Almost one in every two adults is overweight or obese, and this lawsuit must be fought, and the weight loss market is being fought over
Text | Caijing reporter Xin Na intern Wang Weining
Edit | Wang Xiao
In early February 2022, multinational pharmaceutical company Pfizer sued two former employees and its company, Qilu Ruige, for stealing trade secrets related to the diabetes and obesity treatments Pfizer was developing.
In its pleadings, Pfizer argued that the drugs introduced by the defendant company were "strikingly similar" to Pfizer and applied for a patent. The lawsuit is currently pending in federal court in Connecticut.
Pfizer's drug, the oral administration of small molecule GLP-1 receptor agonists, is the focus of the lawsuit. GLP-1, a hormone secreted by intestinal cells that regulates body weight using a variety of mechanisms, is considered a trump card in the future weight loss market.
At present, the oral small molecule GLP-1 receptor agonist developed by Pfizer, Eli Lilly and the defendant company Qilu Ruige in this lawsuit are going hand in hand to compete for the new generation of oral diet drug market. Eli Lilly also entered into a collaboration of more than $1.5 billion with Qilu Reger in December 2021 to jointly develop new therapies for metabolic diseases.
The Pfizer lawsuit requires that the defendant transfer the right to apply for a patent to Pfizer, stop using its trade secret, and compensate for the losses.
Behind this lawsuit is the weight reduction market that major pharmaceutical companies are competing for. For Pfizer, the success or failure of this lawsuit is very important. A pharmaceutical practitioner believes that if there is no patent, the other party is still cooperating with Eli Lilly in depth, and Pfizer may lose the opportunity in this field.
Lu Yiguang, vice president of the Life Law Research Association of the Shanghai Law Society and a lawyer at Shanghai United Law Firm, believes that due to the particularity of the common law system itself, the litigation may last for several years. The lawsuit may have a negative impact on the defendant's business reputation and future development.
Pfizer sued former employees for stealing trade secrets
According to the Pfizer indictment, Pfizer sued two former employees, Min Zhong and Xiayang Qiu, accusing it of stealing key data from the company and creating Regor Therapeutics, based in Cambridge, Massachusetts, and QILU Regor Therapeutics in Shanghai, China.
Founded in 2018, the Shanghai-based company is a company focused on three therapeutic areas: oncology, immunity and metabolism. Previously, it received a $90 million Series B round of funding led by Eli Lilly Asia Fund.
Zhong and Qiu have been working at Pfizer since the beginning of 2000. Qiu's work focuses on discovering new compounds, while Zhong is responsible for collaborating with external researchers to analyze samples of compounds in toxicology studies.
The Pfizer indictment mentions that the defendants conspired to steal Pfizer's trade secrets in 2018, when they were still at the company, meeting with potential collaborators in China, drafting contracts related to the formation of the new company, and founding the new company, Regor Therapeutics, before leaving Pfizer.
Two months before Mr. Chung and Qiu left, a confidential document without Pfizer's confidentiality mark was uploaded to their personal accounts. Later, in a new presentation, they used the information "about a revolutionary new diabetes and obesity drug," Pfizer mentioned in the indictment, detailing classified information about its glucagon-like peptide 1 (GLP-1) program.
Two former Pfizer employees filed patent protection for the diabetes and obesity treatment months after starting the new company. Pfizer mentioned in its pleadings that the defendant applied for patent protection and thus obtained a treatment that was "strikingly similar" to Pfizer. "In such a short period of time, it is impossible to develop this treatment without theft".
The Pfizer lawsuit requires the defendant to transfer the right to apply for a patent to Pfizer, stop using its trade secrets, and compensate for losses.
Lu Yiguang analyzed that the definition of trade secrets is different in different countries. In China, for example, trade secrets are mainly embodied in the Anti-Unfair Competition Law, which defines "information of great commercial value to the company and requires confidentiality measures" as trade secrets, such as financial and technical secrets. Companies generally restrict employees by formulating labor contracts or systems. Pfizer's choice to sue also has its own interests in mind.
