On September 21, 2022, Zhengda Tianqing Pharmaceutical, a subsidiary of China Biopharmaceutical (01177.HK), signed an agreement with French biopharmaceutical company Inventiva for US$307 million, agreeing to develop and commercially promote Inventiva's patented compound lanifibranor to treat non-alcoholic steatohepatitis (NASH) and other potential metabolic diseases in China. Zhengda Tianqing Pharmaceutical will pay a $12 million advance payment, and if certain clinical milestones are met, Inventiva is expected to receive another $5 million in the short term. In addition, Inventiva is expected to receive clinical, regulatory and commercial milestone payments totaling up to $290 million under the terms of the agreement, as well as a tiered commission based on net sales.
01 Non-alcoholic steatohepatitis (NASH) - The new liver killer
Non-alcoholic steatohepatitis is a progressive chronic liver disease, also known as metabolic steatohepatitis. Its pathological changes are similar to alcoholic hepatitis , but the patient has no history of excessive drinking, which is more common in overweight and obese individuals, and in severe cases it will be life-threatening. The early stage of non-alcoholic fatty liver disease (NAFLD), which refers to the condition where fat accumulates in the liver. As fat continues to accumulate in liver cells and changes in the metabolic environment, liver cells become inflamed (swelling of the liver) and form liver tissue scars (fibrosis). In severe cases, it will lead to cirrhosis, , liver failure or hepatocellular carcinoma. The diagnosis of
NASH is extremely difficult, not only because patients usually present asymptomatic or only atypical NASH symptoms, but also because invasive liver puncture surgery with risk and technical limitations is required to be used to diagnose. Therefore, patients with NASH often seek reversal methods until the disease progresses to the late stage, but it is usually too late and can only choose to undergo liver transplantation, which is also the reason for the increasing number of liver transplants caused by NASH. However, liver transplantation is prone to multiple complications and may take a long time to wait for the donor of the liver.
Figure 1 Transformation of NASH lesions at each stage (Photo source: Inventiva official website)
Although viral hepatitis and alcoholic hepatitis are still the key issues of global liver diseases, the prevalence of non-alcoholic fatty liver has jumped to the top of liver disease in Western countries in the past few decades, while the prevalence of other chronic liver diseases has steadily decreased. According to statistics, there are currently 444 million NASH patients around the world, and there were about 32.8 million NASH patients in China in 2016, and it is estimated that it will reach 48 million by 2030. At present, both China and foreign countries have no formally approved treatment plans. Currently, a total of 5 NASH treatment drugs around the world have entered phase III clinical practice, of which only Lanifibranor and semaglutide, a subsidiary of Novo Nordisk, are likely to plan to conduct phase III clinical practice in China in the near future. The cooperation between China Biopharma and Inventiva will be expected to bring the first approved NASH oral drug to the domestic market.
02 Leading liver health layout NASH new layout
China Biopharma is a medical branch of Zhengda Group . Its subsidiary Zhengda Tianqing As a leading enterprise in China's "liver health" drugs, it has been focusing on the research and development of liver disease drugs since the 1980s, and is committed to providing patients with two major categories of drugs that protect liver disease, namely liver disease, enzyme protection, and antiviral infections. More than 30 years of persistence have made the market share in the liver disease field reach 25% of the country. In 1988, Zhengda Tianqing cooperated with a scientific research organization to launch the company's first liver disease treatment drug - Qianglining . In 2005, Tianqing Ganmei, the isoglycidyl injection, known as the " artemisinin in the field of liver disease", was launched, becoming the world's first pure trans isomer glycyrrhizate salt with more than 99% pure trans isomer glycyrrhizate, and the compound patent won the Chinese patent gold medal. In 2010, the generic drug Entecavir Runzhong was launched, allowing more than 3 million chronic hepatitis B patients to enjoy the same efficacy as the original drug with a high cost-effectiveness. In 2017, the new generation of antiviral drug Qingzhong (tenofovir ester) was launched. It is the only generic drug in China to conduct a 5-year "head-to-head" controlled trial with its original products. It is also the first anti-hepatitis B virus drug in China that was approved for marketing in EU .In addition to the field of liver disease, Zhengda Tianqing has also formed a strong product cluster in the fields of tumors, respiratory, infection, endocrine, cardiovascular and cerebrovascular diseases.
This cooperation with Inventiva is another proof that China Biopharma seeks innovative breakthroughs in its core therapeutic field - the field of liver disease. Xie Qirun, Chairman of China Biopharma, said: "For more than ten years, we have been at the forefront of helping China eliminate viral hepatitis . Now, NASH has become the fastest growth in liver transplantation and liver cancer , but NASH has not yet been approved for treatment. We are very happy to sign this agreement with Inventiva, which is a great opportunity to bring NASH treatment methods to China."
Figure 2 Chairman and Executive Director of China Biopharma Board of Directors: Ms. Xie Qirun (Photo source: China Biopharma Official Website)
Get the Lanifibranor of China Biopharma this time, which is the most promising oral small molecule that is expected to win the lead among the candidates for Inventiva for the treatment of NASH. Lanifibranor is a class of peroxisome proliferator-activated receptor (PPAR) agonists that induce antifibrosis, anti-inflammatory and beneficial vascular and metabolic changes in vivo by activating all three subtypes of PPAR, thus potentially addressing all key features of NASH: inflammation, steatosis, swelling and, most importantly, fibrosis . In recent phase IIb trials, lanifibranor has demonstrated effects on both NASH regression and fibrosis. While there are other PPAR agonists that are activated only on one or two PPAR isoforms, lanifibranor is the most advanced pan-PPAR agonist used in clinical development for the treatment of NASH. Inventiva believes that the moderate and balanced pan-PPAR binding spectrum of lanifibranor contributes to the good tolerance spectrum observed so far in clinical trials and preclinical studies. Currently, lanifibranor has been certified and fast-track qualification for breakthrough therapies for FDA for the treatment of NASH.
According to the agreement, all costs of Lanifibranor's trials in China will be borne by Zhengda Tianqing, and a variety of factors will determine whether Zhengda Tianqing will join the ongoing NATiV3 Phase III clinical trial of Lanifibranor or conduct independent research. Sean Chen, chief strategy officer of China Biopharma, expressed his strong optimism for this cooperation. Lanifibranor has the potential of best-in-class and is believed to help China Biopharma further enrich its innovative channels in liver disease and consolidate its leadership in this therapeutic field.
However, China Biopharma's layout of NASH is not only in PPAR targets. Through self-development and authorization introduction, it has now comprehensively covered small-molecular drug targets such as FXR and THR-β and large-molecular drug targets such as GLP-1 and FGF-21 that have been verified of concepts. It can be seen that in order to further expand its market share and continue to maintain a leading position in the field of liver disease, China Biopharma has far-reaching plans.
Written by | Feng Lixiao
Typesetting | Feng Lixiao
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Reference materials:
[1]https://www.globenewswire.com/news-release/2022/09/21/2520615/0/en/Inventiva-and-Sino-Biopharm-announce-licensing-and-collaboration-agreement-to-develop-and- commercialize-lanifibranor-in-Greater-China.html
[2]https://www.cn-healthcare.com/article/20200317/content-532777.html
[3]https://inventivapharma.com/therapeutic-areas/non-alcoholic-steatohepatitis-nash/
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