Many Seek Beauty: 380 Million Investment, Long-Lasting Botulinum Toxin Approved

China has approved a new long-lasting formulation

Botulinum toxin, commonly known as Botox, is a bacterial exotoxin produced by the bacterium Clostridium botulinum. It has a strong neuromuscular blocking effect, primarily acting by binding to specific receptors on the presynaptic membrane of nerve endings, affecting the fusion of synaptic vesicles with the presynaptic membrane, and blocking the release of neurotransmitters such as acetylcholine. This results in muscle relaxation and gland secretion disorders, leading to chemical denervation effects.

Since the FDA approved the world's first clinically used botulinum toxin, Onabotulinum toxin A, in 1989, botulinum toxin has become an important neuromodulator and is now widely used worldwide in various medical and cosmetic indications, as well as in the fields of neurology, rehabilitation, and urology.

In early September 2024, Sisram Medical Technology Co., Ltd. (referred to as "the Company" or "Sisram Medical Technology") announced that its long-lasting Type A botulinum toxin product, marketed under the trademark DAXXIFY® (development code RT002), has officially been approved for sale by the National Medical Products Administration (NMPA) of China. This product is intended for the temporary improvement of moderate to severe glabellar lines caused by the activity of the corrugator or procerus muscles in adults, making it the first DaxibotulinumtoxinA-lanm product to receive market approval in China.

RT002 utilizes patented Peptide Exchange Technology (PXT) in combination with botulinum toxin and does not contain human serum albumin or animal-derived components. The currently approved specification in China is 100 units per vial, with the approval number: Guoyaozhunzi SJ20240041.

BD&License Transactions:

Fosun Pharma acquired exclusive rights for the import, use, development, and commercialization (excluding manufacturing) of the product in China from the US-listed company Revance Therapeutics, Inc. in December 2018. In December 2022, Fosun Pharma sublicensed the related commercialization rights for cosmetic indications (such as the improvement of moderate to severe glabellar lines in adults) to its subsidiary, Sisram Tianjin. As of July 2024, the cumulative R&D investment is approximately 380 million yuan (including licensing fees).

In 2023, global sales of injectable Type A botulinum toxin products were approximately $2.453 billion; in 2023, sales of injectable Type A botulinum toxin products in China were about 687 million yuan.

Twists and Turns in Development, Recent Acquisition

On August 12, 2024, Crown Laboratories announced the acquisition of all outstanding shares of Revance Therapeutics for $6.66 per share in cash, totaling approximately $924 million. This represented an 89% premium over Revance's closing price on August 9. In 2023, Daxxify generated $84 million in revenue for Revance. In the second quarter of 2024, the drug's net revenue grew to $28.7 million, a 27% increase year-over-year.

Unexpected Discovery of a Potential Product

Revance Therapeutics was initially registered under the name Essentia Biosystems in Delaware, USA, in August 1999 and began operations in Silicon Valley in 2002. The company originally focused on exploring the potential applications of peptides for macromolecular delivery in disease diagnosis and treatment, including immunomodulators, insulin, and botulinum toxins, especially the development of new types of botulinum toxin. In April 2005, the company changed its name to Revance Therapeutics, a move spearheaded by Rowland Hanson, a board member at the time (who was an early employee of Bill Gates and named Microsoft Windows).

At that time, Revance's primary development product was a topical A-type botulinum toxin gel, RT001, which used the company's proprietary TransMTS® peptide delivery technology to carry botulinum toxin to the dermis with the patented peptide RTP004 for release. Revance also collaborated with medical device supplier Duoject Medical Systems to design a proprietary single-use delivery device for RT001. In 2007, Revance initiated clinical trials for RT001 for crow’s feet (lateral canthal lines) and began trials for axillary hyperhidrosis in 2008. The concept of a topical botulinum toxin was highly popular upon introduction, and in 2014, the company successfully went public on NASDAQ (NASDAQ: RVNC).

However, the subsequent clinical trial results for RT001 did not meet expectations. In 2016, Revance announced that the Phase 3 clinical trial for RT001 in treating moderate to severe crow’s feet did not achieve its co-primary endpoints or other endpoints, leading to the decision to discontinue development for this indication. The clinical development plan for axillary hyperhidrosis was also terminated. The company's development focus then shifted to a second candidate product—long-lasting injectable botulinum toxin RT002 (DaxibotulinumtoxinA), later branded as DAXXIFY™ (DaxibotulinumtoxinA-lanm).

The discovery of RT002 has a serendipitous quality. Dr. Ellen Marmur, a member of the scientific advisory board at Revance Therapeutics, revealed in an interview that while developing the topical botulinum toxin, the FDA required a comparison of this new molecule with the current gold standard, which is injectable Type A botulinum toxin. However, the team unexpectedly discovered that the injectable botulinum toxin they developed had a longer duration of effect than traditional botulinum toxins.

In 2012, Revance completed the first human trial of RT002 (DaxibotulinumtoxinA) in Mexico, and in 2014, it initiated clinical trials for DaxibotulinumtoxinA to treat glabellar lines, cervical dystonia, and plantar fasciitis. In 2017, Revance announced that DaxibotulinumtoxinA (RT002) achieved its primary and all secondary endpoints in the pivotal Phase 3 SAKURA trial, demonstrating sustained efficacy for up to six months.