The relevant person in charge of Pfizer China replied to "Finance and Economics Big Health" that the lawsuit was responsible for Pfizer's headquarters and did not understand the progress of the incident. The relevant person in charge of Qilu Ruige responded that he believes that the Pfizer lawsuit is groundless and will make every effort to defend and safeguard legitimate rights and interests.
The coveted oral weight loss innovation
Previously, the first product launched by Qilu Reger is RRT-075 (once a day oral), which can be used to treat type II diabetes, obesity, non-alcoholic fatty liver and other indications. It is an oral small molecule GLP-1R agonist that has completed Phase Ph1b clinical studies in the United States.
Existing studies have found that the body's appetite and energy utilization are controlled by the neuroendocrine system in the brain. GLP-1, as a hormone secreted by intestinal cells, can regulate body weight through a variety of mechanisms.
In addition to stimulating insulin secretion, inhibiting glucagon secretion and thus promoting blood glucose metabolism, it can also directly act on GLP-1 receptors in the gastrointestinal tract, inhibit gastrointestinal peristalsis, slow down the absorption of nutrients and reduce the amount of food intake. In addition, it can also act on the GLP-1 receptors in the brain center and play an appetite-suppressing role.
In December 2021, Qilu Reger announced a partnership with Eli Lilly, a multinational pharmaceutical company, to jointly develop innovative therapies for metabolic diseases in the coming years.
According to public reports, Qilu Reger will grant Eli Lilly an intellectual property license for new drugs, which Eli Lilly can choose to extend. Eli Lilly will be responsible for clinical development, production and commercialisation outside of Greater China, and QiluRiger will retain the above interests in Greater China, as well as advance payments totaling US$50 million, including some equity investments.
In addition, QiluRiger will receive up to $1.5 billion in potential preclinical, clinical development and commercialization milestone payments, as well as a share of global sales.
In its complaint, Pfizer said that in the transaction between Qilu Reger and Eli Lilly, it included the license of the small molecule GLP-1 receptor agonist patent. "When Qiu and Zhong left the company, they had been working on the small molecule GLP-1 receptor agonist technology in different ways."
In the Pfizer submission, there are documents describing the interaction of small Pfizer molecules with GLP-1 receptors. Pfizer says it spends millions of dollars on research and development, and "competitors with this information can quickly design and screen for active GLP-1 receptor agonist compounds."
Globally, the GLP-1 receptor is becoming a popular target for the development of weight loss drugs. Previously approved drugs were injectable. Oral medications can make medication easier for patients and may improve medication adherence, resulting in better weight loss results. Therefore, oral drugs replacing injectable drugs are becoming a hot topic of exploration.
Pharmaceutical companies are also competing for a huge oral GLP-1 receptor agonist market position, and each has its own strategy. Novo Nordisk adopts peptide preparation transformation, and pharmaceutical companies such as Pfizer and Eli Lilly use oral small molecule heterocyclic GLP-1 receptor agonist drug research and development.
The oral series of small molecules in the Pfizer lawsuit Qilu Regal has entered phase II clinical trials in the United States, ranking first in the world's research and development echelon with Pfizer and Eli Lilly. In the case of extremely fierce competition on the same route, two opponents in the first echelon "held hands" successfully, which made Pfizer have to be vigilant.
"Now these three oral drugs are the fastest in global clinical trials, and if Qilu Ruige and Eli Lilly cooperate successfully, it is bound to have a great impact on Pfizer's entry into the heavyweight drug market." A drug developer analyzed the "Finance and Economics Big Health".
Who can win diet pills?
Obesity is a problem that plagues the world.
An article published in May 2021 in The Lancet Diabetes and Endocrinology revealed data from China: The prevalence of overweight and obesity among adults aged 18 and over in China exceeded 50% for the first time. It also means that almost one in two adults is overweight or obese.
