Rising obesity rates, and associated complications like diabetes and heart disease, have sparked a hunt for drugs that can help people lose more weight than they typically can with lifestyle changes alone. A decade ago, a three-way race emerged between the weight-loss pills Contrave, Qsymia and Belviq, but each of them showed modest benefits and had side effects — Belviq was withdrawn because of an elevated risk of cancer.
On the injectable side, Saxenda is a high-dose version of Novo’s diabetes drug Victoza. Ozempic, a follow-on to Victoza, likewise has an approved formulation for obesity called Wegovy. And Novo’s rival Eli Lilly is looking for similar success with its experimental diabetes drug tirzepatide, which is now in clinical trials for obesity.
AstraZeneca and Regeneron are going with a different approach. They aim to develop a “small molecule” alternative to Novo’s and Lilly’s peptide drugs, meaning the product could be administered as a pill rather than an injection, which could make it more attractive to patients.
Regeneron’s genetics center identified five genes, including GPR75, that encode proteins expressed in portions of the brain that regulate hunger and metabolism. A mutation to GPR75, expressed in about 4 in every 10,000 people sequenced, was associated with a 54% reduction in the risk of obesity.
Regeneron tested the hypothesis by genetically altering GPR75 in mice, and found that it led to reduced weight gain when the mice were fed a high-fat diet.
The partnership will break new ground in two ways for Regeneron. A successful small molecule drug would be a first, since its marketed products are all biologics. Regeneron also doesn’t have a presence in metabolic disease — just two cholesterol-lowering agents, Praluent and Evkeeza, the former of which is partnered with Sanofi.
Collaborating with AstraZeneca could be seen as a sensible move, since the U.K. pharma giant has small-molecule expertise as well as an established presence in metabolic disease because of its diabetes drugs Farxiga and Onglyza.