collagen and hyaluronic acid, is also known as the "troika of medical beauty".
Corresponding to consumer medical care is serious medical care, that is, the clinical treatment of various diseases. In fact, botulinum toxin products are by no means "beauty-only". It was first indicated by the U.S. Food and Drug Administration in 1989 for strabismus and blepharospasm, which is an injectable drug, and was only extended to glabellar wrinkle removal in 2002. In addition to strabismus, the indications of this product in serious medical fields worldwide include various types of spasticity, spastic cerebral palsy, chronic migraine, overactive bladder, etc.
Since a large number of botulinum toxin products in China were imported products, the understanding that botulinum toxin can be used for disease treatment has also weakened in the business planning of overseas companies to prioritize beauty scenarios.
Of course, JunHe Alliance is also carrying out the development of botulinum toxin type A products in the field of medical aesthetics. At the end of April this year, JunHe announced that its recombinant botulinum toxin type A has completed the phase I clinical trial for adults with moderate to severe glabellar lines as the indication and officially entered the phase II clinical trial. This is the second recombinant botulinum toxin type A to enter the clinical stage in the world. As of the end of June, JunHemeng's recombinant botulinum toxin type A product has completed the enrollment of phase II clinical trial.
Under the "play" of consumer medical care + serious medical care, JunHemeng's intention to quickly emerge in the industry is also obvious. However, for the time being, it is unclear whether this strategy can be consistently promoted and whether it can help companies achieve long-term development.
Botulinum toxin type A has been dynamic in the past two years. At the end of last year, YY001, a recombinant botulinum toxin type A product under development from Chongqing Yuyan, completed a phase I/II clinical trial in China for improving moderate to severe glabellar lines. During the same period, the company announced that it had met the pre-defined primary endpoint and would continue to advance the Phase III clinical trial of YY001.
The above study is the first recombinant protein botulinum toxin product under development approved for clinical trials in China, and the first recombinant botulinum toxin type A product under development in the world to enter the clinical stage. This also shows from the side that Junhemeng's recombinant botulinum toxin type A has no first-mover advantage in the development of glabellar lines. It may also be an important impetus for JunHemeng's recombinant botulinum toxin type A to start serious medical research.
Chongqing Yuyan is the holding company of Guangzhou Inming Biotech. With the clinical progress of YY001 taking the lead, the commercialization rights of this product in Chinese mainland, Hong Kong Special Administrative Region and Macau Special Administrative Region have been acquired by Huadong Pharmaceutical, an A-share listed company, and Huadong Pharmaceutical will be its exclusive distributor.
Compared with companies such as Chongqing Yuyan, Inming Biotechnology, and Huadong Medicine, which have already gained high-frequency attention in the field of medical aesthetics, JunHe Alliance has only gradually been more intensively exposed to the capital market after the second half of 2022.
Founded in November 2020, the full name is "Junhe Alliance Biopharmaceutical (Hangzhou) Co., Ltd.", and Leng Chunsheng, the former chairman of Tonghua Dongbao, an A-share listed company, is the actual controller. In May this year, Tonghua Dongbao increased its capital by 100 million yuan to invest in Junhe Alliance.
In addition to the differentiated competition in indication development, the technical route chosen by JunHemeng to recombinant botulinum toxin type A can also indicate that the industry is changing rapidly, and the long-term introduction of agency models may usher in changes. To put it simply, the technical route of reorganization can better avoid the risk of safe production, and it also gives the product advantages in terms of development time and production cost. As a result, some local companies with relevant technology accumulation may also be able to start this business.
According to Shen Yubao, R&D Director of CMC of JunHemeng, the host of JunHemeng's botulinum toxin type A product uses genetically engineered E. coli, which has a clear genetic background and safe cultivation operation, which is a safe host compared with the traditional botulinum toxin production strain, Clostridium botulinum. At the same time, botulinum toxin itself has extremely high toxicity and has a strong inhibitory effect on host cells during the expression process.
Shen Yubao further explained that compared with the traditional botulinum toxin preparation process, JunHemeng's purification steps are reduced by 50% and the process time is greatly shortened, while after adopting a simple and efficient preparation process, dozens of milligrams of high-purity recombinant botulinum toxin stock solution can be produced in batches by small-scale culture, and the 5L fermentation scale can fully meet the requirements of commercial scale. In addition, from the perspective of product quality, because JunHemeng's recombinant botulinum toxin type A products use recombinant technology instead of traditional extraction technology, the product has the characteristics of single active component, single subtype, high purity, high activity, and high batch-to-batch consistency, and is relatively safe for clinical application.
In addition, according to Xu Kui, chairman of JunHemeng, in order to rapidly promote the commercialization of recombinant botulinum toxin type A products, the company established Junhe Biopharmaceutical (Tonghua) Co., Ltd. in Tonghua, Jilin Province, as a production base for recombinant botulinum toxin type A products. At present, the production base has obtained a drug production license and is producing clinical trial samples of recombinant botulinum toxin type A.
Up to now, the approved botulinum toxin in China has been updated from 4 to 5. In addition to the domestically produced Hengli, Allergan's Botox, Ipsen's Fits, and Hugel's Letibao, Merz Aesthetics' Cyomy was also approved in March this year. Galderma and Sihuan Pharmaceutical, a Hong Kong-listed company, are the distributors of Jishi and Letibao in China, respectively.