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Drug Discovery

Regeneron, AstraZeneca partner to develop obesity drugs

The firms’ target is a protein that is mutated in people who weigh less

by Megha Satyanarayana
July 29, 2021 | A version of this story appeared in Volume 99, Issue 28


AstraZeneca and Regeneron Pharmaceuticals are partnering to develop small-molecule weight loss drugs based on the discovery of a possible new target by Regeneron’s genetics research group.

A person on a scale.
Credit: Shutterstock
A study found people with certain mutations in GPR75 were, on average, about 12 lbs lighter.

Neither company has developed a drug that directly treats obesity, though AstraZeneca has a fairly deep pipeline of drugs to treat obesity-related illnesses such as diabetes and heart disease. Any small molecules the companies successfully develop could earn them a piece of what Fortune Business Insights predicts will be a $3 billion worldwide market by 2027.

The terms of the deal were not disclosed, but in a press release, Regeneron says the companies will equally share in both development costs and profits that come out of the partnership.

“It’s the condition that has the highest unmet need among the various diseases we have globally,” says Regeneron scientist Luca Lotta of obesity. He led the research team that discovered the new obesity-related target.

Obesity has been a challenging disease to treat pharmacologically. The US Food and Drug Administration has approved 10 drugs targeting an array of metabolic and nervous system processes. But Lotta notes that some come with considerable side effects or have a modest effect on weight loss.

“It doesn’t have the same dramatic effect as, for example, bariatric surgery has,” he says of weight loss drugs. “Some patients tend to lose compliance over time.”

Several obesity drugs were developed to treat other diseases, including the recently approved Wegovy (semaglutide) and Saxenda (liraglutide), which was approved in 2014. The drugs are peptides that were first approved to treat diabetes. Both drugs are made by Novo Nordisk; sales of Saxenda were nearly $890 million in 2020.

Despite the prevalence of obesity in the US, the US Government Accountability Office reports that few Americans take obesity drugs, due in part to lack of insurance coverage.

The protein that Regeneron and AstraZeneca will try to drug, GPR75, is a member of the G-protein-coupled receptor family. To find it, a team of academic and industry scientists scanned the genomes of 640,000 people who are being tracked as part of long-term health studies, looking for genes in which rare variations are associated with either a low or high body-mass index. They discovered variations in 16 genes, including GPR75 and several others associated with the brain. Lotta says the brain connection is fascinating.

“The brain is an area that controls appetite or physical activity or food preference behaviors,” he says, noting that other obesity drug targets are also centered in the brain and central nervous system. Their search also uncovered other possible drug targets for obesity.

While it’s not completely clear how GPR75 affects weight, the research team found that people who couldn’t make a normal amount of the protein were, on average, about 12 pounds lighter than people who did. They were also significantly less likely to become obese.

When the research team reproduced the GPR75 gene defect in mice fed a high-fat diet, it found that the mice were thinner and had better control over their blood glucose levels. Lotta says the team still has a lot of work to do to characterize GPR75, and Regeneron would not say if any of the other genes that turned up in its search might also be future drug targets.


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