Why does a company's independent innovation bloom in all four seasons?

At the 2015 National Science and Technology Awards Conference held on January 8, the "Research and Industrialization of the Original Innovative Drug Esomeprazole" project by Livzon Pharmaceutical Group won the second prize for national scientific and technological progress in 2015. Livzon's chief scientist, Hou Xuemei, accepted the award at the Great Hall of the People. Why did this project, which started 14 years ago, win a national government award again after receiving the first prize for scientific and technological progress in Guangdong Province in 2013? What hardships did it go through? A reporter recently interviewed the project leader, Livzon's chief scientist, Hou Xuemei.

Innovation: Breaking the Monopoly of International Giants

"The technological level of the Esomeprazole project is leading domestically and has an advantageous position internationally, with significant social effects and good economic benefits," said Hou Xuemei. The successful industrialization of the Esomeprazole project has broken the long-standing technology and market monopoly of international pharmaceutical giants, significantly reducing the cost of medication for digestive diseases and promoting the development of public health in China, creating huge social and economic benefits.

According to reports, Esomeprazole is a new type of proton pump inhibitor (PPIs) that promotes the healing of gastrointestinal ulcers by inhibiting gastric acid secretion in the human body and increasing the pH value (acidity) in the stomach. It is the first and currently the only Class 1 patent new drug in the field of digestion in China, and also the only chemical Class 1 patent new drug in Guangdong Province in nearly 30 years.

Livzon is a well-known pharmaceutical company that started with gastrointestinal drugs. In 1989, an advertisement and slogan "In fact, men need care more" created a whirlwind for Livzon, bringing it from Zhuhai into thousands of households across the country. Twenty years later, Livzon hopes to create brilliance again in the field of gastrointestinal drugs after Livzon Dela.

Digestive tract diseases are common and prevalent, with an incidence rate of up to 10% in China, affecting about 130 million people. In 2014, the medical expenses for such diseases in China reached 21.5 billion yuan, placing a huge burden on families and society. Clinical treatment drugs mainly consist of proton pump inhibitors that suppress gastric acid secretion, which hold a market share of 94%. There are five similar drugs on the global market, all developed and monopolized by international pharmaceutical giants, and there are clinical deficiencies such as short acid suppression time, large individual differences, and many drug interactions; domestic pharmaceutical companies are all at a low level of imitation.

Therefore, Livzon's independently developed latest generation of proton pump inhibitors, Esomeprazole, was launched globally in 2008. Hou Xuemei said that Esomeprazole has the strongest acid suppression activity, with 5 mg equivalent to 20 mg of the similar drug Omeprazole; it also has a long duration of action, with one dose lasting a day; and it has fewer drug interactions.Esomeprazole enteric-coated tablets have been used by over 2.7 million patients in more than 1,700 hospitals nationwide, including Sun Yat-sen University First Affiliated Hospital, Zhongda Fifth Hospital, Shanghai Ruijin Hospital, and Changhai Hospital. Due to its significant efficacy, it has received high praise from doctors and patients.

The innovative research on Esomeprazole has been ongoing, with 37 invention patents applied for, of which 14 have been authorized domestically and 9 have been authorized in the United States, Europe, Japan, and other 9 countries. Due to the outstanding patent research work, it has received high praise from the European Patent Office. In 2014, at the meeting of deputy directors of intellectual property in China, the U.S., Japan, and South Korea, Esomeprazole was shared as a case study. The patent for Esomeprazole enteric-coated tablets won the Guangdong Provincial Patent Gold Award in 2014 and the National Patent Excellence Award in 2015. Hou Xuemei stated that since its launch in 2008, the cumulative sales of Esomeprazole have reached about 800 million yuan, and it is expected to grow rapidly at a rate of 65% annually, aiming to achieve annual sales of 2 billion yuan within the next five years.
 Belief: "We do not want to fall into the vortex of generic drugs!"

When the Esomeprazole project was initiated, it aimed at digestive ulcers in the gastrointestinal field. The clinical treatment drugs for digestive ulcers mainly consist of proton pump inhibitors (PPIs) that suppress gastric acid secretion, which is the type of new proton pump inhibitor that Livzon aims to develop.
Many people raised such doubts:

"There are nearly 6,000 pharmaceutical companies of all sizes across the country, with over 95% of them making generic drugs. Why and how can Livzon develop a Class 1 original innovative drug?"

Hou Xuemei said: "We want to take a different path, and we do not want to fall into the vortex of generic drugs!"

Regarding this strategy, Livzon Group Chairman Zhu Baoguo stated: After Livzon Dela, whether Livzon can provide new products in the field of gastrointestinal treatment is not only an unavoidable topic for the group but also an eager expectation from doctors and patients. The global development of new gastrointestinal drugs is also very eager for a brand new proton pump inhibitor as a replacement.