People are racking their brains to lose weight, and the U.S. Food and Drug Administration (FDA) has approved at least seven long-term obesity treatment drugs.
However, apart from bariatric surgery, there are few treatments that are particularly effective. According to the analysis of the above-mentioned drug developers, "either the side effects are too large, or the weight loss effect is not enough." "Diet pills rimonaban and sibutramine increase the risk of mental and vascular diseases and are withdrawn from the market worldwide. As an oral anorexia, bupropion has been approved by the FDA for short-term treatment of obesity, but has not been recommended by guidelines.
The first FDA-approved GLP-1 receptor agonist therapy to treat obesity was liraglutide, discovered by Novo Nordisk scientists during the development of this hypoglycemic drug. The drug significantly reduced the weight of diabetics, after which they began clinical trials in patients with common obesity, and the drug was approved in the United States in 2014 for weight management in obese and overweight people. This opens the door to the development of another weight-loss drug.
According to data from a 2015 study published in the New England Journal of Medicine, in a clinical trial of 3731 overweight or obese subjects, about 33.3 percent of subjects in the liraglutide-using group (11 percent in the control group) lost more than 10 percent of their body weight.
Today, liraglutide has become a star drug in the weight loss market, bringing high returns to Novo Nordisk. Its financial report shows that the drug's sales in 2020 have reached $859 million.
In addition, Novo Nordisk's other GLP-1 receptor agonist, smegluotide, was also approved in the United States in June 2021 for long-term weight control in patients with overweight or obesity.
According to Data from Phase 3 Clinical Trials published in the New England Journal of Medicine, in a clinical trial of nearly 2,000 participants, smeglutide reduced the average patient's weight by about 15%, significantly exceeding the control group's 2.4%.
The above-mentioned drug developers believe that in addition to the side effects of traditional drugs, most of the weight loss effects are 5% to 10%, and if you can lose weight by more than 15%, it is very attractive.
A review in the journal Nature reviewed that the successful development of GLP-1 receptor agonists marks the arrival of a new generation of weight loss therapies. The development of advanced therapies has led to a belief that breakthrough, drug-based obesity management is possible.
This also makes GLP-1 receptor agonists a hot target for weight loss drugs in recent years, and it is Pfizer that mainly involves drugs in this lawsuit.
If you look at the development of single-target drugs, taking GLP-1 receptor agonists as an example, some "volumes" have begun to be. However, "there is still a lot of room for joint agonist development, or dosage form optimization." The above-mentioned pharmaceutical company R & D sources said,
In June 2021, a report by Frost & Sullivan showed that at that time, of the 12 drugs that entered the clinical trial pipeline of China's obesity treatment drugs, seven of them chose the same single target, of which five had entered the third phase of the clinic, from Renhui Biologics, Eli Lilly, Jiuyuan Gene, Wanbang Biochemical and Novo Nordisk.
Two other dual agonists, both selected GLP-1 and glucagon receptors, from Boehringer Ingelheim and Innovent Biologics, respectively, entered phase II of the clinic.
Developers are still trying to develop weight loss therapies that can selectively target GLP-1, GIP, and glucagon signaling pathways simultaneously. At the forefront is Eli Lilly's Tirzepatide, the world's first glucose-dependent insulin-stimulating polypeptide (GIP) and GLP-1 bi-receptor agonist.
Integrating the effects of the two insulinotropics into a single molecule, Tirzepatide has reduced patient weight by more than 10 percent in a Phase 3 clinical trial treating obese patients with type 2 diabetes. Not only that, but it has also changed the traditional injection drug and optimized it into oral preparations.
The industry generally believes that this product will become the trump card product in the field of diabetes treatment and weight loss in the future. If Pfizer loses the advantage of oral efficacy of single-target GLP-1 receptor agonists this time, it will be difficult to open up the weight reduction market in the future.
