CagriSema

Within the pharmaceutical industry, a multibillion-dollar race is underway to top Novo Nordisks and Eli Lillys in-demand obesity drugs.Dozens of companies, large and small, have set out to test experimental medicines they claim could be more potent, convenient or have fewer side effects than Novos Wegovy and Lillys Zepbound. But those two companies are already hard at work with successors of their own.The next six months figure to be an important preview. Data are expected for a number of drugs that are already, or are shaping up to be, contenders in this high-stakes competition. The readouts will be closely watched, as they will set expectations for how the obesity drug market currently a duopoly between Lilly and Novo will look in the future. Heres what to expect:Zepbound versus WegovyHead-to-head trials always carry high risk. Any company that sponsors one is doing so with the knowledge testing could reveal its drug is equivalent to a competitor or, worse, less effective.With Zepbound, Eli Lilly appears to believe its a risk worth taking. In a trial called SURMOUNT-5, Lilly enrolled 700 people in an attempt to prove Zepbound is better than Wegovy at reducing the body mass of people with obesity or who are overweight, and have another weight-related complication like heart disease or high blood pressure.It expects to have results by the end of the year, and the findings could impact physician and patient perception of which drug offers greater weight loss benefits..So far, Zepbound has seemed superior, as testing showed treatment helped people with obesity lose up to 21% of their body weight. The comparative figure for Wegovy was 16% in the Phase 3 trials Novo used to gain Food and Drug Administration approval. Based on this, Leerink Partners analyst David Risinger expects Zepbound to show a statistically significant advantage in the head-to-head trial.A resoundingly positive outcome could help push Lilly past $1 trillion in market valuation, a milestone that would be a first among pharmaceutical firms. Lilly is currently worth nearly $900 billion.Yet Lilly has yet to prove Zepbound can prevent cardiovascular complications in people with obesity or who are overweight and already have heart disease, as Novo has with Wegovy. That study result helped Novo gain limited Medicare coverage for people with existing heart disease. Lilly has an outcomes trial called SURPASS-CVOT underway, but doesnt expect to have data until next year.Novos dual agonistWegovy works by stimulating a metabolic hormone called GLP-1, while Zepbound targets GLP-1 and a second one called GIP. The biology behind the dueling approaches is still being sorted, but Zepbounds dual agonism has set a model for others to follow, including Novo.The Danish company is now in late-stage testing with a dual-acting experimental drug it calls cagrisema. The drug combines semaglutide, the active ingredient in Wegovy, with another compound that mimics a metabolic hormone called amylin.Cagrisemas Phase 3 trial, called REDEFINE1, is due to wrap up and generate data in the fourth quarter. The results could help Novo fight off Lillys commercial challenge should SURMOUNT-5 favor Zepbound over Wegovy.REDEFINE1 tests cagrisema against a placebo and Wegovy, measuring weight loss over 68 weeks in about 3,400 people. Cagrisemas performance against Wegovy should give analysts a sense of how well it might also measure up against Zepbound, once the SURMOUNT-5 data are available.Novo is also testing cagrisema directly against Zepbound, but that trial isnt due to generate data for another year.Amgens contenderAmgen isnt known for cardiometabolic drugs, but it has one, called maridebart cafraglutide or maritide, thats among the most closely-watched obesity medicines not owned by either Lilly or Novo.Maritide targets the same two gut hormones, GLP-1 and GIP, that Zepbound does. But, somewhat controversially, it is designed to inhibit rather than stimulate GIP. It is also a monthly shot, compared with the weekly injections used for Wegovy and Zepbound.Phase 2 results for maritide are due by the end of the year. Enthusiasm for the experimental drugs potential has driven Amgens shares higher this year sometimes dramatically so. Phase 1 data Amgen disclosed in February suggested it might drive the most weight loss among tested drugs over 12 weeks, according to Stifel analysts.The Phase 2 trial enrolled nearly 600 people with obesity, some of whom also have diabetes, and randomized them to receive one of several doses of maritide or a placebo. Researchers will measure weight loss over 52 weeks.An obesity pillNovo has advanced an oral version of Wegovy and Lilly has pushed its pill oforgliproninto Phase 3 trials. But there are many rivals staking their competitive future on the idea that people with obesity will prefer a pill over a shot. Roche is one such company, having acquired Carmot Therapeutics for $2.7 billion in late 2023 to gain access to three obesity drugs.A Phase 1 dosing trial of the GLP-1 pill CT-996 is due to wrap up by November, which will give Roche and its investors an idea of the drugs biological activity, safety and weight loss. Roche already reported data from earlier stages of the trial, which tested single and increasing doses in trial volunteers who are overweight or have obesity. The third part will test the pill in 60 people who have diabetes in addition to obesity or being overweight.Roche has already said CT-996 will advance into Phase 2 clinical development based on the Phase 1 data. Its already touting the drugs best-in-class potential, although Phase 2 data will be a better test of that claim. Others are already in Phase 2, including Pfizer with its drug danuglipron and Structure Therapeutics with GSBR-1290. They could soon be joined by Terns Pharmaceuticals TERN-601 and Viking Therapeuticsoral