Big pharma hunts for weight-loss drugs without nasty side effects

{"text":[[{"start":8.36,"text":"Weight-loss drugs such as Mounjaro and Wegovy have been blockbusters for the Big Pharma groups that developed them."}],[{"start":14.36,"text":"But while the treatments have been hailed for transforming the often torturous process of losing weight for millions of people, the companies behind them have noted a problem: side effects."}],[{"start":24.14,"text":"Many patients report gastrointestinal side effects of incretin-based therapies, such as Eli Lilly’s Mounjaro and Novo Nordisk’s Wegovy, including nausea, constipation, diarrhoea and vomiting."}],[{"start":35.28,"text":"“Within 20 minutes of the first injection, I felt mild nausea,” said one London-based advertising executive, who took Mounjaro. Reports of side effects typically increase with higher doses but she experienced the symptoms even after starting out by microdosing, on just 0.25mg."}],[{"start":53.56,"text":"The executive kept a diary of her symptoms, which included pain and aches in her stomach, bad breath and burping. “If I had started on the higher dose, I would have felt sicker for sure,” she said."}],[{"start":64.6,"text":"Pharma groups are now working to develop therapies that can deliver similar weight loss while addressing many of the concerns with the current market leaders."}],[{"start":71.8,"text":"Associated benefits for new drugs could also include improving cardiovascular and liver health of patients and muscle mass preservation."}],[{"start":null,"text":"

"}],[{"start":79.56,"text":"Martin Holst Lange, Novo’s chief scientific officer who oversees research and development, said the current class of drugs had “transformed how we treat obesity today — but it is not enough to meet individual needs among a great number of patients”."}],[{"start":92.72,"text":"Most of the leading new drugs in development target receptors for amylin, a hormone secreted in the pancreas alongside insulin that works similarly to existing GLP-1 drugs, such as Wegovy and Mounjaro. While GLP-1s suppress appetite, amylin drugs bind to different parts of the brain to promote satiety — making people feel full faster."}],[{"start":null,"text":""}],[{"start":112.64,"text":"David Kendall, chief medical officer at Denmark’s Zealand Pharma, said amylin “amplifies the capacity to tell you that you’ve had the food experience and have had enough”."}],[{"start":121.76,"text":"GLP-1s, by contrast, leverage “food aversion signals” that are “effective” but not natural to how the human brain typically behaves, he said. “While amylin can have similar effects [to GLP-1s], it does not have identical effects both on the brain and on side effects.”"}],[{"start":139.44,"text":"Zealand is developing petrelintide, an amylin-based candidate, in conjunction with Swiss giant Roche, which licensed it last year in a deal worth up to $5.3bn."}],[{"start":150.12,"text":"Results of a mid-stage trial reported in March showed that patients lost 10.7 per cent of their body weight on average after 42 weeks of treatment. Side effects were similar to those of a placebo and the company said there were no cases of vomiting or discontinuation of treatment due to gastrointestinal issues, even at the maximum dosage."}],[{"start":168.76,"text":"However, despite the positive news on side effects, the fact that the weight loss was lower than that achievable with existing drugs — up to 25 per cent of body weight — sent shares in the Danish biotech down a third after the results were announced."}],[{"start":183.12,"text":"Roche and Zealand have nevertheless advanced the drug to a phase 3 trial. Kendall said the lack of major gastrointestinal issues for participants “portends a better long-term experience” for people taking the drug."}],[{"start":null,"text":""}],[{"start":195.32,"text":"Yet reducing side effects is not the only reason pharma groups are trying to create the next generation of weight-loss drugs. For incumbents such as Novo and Lilly, patent expiries are looming, making it crucial for their business strategies to develop new therapies before the end of this decade."}],[{"start":211.4,"text":"Novo’s semaglutide has already lost patent protection this year in Canada, India, China, Brazil and Turkey. Concerns over the state of the company’s pipeline contributed to the ousting of Novo’s chief executive last year."}],[{"start":224.6,"text":"One candidate being trialled by Novo is CagriSema, another amylin-based drug. Patients in a CagriSema study lost an average of 22.7 per cent of their body weight. Novo submitted CagriSema to the FDA for regulatory approval in December."}],[{"start":240.36,"text":"Lange, Novo’s science chief, said CagriSema addressed the “two different receptor systems”, meaning it combines the two pathways in which amylin and GLP-1 drugs work using a fixed dose combination."}],[{"start":252.66,"text":"He said this would allow Novo to focus on patients who not only wanted to lose larger amounts of body weight but also on comorbidities. While existing drugs have yielded often unexpected extra health benefits, the new breed will specifically target them."}],[{"start":null,"text":""}],[{"start":266.84,"text":"Novo is also developing oral and injectable versions of amycretin — a similar combination of amylin and semaglutide. Patients lost an average of 24.3 per cent of their body weight on the highest injectable dose in trial results reported last year."}],[{"start":281.6,"text":"Other formulations are in the works. Lilly said clinical trial data for a new retatrutide drug shows that it can reduce food consumption, speed up metabolism, promote maintenance of energy expenditure during weight loss and also reduce inflammation."}],[{"start":295.6,"text":"Patients who used the drug lost 28 per cent of their body weight on average after 80 weeks at the highest dose — the largest delivered by any medicine so far, although patients discontinued at a higher rate (11 per cent) due to side effects."}],[{"start":308.96,"text":"Experts say weight-loss treatments will probably follow diabetes care where there are multiple options for patients in the long term, enabling people to, in effect, design their own pathways."}],[{"start":318.86,"text":"Patients may always have to endure the gastrointestinal side effects of weight-loss medicines since these drugs alter the normal digestive process, but they could become milder with the new formulations."}],[{"start":328.94,"text":"“It is possible that medicines that target different biological pathways might lead to more side effects and the clinical trials will identify the most common side effects,” said Katrina Bicknell, professor of pharmacology at the University of Reading."}],[{"start":342.44,"text":"But she added that combination medicines that targeted different pathways could allow people to take lower doses of weight-loss drugs that would reduce unpleasant side-effects."}],[{"start":350.88,"text":"“This is where combination medicines might offer an advantage,” Bicknell said. “Medicines that target different pathways . . . might mean that lower doses of individual drugs can be taken, reducing [the] risk of unpleasant side effects whilst achieving equivalent weight-loss results.”"}],[{"start":369.9,"text":""}]],"url":"https://audio.ftcn.net.cn/album/a_1787123866_6258.mp3"}