The next card after GLP-1: Why are Eli Lilly (LLY.US) and Novo Nordisk A/S Sponsored ADR Class B (NVO.US) both betting on amylin?

Title context: The next card after GLP-1: Why are Eli Lilly (LLY.US) and Novo Nordisk A/S Sponsored ADR Class B (NVO.US) both betting on amylin? Text: Eli Lilly's Phase 2 clinical data released this week added a key piece to the obesity drug roadmap after GLP-1: its experimental amylin drug eloralintide, when used in combination with tirzepatide, achieved an average weight loss of 23.3% at 48 weeks in the highest-dose group, far exceeding the 14.8% seen with high-dose tirzepatide monotherapy. The goal of next-generation obesity drugs is not to replace GLP-1, but to stack on new weight-loss mechanisms. Eli Lilly (LLY.US) and Novo Nordisk A/S Sponsored ADR Class B (NVO.US) are developing a series of injectables, oral drugs, and combination regimens around amylina hormone released in the pancreas alongside insulin that helps regulate hunger and satietyto set a higher ceiling for weight-loss efficacy while offering alternatives for patients who respond poorly to GLP-1. Eli Lilly Phase 2 data: 23.3% weight loss, but tolerability remains unresolved Eli Lilly is advancing eloralintide on two tracksboth as a standalone therapy and in combination with its blockbuster drug tirzepatide. The Phase 2 trial announced this week targeted patients with obesity and type 2 diabetes, with the highest-dose combination group achieving an average weight loss of 23.3% at 48 weeks, compared with 14.8% for the high-dose tirzepatide monotherapy group. These data are based on an efficacy analysis, which assumes all enrolled patients completed the full course of treatment. Benjamin Bikman, a metabolic health expert at Brigham Young University, commented, "These results are encouraging. Patients with type 2 diabetes typically lose less weight on these types of therapies than non-diabetic patients." Leerink Partners analyst David Risinger predicts that Eli Lilly's eloralintide product line will reach annual sales of $23.2 billion by the end of 2035, with the monotherapy expected to launch in 2029 and the combination therapy following in 2030. He believes the standalone eloralintide could have even greater potential, because "there may be more than 10 million people who have tried GLP-1 but failed to achieve success due to insufficient efficacy, tolerability issues, or genetic factors." Ken Custer, President of Cardiometabolic Health at Eli Lilly, said in an interview: "Patients may not be able to get all the efficacy they need from tirzepatide, and they may not be able to get it from eloralintide monotherapy either." Bikman also believes that combination therapy offers new possibilities for patients whose weight loss on tirzepatide monotherapy has plateaued. But Eli Lilly still has much to prove. The data come from a relatively small Phase 2 trial, and Phase 3 trials will begin later this year. Tolerability is a key challenge: the proportion of patients who discontinued due to side effects ranged from 10.8% to 27% across the different-dose combination groups, compared with only 2.9% in the tirzepatide monotherapy group. Dr. Caroline Apovian, co-director of the Weight Management Center at Brigham and Women's Hospital, said bluntly, "27% is not a good number." Bikman also emphasized, "A therapy is only effective if patients can stay on it, so tolerability in Phase 3 trials will be as important as efficacy." Novo Nordisk A/S Sponsored ADR Class B's amylin strategy: CagriSema to launch next year Novo Nordisk A/S Sponsored ADR Class B has been building its presence in the amylin space for years. Its amylin drug cagrilintide has already shown significant weight-loss effects as a standalone therapy in a late-stage clinical trial. CagriSema, which combines cagrilintide with semaglutide, has demonstrated even greater weight loss in clinical studies and is expected to launch early next year, with standalone cagrilintide and high-dose CagriSema expected in 2028. New data released by Novo Nordisk A/S Sponsored ADR Class B this week show that CagriSema's effects extend beyond weight loss. In a one-year brain imaging (fMRI) study, the drug reduced "food noise"persistent thoughts about foodand improved organ and bone health. The study showed that CagriSema changed the brain's response to high-calorie foods in regions associated with craving, pleasure, and self-control in people with obesity or overweight. "The signals in the brain changed in a way that was associated with improved quality of life," Martin Holst Lange, Chief Scientific Officer of Novo Nordisk A/S Sponsored ADR Class B, said in an interview. Novo Nordisk A/S Sponsored ADR Class B is also developing amycretin (also known as zenagamtide), a drug that uses a single molecule to simultaneously mimic the effects of both GLP-1 and amylin hormones, being tested in both once-weekly injection and daily oral tablet forms, with positive Phase 2 clinical results announced earlier this year. The multi-target era: from dual-target to triple-target Amylin is not new. The United States approved the first amylin therapy more than two decades ago, but that drug required multiple daily injections, limiting its adoption. The new generation of amylin drugs currently in development are all long-acting formulations that can be injected once weekly. Amylin helps produce satiety, suppress appetite, and slow gastric emptyingeffects similar to GLP-1, but the two work through completely different mechanisms in the body. "Same result, different path," Bikman told CNBC. The logic of stacking the two mechanisms is intuitive: engaging multiple hormone signals simultaneously may produce greater weight loss while avoiding pushing a single drug's dose to its limit. This approach has extended beyond amylin. Tirzepatide itself is already a drug targeting both GLP-1 and GIP hormones, and Eli Lilly's experimental drug retatrutide goes further, targeting GLP-1, GIP, and glucagon simultaneously, reporting the largest weight-loss data to date in clinical trials. According to published data, the drug performs notably well in reducing liver fat, triglycerides, and fasting insulin. Pfizer Inc., Astrazeneca PLC Sponsored ADR, and Viking Therapeutics are also developing their own amylin products. It is still too early to judge whether amylin combination drugs are superior to tirzepatide or other next-generation therapies, with more clinical trials and regulatory approvals still ahead. But from dual-target to triple-target, from injection to oral, the competitive landscape of obesity drugs is rapidly diversifying. This article is reprinted from "Wall Street Insights," author: Gao Zhimou; GMTEight editor: Yan Wencai.