version of VK2735.Preserving muscle massThe rapid weight loss stimulated by GLP-1 agonists melts away muscle as well as fat. That worries some experts, who note how people who discontinue treatment tend to regain weight in the form of fat. Muscle cells also have a higher resting metabolic rate, which results in higher caloric burn.In response, some drugmakers are exploring ways to preserve lean muscle mass. An early test could come in the form of results for Verus enobosarm, a type of drug that stimulates muscle-building hormones. Previously sold under the name Ostarine, it has been tested clinically in people with cancer whose muscles have shrunk, as well as those with muscular dystrophy.In obesity, a Phase 2 test of enobosarm together with Wegovy is underway in people 60 and over who are overweight or have obesity and have lost muscle mass. The trial will measure how much trial volunteers muscle mass changes over 16 weeks, and will compare results in people who receive the two drugs to those who were given only Wegovy. Another endpoint will assess physical function by evaluating how participants climb stairs.Veru expects results by the end of the year. The data could help analysts parse how important lean mass might be in future obesity treatment.A new drug targetOutside of targeting GLP-1, GIP, amylin and other gut hormones, there are a range of other treatment approaches under evaluation. One involves blocking a cannabinoid receptor called CB1 that is known for regulating an appetite-modulating hormone called leptin. CB1 is known to have effects on other biological functions such as inflammation, too.So far, theres been at least one disappointing data point on CB1 inhibition. Phase 2 data for a Novo drug called monlunabant didnt meet expectations for weight loss, leading Novo to state that further work is needed to determine the optimal dosing.The next shot for CB1 may be Skye Biosciences nimacimab, which is due to have interim Phase 2 results by mid-2025. The trial, called CBEYOND, tests nimacimab against placebo, as well as a combination of Wegovy and nimacimab against Wegovy alone. The study will measure weight loss over 26 weeks. Enrolling 120 volunteers, the study should be large enough to detect at least an 8% difference between the experimental drug and placebo, according to the trials plan.Skye shares fell by more than 40% the same day Novo reported its data for monlunabant. '

Novo Nordisk announced on Wednesday that its new experimental weight loss drug Amycretin showed good safety and tolerability in preliminary trials, with only mild to moderate adverse effects. The maker of diabetes treatments Wegovy and Ozempic reported in March that its oral insulin mimics reduced body weight by 13.1 percent over 12 weeks in a phase I trial, sending its shares up more than 8 percent. In contrast, Wegovy lost about 6 percent of her body weight after 12 weeks and 15 percent after 68 weeks in a similar trial. Novo Nordisk presented full data from the phase 1 study at the European Association for the Study of Diabetes conference, and the company's shares were up 2.4 percent by 1307 GMT. "During the study period, we observed a 13.1 percent weight loss and side effects comparable to those of incretin based treatments, mainly gastrointestinal side effects," Martin Holst Langer, head of research and development at Novo Nordisk, said in an interview ahead of the meeting. According to data presented at the meeting, one serious but non-fatal adverse event was reported in the 60-participant trial. There were no reports of serious side effects among those taking Amycretin, but a total of 242 mild and moderate side effects were reported. Amycretin is designed to mimic the GLP-1 gut hormone modelled by Wegovy, and also affects the hunger pancreatic hormone amylin. Novo Nordisk said Amycretin's side effects, mainly related to gastrointestinal discomfort, including nausea and vomiting, were similar to other drug trials in the same GLP-1 drug class. The company is also developing another two-drug combination called CagriSema, which also targets the pancreatic peptide hormone, which Novo Nordisk says has the potential to lead to a 25 percent weight loss. "The data I've seen so far suggest that pancreatic enzyme has at least the same weight loss potential as CagriSema," Lange said. Novo Nordisk said that in the study, overweight or obese patients without diabetes received gradually increasing doses of Amycretin, starting with 3 milligrams and ending with two 50-milligram pills. At the end of the 12-week trial, patients taking 50mg of Amycretin lost an average of 10.4 percent of their body weight, while those taking the maximum dose of 2x50mg lost 13.1 percent. After 12 weeks, weight loss did not plateau. In comparison, those taking the placebo lost an average of 1.1 percent of their body weight. Lange believes these data warrant further clinical investigation. Next year, once data from an early study of a subcutaneous version of the drug is ready, a decision will be made on whether to skip the Phase II trial and go straight to Phase III - usually the final stage before seeking approval. Existing weight-loss drugs such as Wegovy and Eli Lilly's Zepbound are injectable. Pills require a large number of active ingredients, which makes them more expensive to produce but often favored by patients. Both companies are racing to increase the active ingredient needed to make the much-needed GLP-1 weight-loss drug. Novo Nordisk shares have more than quadrupled since launching Wegovy in the United States in June 2021, but have fallen 15 percent since peaking in June this year. Analysts at Berenberg said last week that about 40 percent of Novo Nordisk's valuation depends on the experimental drugs it has in development. Last year Novo Nordisk became Europe's most valuable listed company, ahead of LVMH.