Evaluation: One, efficacy first; Two, made by Livzon; Three, safe and reliable.

In 1987, at the age of 19, Hou Xuemei graduated from Shenyang Pharmaceutical University and joined Livzon Group. In 2001, the Esomeprazole project was initiated, and Hou Xuemei became one of the leaders. In the initial years of the project, Hou Xuemei and her project team worked day and night, with each member cherishing this rare opportunity to test their research and development wisdom and capabilities.

However, the development of Class 1 new drugs posed severe challenges to the project team. From raw material processes, formulation processes, quality research, stability, and other pharmaceutical aspects, to animal safety and the effectiveness of clinical trials, every aspect, down to each specific operational parameter, had to be strictly controlled; otherwise, all previous efforts would be in vain.

Taking raw materials as an example, Hou Xuemei explained that the structure of Esomeprazole is more complex than that of other similar drugs. The initial raw materials and other reagents were not as easily obtainable as those for other similar drugs, requiring self-synthesis from scratch, involving 11 steps, "each step was more difficult than the last."
What worried the team even more was Esomeprazole's "delicacy." It is quite sensitive to external elements such as heat, light, and acid, and if not careful, it can degrade quickly, leading to impurities and discoloration. After repeated tests, some team members even suggested considering giving up.

With unwavering spirit and firm belief, Esomeprazole completed phase III clinical trials in 2006 and successfully obtained production approval in 2008. Subsequently, it received a more user-friendly name—Yilian. This name carries profound meaning: One, efficacy first; Two, made by Livzon; Three, safe and reliable.

"Esomeprazole 10mg can rival the currently clinically most effective imported product, 40mg Esomeprazole"; "Halving the dose means that 5mg Esomeprazole also has good efficacy for treating ulcers"... Esomeprazole has the strongest acid suppression activity, acts quickly, lasts long, and has no individual differences, receiving unanimous praise from medical staff and patients.

The National Development and Reform Commission praised the "High-tech Industrialization Demonstration Project of Innovative Drug Esomeprazole Raw Materials and Formulations" during its acceptance inspection, stating that it serves as a model for domestic companies to embark on the path of innovation. Professor Lin Sanren, former chairman of the Digestive Committee of the Chinese Medical Association, praised: "Esomeprazole is a typical case of the Chinese pharmaceutical industry exploring the path of independent innovation."
 

Achievement: 14 years of persistence and never giving up 

"I started working on the Esomeprazole project when my daughter was in elementary school, often bringing her to work overtime and having colleagues help with dictation. Later, she felt it was abnormal if I didn't work overtime, and now she is about to graduate from university. The energy spent on the project far exceeds that spent on my daughter, to the point where my daughter has developed excellent cooking skills and even educates me by saying: you should learn to cook too!" Speaking of this, Hou Xuemei is filled with guilt and comfort. The iron-clad camp has flowing soldiers, but Hou Xuemei has always been a pillar in the project team. Over the past 14 years, a total of 150 people have participated in the project, with R&D investment exceeding 200 million yuan. It is through the unremitting efforts of an excellent team that they have come this far.

Compared to many PhD and postdoctoral researchers engaged in scientific research, Hou Xuemei does not have an educational advantage. She graduated with a bachelor's degree in 1987 and was assigned to Lizhu, joining the project team at the project's inception. When she became the project manager in 2004, she was both excited and apprehensive, as developing innovative drugs and bringing them to market is a lifelong dream for many new drug researchers and even academicians. However, many around her doubted whether it could be done, with some even believing she might not succeed even if her hair turned gray. At one point, only a few people in the company believed in this project. During that time, she often woke up in the middle of the night to write the next day's plan, and after finishing, she couldn't sleep. Developing innovative drugs is inherently difficult, and Esomeprazole is particularly delicate, with major problems at every step and minor problems every day. "When everyone doubts, you must stick to your goals, and the methods must be scientific."

Market participants pointed out: Lizhu Group took 13 years to successfully develop the first Class 1 new drug in the digestive field, Esomeprazole, along with its new dosage forms and new indications. Although the R&D process for innovative chemical drugs is tortuous and lengthy, its revitalized lifecycle is unmatched by generic drugs. The Esomeprazole project won the National Science and Technology Progress Award (Second Class), which is not only an honor but also a recognition of the scientific research strength and economic benefits of Esomeprazole. This will help maintain the rapid growth of sales and expand the market further.

Today, Lizhu, standing at thirty, is speeding up its strategic transformation in biomedicine. The crowning of the National Science and Technology Progress Award is undoubtedly the loudest call.

There will be times when the wind and waves will break, and the sails will hang high to cross the vast sea!