Weight loss drug candidates multiply, spurring hopes of lower costs

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New data on weight loss drugs that could compete with Novo Nordisk’s Wegovy are raising expectations there will soon be more options, and possibly lower prices, in an estimated $100 billion marketplace, doctors and pharmaceutical executives say.

Drugmakers are ratcheting up their research and aiming for new formulations that can be taken as pills, options to deliver higher weight loss or drugs that reduce fat while maintaining muscle.

“It has really been an explosion of innovation,” said Dr. Robert Gabbay, chief science officer at the American Diabetes Association (ADA), which receives funding from both Novo and Eli Lilly and Co and just concluded its annual meeting in San Diego, California. “If there are multiple (treatments) in the market, that will lead to some level of competition and greater access.”

Wegovy and Lilly’s Mounjaro were originally developed for type 2 diabetes. They are part of a class of drugs known as incretins designed to mimic the action of the GLP-1 hormone, which helps regulate blood sugar, slow the rate at which the stomach empties of food and decrease appetite.

Wegovy was approved for obesity in 2021 after studies showed that it led to 15% weight loss over 68 weeks, while Mounjaro, which demonstrated weight loss of more than 22% over 72 weeks, is expected to be authorized later this year.

At the ADA conference, Novo presented data from late-stage trial of a high-dose oral version of Wegovy showing similar weight loss results to the injected form when used alongside diet and physical activity, compared with 2.4% for a placebo.

“It’s all about options,” said Mico Guevarra, medical director at Novo. “What are your patient’s needs and goals? Let’s pick something that works for you.”

Lilly said the highest dose of its experimental pill orforglipron led to 14.7% weight loss after 36 weeks in a mid-stage trial of people who were obese or overweight.

“We are also thinking about worldwide needs and those patients that just don’t want an injectable,” said Lilly Senior Vice President Jeff Emmick.

Lilly also presented data from a mid-stage trial of its next-generation “triple g” injected drug retatrutide, which activates receptors for three hormones, showing that it led to mean weight reduction of up to 24.2% after 48 weeks.

A drug that can safely deliver 25% weight loss would represent a new milestone in treatment, getting patients closer to the outcomes achieved by invasive bariatric surgery.

“One of the things we know about bariatric surgery is that there’s a strong relationship between that amount of weight loss and improvement in a number of co-morbidities: cardiovascular outcomes, sleep apnea,” said Lilly’s Emmick.

Lilly’s Phase 3 trial program for retatrutide will include measuring the drug’s impact on things like sleep apnea and arthritis.

Pfizer earlier this week said it had discontinued work on experimental once-daily obesity pill lotiglipron, after liver safety issues were seen in clinical studies. The company said it would continue to develop its twice-daily weight loss drug candidate.

Structure Therapeutics is developing oral obesity drugs that it says are simpler to manufacture than the current injectables.

“The opportunity exists for better pricing. Accessibility is really important to us,” Structure CEO Ray Stevens said.

Zealand Pharma and Boehringer Ingelheim said their experimental obesity treatment was shown to reduce body weight by close to 19% in a mid-stage trial when looking at participants who had reached the intended dosage level for the injected medication.

Versanis Bio is working on drug called bimagrumab, licensed from Novartis, that is designed to block proteins from binding to receptors believed to inhibit muscle growth and promote fat accumulation.

“We define weight loss quality as the percentage of weight loss attributed to fat loss,” said Versanis Chief Scientific Officer Lloyd Klickstein. “With diets, bariatric surgery, incretin drugs or other weight loss drugs, two-thirds to three-quarters of the weight loss is fat, but one-quarter to one-third is lean.”

Drugmakers anticipate that data from upcoming trials designed to show that weight loss from GLP-1 drugs has a significant impact on cardiovascular outcomes will help convince health insurers to loosen any reimbursement restrictions.

So far, however, there is not a lot to differentiate between GLP-1 drugs – a situation that can help insurers when it comes to seeking price discounts in exchange for health plan coverage.

That is “where we have the opportunity to use our negotiations to drive lower costs because we need it to be a competitive category,” said Sree Chaguturu, chief medical officer at CVS Health, which owns health insurer Aetna.

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