GCGR

Novo Nordisk said its highly anticipated Phase 3 readout showed that CagriSema only managed 22.7% weight loss at 68 weeks, failing to hit the 25% benchmark the company, investors and analysts were seeking. The result was still a statistically significant benefit over the placebo group, in which the weight loss was 2.3%. These figures were based on a per-protocol analysis, evaluating the effects of CagriSema if all people adhered to treatment. Using an intent-to-treat analysis, which is generally regarded as more rigorous and is designed to measure the treatment effect regardless of discontinuation or use of rescue medication, CagriSema recipients lost just 20.4% of their weight, versus a loss of 3% on placebo. Just over 40% of CagriSema recipients lost at least a quarter of their body weight. The data likely mean that sales of CagriSema will not hit the hefty sales estimates bankers had made. Before the readout, Jefferies analysts said consensus forecasts for CagriSema’s peak sales were around $20 billion in diabetes and obesity combined. As soon as the data dropped, Novo’s stock $NVO crashed by as much as 26% pre-market Friday. By market open the share drop was 20%, representing a loss of around $100 billion in Novo’s market value. A Novo spokesperson told Endpoints News that the company plans to conduct a new trial of CagriSema in the first half of next year, using optimized dose titration. Novo gave few details on the product’s safety, saying only that it “appeared to have a safe and well-tolerated profile.” The most common side effects were gastrointestinal, the “vast majority” being mild to moderate and diminishing over time. There had been worries about gastrointestinal side effects ahead of the readout. CagriSema combines the amylin analog cagrilintide and Ozempic and Wegovy’s active ingredient semaglutide. According to Barclays analysts, the allure behind combining the two is that semaglutide increases insulin secretion and that amylin works alongside that to manage postprandial glucose levels. By targeting multiple energy balance-regulating pathways concurrently, the combo could enhance the magnitude and duration of weight loss. Similar thinking underlies Lilly’s development of tirzepatide, a co-agonist of GLP-1 and gastric inhibitory polypeptide (GIP). This was more effective than Wegovy, which acts on the GLP-1 receptor alone, in a recent head-to-head trial. The new CagriSema data are roughly on par with tirzepatide’s in its pivotal obesity trial. Lilly’s retatrutide, which acts on the GLP-1, GIP and glucagon receptors and is also subcutaneous, is in Phase 3. In a mid-stage test, this candidate allowed obese patients to lose nearly a quarter of their body weight after just under a year’s treatment. The pivotal trial of retatrutide in non-diabetic obese patients will assess weight loss at 80 weeks, and data are expected in 2026. Retatrutide’s safety will be watched closely. Among all the patients in the Phase 2 study, 8% discontinued treatment because of adverse events, higher than was seen with Wegovy or Zepbound in their trials. The late-stage CagriSema trial enrolled 3,417 patients and studied the shot at weekly flexible doses of up to 2.4 mg of each component. Separate arms assessed the same doses of cagrilintide and semaglutide alone, as well as placebo. By the end of the study, 57.3% of patients treated with CagriSema were on the highest dose. Novo did not say whether patients stopped increasing their doses because they were happy with their weight loss at a lower dose or because they could not tolerate higher doses. CagriSema did not undergo Phase 2 trials in obesity, though both its individual parts have separately been trialed in that indication. Novo put the combo straight into Phase 3 in 2022. But CagriSema did go through a Phase 2 test in patients with diabetes who were overweight and offered weight loss of 15.6% at 32 weeks. The components were tested individually in this trial too; semaglutide delivered 5.1% weight loss and cagrilintide 8.1%. The frequency of gastrointestinal adverse events almost doubled with CagriSema compared with each component alone, at 58% with the combo versus 32% with the GLP-1 and 33% with cagrilintide. Data from CagriSema’s second pivotal trial, in patients with both type 2 diabetes and obesity or overweight, should come in the next six months. Editor’s note: This article was updated throughout to add more detail to the story and chart, as well as to include a company comment on an additional trial.

