Retatrutide

Bengaluru: Eli Lilly said on Thursday its next-generation obesity drug helped patients lose an average of 28.7% of their weight in a late-stage trial, outperforming its blockbuster drug Zepbound and reinforcing the company's lead in the fast-growing market. The global obesity market has surged in recent years on strong demand for GLP-1-based drugs like Zepbound and Novo Nordisk's Wegovy, prompting drugmakers to invest heavily in next-generation treatments that could deliver faster, deeper, or more durable weight loss. BMO Capital Markets analyst Evan Seigerman called it the "highest weight loss to date", adding it may surprise investors with the magnitude of weight reduction demonstrated. The once-weekly injected drug, retatrutide, is designed to mimic the action of the GLP-1 hormone, which helps regulate blood sugar, slow stomach emptying and decrease appetite. Lilly, in its first late-stage trial readout, said the highest dose of the drug delivered weight loss of up to an average of 71.2 pounds at 68 weeks, along with substantial relief from deep-aching joint pain when tested in participants with obesity and osteoarthritis of the knee. TRIAL DEPARTURES ATTRIBUTED TO EXCESSIVE WEIGHT LOSS Lilly said that perceived excessive weight loss, particularly among those with lower body mass indexes (BMI) at the start, was behind some choosing to leave the trial. About 18.2% of patients who received the highest dose discontinued the trial, compared to 4% on placebo. Among people whose BMI was greater than 35, the discontinuation rate was 12.1% for the highest dose versus 4.8% for placebo. J.P. Morgan analyst Chris Schott said retatrutide tolerability was somewhat worse in the trial than what was reported for Zepbound but said it was "not surprising". Overall, side effects were in line with those typically seen in weight-loss treatment trials, the company said, including gastrointestinal issues such as nausea, diarrhea, constipation and vomiting. Dysesthesia, an abnormal skin sensation, occurred in 20.9% of patients on the highest dose. Seigerman said dysesthesia rates were "elevated" and that he would look to full data to be presented to better assess the severity of these events. Shares of Lilly, which last month became the first drugmaker to hit the $1 trillion valuation, rose 2.5% in morning trade. "Lilly is not up that much today, which I think confirms that the overall profile of retatrutide in this study seems indeed somewhat mixed, versus its expectations", said Kepler Cheuvreux analyst David Evans. IMPACT ON KNEE PAIN Lilly said a post-hoc analysis of the data showed that participants' pain scores were reduced by up to an average of 4.5 points, with more than 1 out of 8 patients free from knee pain at the end of the trial. The company said on Thursday seven late-stage trials evaluating the drug in obesity and type 2 diabetes are expected to be completed in 2026. "For Lilly, this is likely another blockbuster drug with a long patent duration and adds to a full suite of solutions that physicians can tailor to individual patient needs," said Kevin Gade, chief operating officer at Lilly shareholder Bahl and Gaynor. Retatrutide activates three hormone receptors - GLP-1, GIP and glucagon - earning it the nickname "triple G". Triple-G weight loss drugs are expected to produce greater weight loss than earlier generations by combining appetite suppression, blood sugar control and increased calorie burning. Rival Novo is also developing a "triple-G" weight-loss drug candidate UBT251 after securing global rights from China-based United Laboratories International as a follow-on to semaglutide, its highly popular drug sold as Ozempic and Wegovy. There have been significant investor expectations around retatrutide after mid-stage data demonstrated up to 24.2% weight loss after 48 weeks, surpassing results seen with other obesity drugs. Wegovy and Zepbound have been shown in trials to produce weight loss of about 15% and 20% or more. (Reporting by Sriparna Roy, Mrinalika Roy and Christy Santhosh in Bengaluru, additional reporting by Boleslaw Lasock; Editing by Sriraj Kalluvila)

Dive Brief:An experimental Eli Lilly obesity medicine helped patients lose more than a quarter of their body weight while offering relief from knee osteoarthritis in a Phase 3 study released Wednesday.Patients on the highest dose of retatrutide lost an average of 28.7% of their body weight after 68 weeks of treatment, compared with 26.4% on the lower dose and 2.1% on placebo, Lilly said. Additionally, 39% of patients on the highest dose achieved weight loss of 30% or more and 24% of those on that dose saw their weight drop by 35% or more, Lilly said.Lilly has now produced a drug with the best weight loss results of any medication to date, Leerink Partners analyst David Risinger wrote in a note to clients. Before the release, Risinger said he was looking for weight loss in the mid-high 20% range, which would surpass the effects seen with Lillys tirzepatide, the worlds best-selling drug, sold as Zepbound for obesity.Dive Insight:With the latest study, Lilly is putting the obesity field on notice again, Evercore ISI analyst Umer Raffat wrote in a note to clients. The trial, dubbed Triumph-4, isnt even the one designed to maximize weight loss; those results are due next year and will include data from treatment over 80 weeks, he added.The Triumph-4 study comes after a Phase 2 trial released in 2023 that wowed doctors and analysts. Lilly also has a number of other Phase 3 studies underway in obesity and diabetes and plans to issue seven readouts next year on the injectable drug. Lilly is now raising the bar for future tirzepatide competitors, Leerinks Risinger said.Retatrutide offers a new way to combat obesity, activating three different receptors in the body, GLP-1, GIP and glucagon. Novo Nordisks drug Ozempic, sold as Wegovy for obesity, also targets GLP-1, while Lillys Zepbound focuses on both GLP-1 and GIP.The Triumph-4 trial included patients who had a body mass index of at least 27, but the vast majority had a baseline BMI of 35 or more, Lilly said. For the average patient on the highest dose, losing 28.7% of their body weight translated to a loss of about 71 pounds. Carrying less weight by the end of the trial, more than two-thirds of all treated patients achieved a 70% reduction in knee arthritis pain. More than one out of eight patients on the drug said they were completely free of pain.There were side effects, mostly those that are often seen with the GLP-1 drugs. More than 43% of patients on the highest dose experienced nausea, about a third had diarrhea and a quarter reported constipation, Lilly said. About 21% endured vomiting. Additionally, 21% of patients on the highest dose suffered from a type of skin sensitivity known as dysesthesia. Evercores Raffat wrote that he wants to learn more about that finding.Overall, about 18% of patients taking the 12 mg dose dropped out of the study because of adverse events, compared with 12% of those on the 9 mg dose and 4% who were given a placebo. The discontinuation rates were highly correlated with a patients baseline BMI and included some patients who pulled out because they thought they were losing too much weight, Lilly said.The data offer Lilly another leg up in the increasingly competitive market for obesity treatments. The Indianapolis-based drugmaker recently became the first pharmaceutical company to hit a $1 trillion valuation and is looking to maintain its edge with new options such as an obesity pill called orforglipron its hoping to introduce in coming months.Meanwhile, a raft of companies are trying to improve on the offerings from market leaders Lilly and Novo. Metsera, recently the subject of a bidding war between Pfizer and Novo, in September showcased results from a drug that may require less frequent dosing. Multiple companies are advancing medicines to help patients taking weight loss treatments preserve muscle mass. And other drugmakers are investigating treatments that work in different ways or in combinations. '