Tirzepatide

2023年5月25日，Carmot Therapeutics宣布完成1.5亿美元E轮融资，用于推进GLP-1/GIP双靶点激动剂新药等的临床开发。 Carmot Therapeutics成立于2008年，创始人为Stig K. Hansen，研发管线包括GLP-1/GIP双靶点多肽，GLP-1小分子受体激动剂等。该公司已经完成多轮融资，2018年1月完成1500玩美元B轮融资，2020年9月完成4700万美元C轮融资，2022年7月完成1.6亿美元D轮融资。 Stig K. Hansen曾任职于Sunesis Pharmaceutical，担任生物学总监，在这里他发明了Chemotype Evolution（CE）技术。安进在开发KRAS G12C抑制剂的时候，即与Carmot合作，结合CE技术开发出了Sotorasib。 总结 GLP-1在商业上已经获得巨大成功，临床需求强劲，包括糖尿病和二型糖尿病，同时在探索多项新适应症。礼来Tirzepatide为全球首款GLP-1/GIP双靶点激动剂，上市后放量速度远超之前度拉糖肽和司美格鲁肽，今年一季度销售额5.7亿美元，预计全年可能突破30亿美元。 内容来源于网络，如有侵权，请联系删除。

Pictured: a scale and tape measure_iStock, Tatiana Sviridova To assert their position in the multibillion-dollar obesity market, pharmaceutical titans Eli Lilly and Novo Nordisk have intensified their competition. Eli Lilly recently registered a Phase IIIb clinical trial, SURMOUNT-5, according to ClinicalTrials.gov. The trial compares Lilly’s Mounjaro with Novo’s Wegovy in obese or overweight patients with weight-related health conditions. Obesity impacts 650 million people worldwide and nearly half of Americans. It is a chronic disease with limited treatment options that increases the risk of other weight-related conditions, such as diabetes and heart disease and affects overall health, according to the American Diabetes Association. The side-by-side study will enroll 700 participants from 61 sites across the U.S., Canada, South America and several European countries. It began in April; Lilly expects its completion around January 2025. The study’s primary endpoint will compare the weight loss percentage from baseline between the two drugs after the trial period. Likely, say observers, Lilly intends for SURMOUNT-5 to establish that Mounjaro performs better than Wegovy, with fewer side effects. Secondary measurements will assess the percentage of patients who achieve a certain magnitude of weight loss. The Mechanism Wegovy (semaglutide) stimulates the hormone glucagon-like peptide 1 (GLP-1) alone, while Mounjaro (tirzepatide) stimulates GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). By targeting two receptors, Lilly’s drug stands to have a more significant effect, said Michael Glickman, an obesity medicine specialist at Revolution Medicine, Health & Fitness. “Looking at all the data, I think the assumption is that if we target more receptors that have a lot of these overlapping mechanisms, we’ll see better results,” Glickman told BioSpace. Glickman added that when patients’ insurance allows for coverage of Mounjaro, or they can afford it out of pocket, it may be the best choice. Though the SURMOUNT-5 trial will bear data, at least anecdotally, some patients prefer Mounjaro, he said. Lilly representative Jessica Thompson said she expected the data to bear this out in the two-target approach. “GIP and GLP-1 are hormones the gut produces in response to the nutrients in food,” Thompson told BioSpace via email. “GIP and GLP-1 have diverse roles in the body and are responsible for the incretin effect. In healthy humans, GIP is responsible for nearly two-thirds of the incretin effect, generating a more significant impact on insulin secretion than GLP-1. GIP is also responsible for regulating body weight through appetite and food intake.” Glickman said what’s most salient is assessing how these medications affect the body’s metabolic set point. Unlike metabolism, which can go up or down depending on diet, exercise and hormonal factors, the metabolic set rate remains fixed. Generally, this is why short-term diets fail—they don’t alter the set point. However, GLP-1 agonists can. “The new, evidence-based way of thinking about obesity is not the appetite,” Glickman said of appetite suppressants.” It’s the set point. If we lower the set point, natural hunger will come down as a secondary byproduct of that treatment … that’s the subjective experience of these medicines.” There are many complex mechanisms in the body, he said, adding, “we also see improvements in insulin resistance and optimizations of how the body processes glucose.” This has been the case with Wegovy and Ozempic (semaglutide marketed for Type 2 diabetes) alike. Both drugs have garnered significant public attention thanks to mention from Hollywood stars, an unexpected promotion by Twitter owner Elon Musk and viral posts on TikTok and other social media platforms. Despite their recent inclusion into the American zeitgeist, GLP-1 weight loss drugs have been approved for some time. Wegovy received approval in 2021; Ozempic in 2017. Even Mounjaro has been approved for a full year now. Glickman said patients often see family, friends or co-workers losing weight and come to learn they may be on a GLP-1 drug, leading them to seek treatment for themselves. More recently, regular media coverage has increased interest. “Weight loss can be very contagious,” he said. It’s a very different conversation today than what we were having with people compared to a few years ago.” Obesity Market Could Reach $50B by 2030 The tremendous unmet need for weight loss has resulted in staggering sales projections. In fall 2022, analysts at UBS projected that Mounjaro could reach peak sales of $25 billion, primarily in treating diabetes and obesity, according to Market Watch. However, more cautious analysts have estimated the potential to be at or below $10 billion. A report by TD Cowen analysts in December suggested that the global obesity drug market could reach $30 billion by 2030, with Novo and Lilly leading the charge. Earlier research by Morgan Stanley placed the number even higher at $50 billion. While Wegovy is administered at 2.4mg once weekly (it received FDA approval for chronic weight management in obese and certain overweight patients in 2021), Lilly’s Mounjaro is currently approved only for treatment of Type 2 diabetes (T2D). Lilly has recently initiated a rolling submission to the FDA for Mounjaro in obesity, with plans for a launch later this year. Lilly may choose a different brand name for tirzepatide in obesity, similar to how Novo’s semaglutide injection is known as Ozempic for T2D. To be eligible for the new SURMOUNT-5 trial, patients must have a body mass index of at least 30kg/m2 or at least 27kg/m2 along with a prior diagnosis of at least one of four weight-related disorders: hypertension, dyslipidemia, obstructive sleep apnea and cardiovascular disease. These criteria align with the FDA-approved patient population for Wegovy. The launch of SURMOUNT-5 coincides with the anticipated release of SURMOUNT-2, the second of two Phase III trials conducted by Lilly to support FDA approval of Mounjaro for obesity treatment. Lilly’s Commercial Strategy Thompson said it’s too early to determine the company’s commercial strategy for GLP-1 drugs as a single-ingredient treatment. “We are evaluating the merits of a single or dual trade name, but this will ultimately be dependent upon acceptance by regulatory agencies,” she said, adding that it is premature to comment on Lilly’s commercial strategy with respect to potentially launching one or two brands for tirzepatide. From Glickman’s perspective, the forecast for the use of weight loss medications like Wegovy or Mounjaro will largely depend on insurance coverage or, at the moment, the lack thereof. Instead of thinking of obesity as a personal failure to follow a diet and exercise regimen, we need to remember it’s a disease, he said. “If you have a friend or family member come up to you and say, ‘I was just diagnosed with stage four breast cancer,’ that person will not say, ‘What did you eat for breakfast? How much exercise have you been getting?’ Obesity should be treated like every other disease, and it's not by any means,” Glickman said. Novo Nordisk did not respond to BioSpace’s inquiries for comment for this article. Lisa Munger is a senior editor at BioSpace. You can reach her at lisa.munger@biospace.com. Follow her on LinkedIn.