GAITHERSBURG, Md., Dec. 19, 2024 (GLOBE NEWSWIRE) -- Altimmune, Inc. (Nasdaq: ALT), a clinical-stage biopharmaceutical company, today announced that it will be added to the Nasdaq Biotechnology Index (Nasdaq: NBI) effective prior to the market open on Monday, December 23, 2024. “Our addition to the NBI is an important recognition to conclude what has been a year of major progress for the Company,” said Vipin K. Garg, Ph.D., President and Chief Executive Officer of Altimmune. “With a number of significant inflection points coming in 2025, including the topline data from the Phase 2b IMPACT trial of pemvidutide in MASH in the second quarter, we believe that we are well positioned heading into the new year.” Established in 1993, the Nasdaq Biotechnology Index is designed to track the performance of a set of Nasdaq-listed securities that are classified as either Biotechnology or Pharmaceutical according to the Industry Classification Benchmark (ICB). Companies in the NBI must meet certain eligibility requirements, including market capitalization, average daily trading volume and seasoning. The Index is evaluated annually and serves as the basis for the iShares NASDAQ Biotechnology Index Fund (Nasdaq: IBB). For more information about the NASDAQ Biotechnology Index, visit: https://indexes.nasdaqomx.com/Index/Overview/NBI. About Pemvidutide Pemvidutide is a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonist in development for the treatment of obesity and MASH. Activation of the GLP-1 and glucagon receptors is believed to mimic the complementary effects of diet and exercise on weight loss, with GLP-1 suppressing appetite and glucagon increasing energy expenditure. Glucagon is also recognized as having direct effects on hepatic fat metabolism, which is believed to lead to rapid reductions in levels of liver fat and serum lipids. In clinical trials to date, once-weekly pemvidutide has demonstrated compelling weight loss with class-leading lean mass preservation, and robust reductions in triglycerides, LDL cholesterol, liver fat content and blood pressure. The U.S. FDA has granted Fast Track designation to pemvidutide for the treatment of MASH. Pemvidutide recently completed the MOMENTUM Phase 2 obesity trial and is being studied in the ongoing IMPACT Phase 2b MASH trial. About Altimmune Altimmune is a clinical-stage biopharmaceutical company focused on developing innovative next-generation peptide-based therapeutics. The Company is developing pemvidutide, a GLP-1/glucagon dual receptor agonist for the treatment of obesity and MASH. For more information, please visit www.altimmune.com. Follow @Altimmune, Inc. on LinkedIn Follow @AltimmuneInc on Twitter Company Contact: Greg Weaver Chief Financial Officer Phone: 240-654-1450 ir@altimmune.com Investor Contact: Lee Roth Burns McClellan Phone: 646-382-3403 lroth@burnsmc.com Media Contact: Danielle Cantey Inizio Evoke, Biotech Phone: 619-826-4657 Danielle.cantey@inizioevoke.com This press release was published by a CLEAR® Verified individual. Source: Altimmune, Inc

The battle for market share between the two leaders in the booming obesity drug sector has a new data point decidedly in favor of Eli Lilly. The Lilly drug Zepbound has topped Novo Nordisk’s Wegovy in a head-to-head clinical trial. According to the preliminary Phase 3b results, treatment with Zepbound led to 47% greater relative weight loss compared to Wegovy, Lilly announced Wednesday. The pharmaceutical giant said more details will be published and presented at a medical meeting next year. But these results provide evidence that a drug that hits two metabolic targets leads to greater reduction in weight, which could give Lilly an edge as it seeks gains in market share and insurance coverage of the blockbuster product. Zepbound’s main ingredient is a peptide engineered to bind to and activate two targets, the GLP-1 and GIP receptors. By contrast, Novo Nordisk’s Wegovy targets only the GLP-1 receptor. Both drugs are administered as once-weekly injections. Health IT Reducing Clinical and Staff Burnout with AI Automation As technology advances, AI-powered tools will increasingly reduce the administrative burdens on healthcare providers. By Dr. Michael