Weight-loss drugs in development aim to replace injections with pills

By Eleanor Laise

Promising results for investigational weight-loss treatments and new screening recommendations for fatty-liver disease emerge from diabetes conference

Wall Street's obsession with next-generation obesity and diabetes treatments intensified over the weekend as drugmakers presented new clinical-trial data on the drugs -- including weight-loss pills in development that could become alternatives to popular injectables like Wegovy and Ozempic.

A once-daily, high-dose pill version of semaglutide, the medicine in Novo Nordisk's (NOVO-B.KO) Wegovy and Ozempic, resulted in 15.1% weight loss when used in combination with diet and exercise in adults with obesity or overweight and without type 2 diabetes, according to data released Sunday at the American Diabetes Association's annual scientific conference.

Eli Lilly's (LLY) orforglipron, another once-daily pill, achieved up to 14.7% average weight loss at 36 weeks in adults with obesity or overweight, according to data shared at the ADA conference.

Pfizer (PFE), meanwhile, said Monday that it would advance its danuglipron investigational pill for obesity and type 2 diabetes toward late-stage development but will terminate development of a similar treatment, lotiglipron, after early clinical data showed potential for elevated liver enzymes in some patients.

A key advantage of oral weight-loss drugs is "increased accessibility of these revolutionary drugs for people who have struggled to lose weight," Dr. Robert Gabbay, the ADA's chief scientific and medical officer, said in a statement. "The studies presented at this year's annual meeting are game changers in the way we customize treatment for individuals with obesity and those with type 2 diabetes."

More than half of Americans are concerned about their weight, and 50% are interested in taking weight-loss drugs, according to a recent survey by health news organization Stat and the Harris Poll, a market-research and consulting firm. Nearly half of the U.S. adults surveyed said they would spend up to $100 a month on such medications.

Several of the pills in development are GLP-1 receptor agonists, which can mimic the effects of a gut hormone that helps control appetite and blood-sugar levels -- the same basic mechanism that powers the injectable medications Wegovy, Ozempic and Mounjaro. Demand for those injections has been so strong that supplies have at times run short, and the U.S. Food and Drug Administration has warned patients against using knockoff compounded versions of semaglutide, which may contain different active ingredients than are used in the approved drugs.

Eli Lilly's tirzepatide, already FDA-approved as Mounjaro for people with type 2 diabetes, also produced average weight loss of 15.7% at the highest dose in adults with obesity or overweight and type 2 diabetes, according to study data released at the diabetes conference. "Lilly management knows how to build a moat, which is growing around Mounjaro," and the company's metabolic franchise broadly, given the "wall of data" on efficacy, tolerability, cross-trial comparisons and other data that set it apart from the competition, BMO Capital Markets analysts said in a research note Sunday. Lilly shares are up 23% in the year to date, while the S&P 500 is up 13%.

Investors punished Pfizer shares on Monday, sending the stock down 4% by midday. Despite the lotiglipron setback, Pfizer can remain competitive with its progress on danuglipron, BMO Capital Markets analysts said in a report Monday.

Promising results on treatments for type 1 diabetes also emerged from the conference, with Vertex Pharmaceuticals (VRTX) announcing data from a small trial of its VX-880 investigational therapy on Friday. All patients receiving the therapy produced endogenous insulin and had improved glycemic control while reducing or eliminating insulin use, the company said in a release.

The ADA's new recommendation, released Sunday, that adults with type 2 diabetes or prediabetes be screened for nonalcoholic fatty liver disease is also a boost for companies developing treatments for that condition, analysts said. Companies including Madrigal Pharmaceuticals Inc. (MDGL), Akero Therapeutics Inc. (AKRO) and 89bio Inc. (ETNB) are developing treatments for fatty-liver diseases, and the ADA recommendation is "another positive for the field," Evercore ISI analysts wrote in a report Monday.

-Eleanor Laise

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06-27-23 0811ET

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