Regeneron, AZ team up on drugs for obesity “superpower” gene

AstraZeneca has formed a partnership with Regeneron to investigate the potential of treating obesity using drugs directed at GPR75, a protective gene identified by scientists at the Regeneron Genetics Centre.

AZ’s buy into the programme comes a few weeks after Regeneron published findings in the journal Science suggesting that people with certain GPR75 mutations have 54% reduced risk of obesity, based on sequencing data from almost 650,000 people in the US, UK and Mexico.

The study found that individuals who have at least one inactive copy of the GPR75 gene have lower body mass index (BMI) and tend to weigh around 12 pounds less than those without the mutation.

AZ and Regeneron will collaborate on finding small-molecule drugs directed against the GPR75 target, splitting the costs of the programme and sharing any resulting profits from the endeavour.

When the GPR75 researh was published, Regeneron’s chief scientific officer George Yancopoulos, described the mutations as a “genetic superpower” that “provides hope in combating global health challenges as complex and prevalent as obesity.”

The protective effect has been validated in animal studies which found that mice genetically engineered to lack copies of the GPR75 gene gained 44% less weight than mice without the mutation when both groups were fed a high-fat diet.

The GPR75 mutation has also been linked to improvements in metabolic parameters, including glucose lowering, which puts the programme firmly in AZ’s wheelhouse given its focus on diabetes with drugs like its blockbuster SGLT2 inhibitor Farxiga/Forxiga (dapagliflozin).

At the moment AZ’s clinical-stage pipeline only lists one candidate for obesity, its large-molecule GLP-1/glucagon dual agonist cotadutide which has reached mid-stage testing for overweight and obesity in diabetics, chronic kidney disease associated with type 2 diabetes, and non-alcoholic steatohepatitis (NASH).

Drugs to treat obesity have struggled to make headway in recent years, leaving the category largely untapped, but there are signs of change.

Novo Nordisk’s once-daily injectable weight loss therapy Saxenda (liraglutide) has been a slow grower, but is on a blockbuster trajectory with first quarter sales topping $250 million. Meanwhile, follow-up GLP-1 agonist Ozempic (semaglutide) has shown encouraging results in a phase 3 trial, and its once-weekly dosing may encourage greater take-up.

Novo Nordisk applied to the FDA for approval of semaglutide in obesity in December, using an acquired priority voucher to speed up the review time. Looming on the horizon is Lilly’s tirzepatide, which has posted impressive weight-loss data in diabetes and is in phase 3 for obesity.

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