One of the biopharma industry’s marvels of the 2020s has been the enormous medical and financial success of the GLP-1 class of drugs. But the path to commercialization of these therapies was far more complex than most understand, and some of the earliest history has never been presented.
Beginning in 1988, I was part of what I believe was the earliest commercial effort to develop GLP-1 as a metabolic therapy. Despite extremely promising results, Pfizer, the major funder of the work in alliance with California Biotechnology, abandoned the effort around 1991 after mistakenly concluding that the GLP-1 therapeutic approach was not worth continuing. To be clear, I’m not writing this to claim credit for discovery or development of GLP-1s or anything like that. Rather, I think the story offers valuable lessons on drug development for pharmaceutical companies, researchers, and the general public alike.
In 1987, John Baxter — a professor of medicine at UCSF, leader in molecular endocrinology, and founder of a biotech firm named California Biotechnology — asked me to work with him to create a start-up focused on metabolic disease, and I enthusiastically agreed. I enlisted two Harvard colleagues, Ron Kahn and Bruce Spiegelman, and together we outlined an approach that included a search for novel insulin analogues and insulin sensitizing agents, identifying the protein responsible for obesity in genetically obese mice (six years before identification of the ob gene), and exploration of gut factors regulating metabolism, such as the “incretins” that enhanced insulin secretion.
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