Core Viewpoint - The article discusses the urgent need for new mechanisms in obesity treatment, highlighting the development of a novel siRNA candidate drug, SGB-7342, by Shengyin Biotech, which targets INHBE for obesity treatment [4][11]. Group 1: Obesity as a Public Health Challenge - Obesity is a chronic metabolic disease characterized by abnormal or excessive fat accumulation, significantly increasing the risk of cardiovascular diseases, type 2 diabetes, and various cancers [5]. - The global population of obese individuals has surpassed 1 billion and is expected to reach approximately 1.37 billion by 2035; in China, there are about 180 million adult obesity patients [6]. Group 2: Current Treatment Limitations - Current mainstream obesity treatments primarily involve GLP-1 receptor agonists, which suppress appetite through the central nervous system but have drawbacks such as gastrointestinal side effects, muscle loss risk, and weight regain after discontinuation [7]. Group 3: RNAi Therapy as a New Approach - RNAi therapy offers a differentiated treatment strategy that does not rely on central appetite regulation, aiming to regulate fat metabolism at the source by targeting key genes involved in fat breakdown and storage [8]. - This approach is expected to selectively reduce fat while preserving muscle mass and improving overall metabolic health, potentially lowering the risk of adverse effects associated with traditional therapies [8]. Group 4: INHBE as a Novel Metabolic Target - The INHBE gene, primarily expressed in the liver, encodes the secreted protein Activin E, which regulates fat breakdown and energy storage by binding to the ALK7 receptor in adipose tissue [9]. - Genetic studies indicate that individuals with INHBE loss-of-function mutations exhibit favorable metabolic traits, providing a biological basis for targeting INHBE in drug development [9]. Group 5: SGB-7342 Candidate Drug - SGB-7342 is a siRNA candidate drug targeting INHBE for obesity treatment, utilizing Shengyin Biotech's proprietary GalNAc conjugation delivery technology for precise liver targeting [10]. - The mechanism involves silencing INHBE mRNA in the liver to lower Activin E protein levels, promoting fat breakdown without inducing muscle loss, thereby improving metabolic disorders and insulin resistance [10]. - Preclinical studies show that SGB-7342 leads to significant weight loss and improved body composition while maintaining muscle mass, demonstrating good safety and tolerability [10]. Group 6: Future Outlook - Obesity is recognized as a complex systemic metabolic disease rather than merely a weight issue, with significant unmet clinical needs in the global obesity treatment landscape [11]. - RNAi therapy, with its novel mechanism directly targeting metabolic pathways, is expected to offer differentiated advantages in selective fat reduction, muscle protection, and long-lasting treatment [11].

Core Insights - Alnylam Pharmaceuticals is a leader in RNA interference (RNAi) therapeutics, focusing on treatments for rare diseases and cardiovascular conditions [1][6] - The company's revenue growth is driven by a diverse product lineup, including key drugs like Amvuttra, Givlaari, and Oxlumo [1][6] - Alnylam is conducting the ZENITH global Phase 3 trial for zilebesiran to advance its cardiovascular research [1] Financial Performance - In the first half of 2025, Alnylam's rare disease drugs generated $236.8 million in revenues, marking a 16% increase from the previous year [4] - The company has a negative price-to-earnings (P/E) ratio of -185.46 and a high debt-to-equity ratio of 5.18, indicating financial challenges [4][6] - Despite these challenges, Alnylam's current ratio of 2.80 suggests a strong ability to cover short-term liabilities [5][6] Product Development - Amvuttra has received approval in the U.S. and EU for treating polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis and ATTR amyloidosis with cardiomyopathy (ATTR-CM) [3] - The success of Amvuttra is attributed to new patient initiations and transitions from Onpattro, Alnylam's first FDA-approved drug for hATTR amyloidosis [3]

Core Viewpoint - Sanofi has confirmed the cessation of the supply of Alirocumab injection (brand name: Praluent) in the Chinese market due to global raw material supply issues and a strategic shift in its cardiovascular market approach [1][3][5] Group 1: Product Information - Alirocumab is the first PCSK9 inhibitor approved globally, entering the Chinese market in December 2019, with indications for cardiovascular event prevention and lowering LDL cholesterol levels [2][3] - The drug was included in the national medical insurance directory in 2021, with its price reduced from 1982 yuan to 306 yuan per injection [2] Group 2: Market Dynamics - The competitive landscape for PCSK9 inhibitors is intensifying, with more domestic products being included in the 2025 National Medical Insurance Drug List, leading to a more diversified market [5][6] - The PCSK9 drug market in China is projected to reach 8.9 billion yuan by 2030, with a compound annual growth rate of 43.5% from 2022 to 2030 [6] Group 3: Company Strategy - Sanofi is optimizing its cardiovascular product pipeline and has acquired rights to develop and commercialize new drugs in the region, including aficamten and the investigational drug Plerixafor [3][7] - The company aims to align its product and pipeline decisions with China's health policy directives, focusing on chronic disease prevention and treatment [8]