Blackman, Chief Medical Officer at Greenway Health The head-to-head test enrolled 751 people in the U.S. and Puerto Rico with obesity or overweight as well as certain associated comorbidities, such as hypertension and cardiovascular disease. However, the study specifically excluded those who have type 2 diabetes. Participants were randomly assigned to receive Zepbound or Wegovy for 72 weeks. The main goal was to measure the percent change in body weight from baseline. Participants in the Zepbound cohort showed an average 20.2% loss in body weight, Lilly said. That translates to an average 22.8 kg (50.3 pounds) of weight shed. By comparison, those who received Wegovy lost an average 13.7% of their weight, or 15 kg (33.1 pounds). On a key secondary endpoint, Lilly said 31.6% of participants receiving Zepbound achieved at least 25% body weight loss. In the Wegovy arm, 16.1% of participants achieved that mark. “Given the increased interest around obesity medications, we conducted this study to help health care providers and patients make informed decisions about treatment choice,” Leonard Glass, senior vice president of global medical affairs at Lilly Cardiometabolic Health, said in a prepared statement. Lilly said the overall safety profile of Zepbound in the head-to-head study was similar to previous tests of its drug. This entire class of drugs that mimic gut hormones comes with gastrointestinal side effects that lead some patients to discontinue treatment. The Phase 3 clinical trial results that supported Zepbound’s FDA approval last year showed side effects such as nausea, diarrhea, and vomiting. Lilly said Wednesday that the most commonly-reported adverse events in Zepbound’s Phase 3 program were gastrointestinal and were classified as mild to moderate in severity. presented by Market Trends to Watch for Health Systems and Their Specialty Pharmacies The future looks bright for the integrated specialty pharmacy model – for health systems, providers, and most importantly, for patients. By Jake Gaffey, MBA, Chief Strategy Officer at Shields Health Solutions Zepbound has fast become one of Lilly’s top products. In the nine months ended Sept. 30, Lilly reported more than $3 billion in Zepbound sales. The latest clinical trial results should help Zepbound gain market share over Wegovy, Leerink Partners analyst David Risinger said in a Wednesday note sent to investors. But he pointed out that Lilly did not disclose a comparison of the tolerability of these medications, which could be another point of differentiation beyond the magnitude of weight loss. A cross-trial comparison of historical data from independent Phase 3 tests of each medication showed better tolerability for Zepbound compared to Wegovy, with the Novo Nordisk product posting higher rates of nausea and vomiting, Risinger said. He added that he’s looking forward to the publication and presentation of the head-to-head data in 2025 for more details on this comparison. There are other companies developing weight loss drugs that target both GLP-1 and GIP. Viking Therapeutics has reached Phase 3 testing with VK2735, a once-weekly injectable medication designed to activate both the GLP-1 and GIP receptors. Viking could stand apart from the field with an oral version, which last month posted encouraging Phase 1 data. Amgen is also going after both GLP-1 and GIP with a drug called MariTide. But one key difference with Amgen’s drug is that rather than activating the GIP receptor, the peptide antibody conjugate blocks this target. Last week, Amgen reported preliminary Phase 2 results showing MariTide achieved weight loss comparable to Lilly’s Zepbound. Amgen aims to differentiate with once-monthly or even less frequent dosing. Lilly isn’t settling for just two targets. It’s R&D efforts include retatrutide, a peptide engineered to hit GLP-1, GIP, and a third target — the glucagon receptor. Last year, Lilly reported Phase 2 results showing this triple mechanism achieved greater weight reduction than GLP-1 and GIP activation. Results were published in the New England Journal of Medicine. Retatrutide’s late-stage clinical development includes tests underway in obesity and type 2 diabetes. Photo by Eli Lilly