The Big 2020 Challenge

Over the last three decades, the biotechnology industry has transformed our medicines cabinet, bringing new, effective treatments for a range of unmet needs, from rare genetic conditions, to stubborn cancers and debilitating chronic diseases. Yet several widespread afflictions remain woefully under-served. Alzheimer’s, Parkinson’s and other CNS afflictions are becoming more prevalent as societies age. Obesity, on the other hand, is shortening life-spans. 41 million people worldwide die prematurely each year from diabetes, heart disease and stroke – all tightly associated with obesity.

By the start of the next decade, half of all American adults will be obese. One in four will be severely obese. That’s according to a December 2019 analysis published in the New England Journal of Medicine. The authors analyzed reported body mass index (BMI) data from over 6 million adults, corrected it for self-reporting bias, and concluded that severe obesity is likely to become the most common BMI category among women, non-Hispanic black adults and low income adults.

It is clear from the handful of obesity drugs and products already on the market that obesity cannot be adequately addressed by medicine alone. Life-style changes are required alongside. Even then, weight-loss is slow, modest and often quick to reverse.

So most of the big biopharma players have stopped looking for obesity treatments. They’re instead trying to address the multitude of conditions associated with, and perhaps caused by, obesity. These include (but are not limited to) cardiovascular disease, diabetes, joint pain and inflammation, fatty liver disease and many types of cancer.

Novo Nordisk is among the most active players in obesity. Diabetes and obesity are often linked, and some of Novo’s diabetes drugs also promote weight loss. Saxenda (liraglutide) is already approved for chronic weight management; the company is running several late-stage trials designed to achieve an obesity label for its newest glucagon-like peptide-1 agonist, long-acting semaglutide (Ozempic). It is tough, though: approval requires very large trials and careful monitoring of cardiovascular outcomes, among other things. Safety is paramount: obese patients are not visibly ‘ill’. Like non-alcoholic steatohepatitis (NASH) and some kinds of heart disease, this is a silent, stealthy killer. Novo also has a partnership with Kallyope to develop new peptide-based drugs that work on the gut-brain axis, a promising and fast-evolving area of research.

The dream, according to Novo’s chief scientific officer Mads Krogsgaard Thomsen, is to come up with a drug “which does what bariatric surgery does, but in a simple, once-weekly injection.”

It’s still a dream. Meanwhile, Novo has moved into town-planning to help address both diabetes and obesity, with its five-year-old Cities Changing Diabetes program, a public-private partnership that includes University College London, the Steno Diabetes Center and authorities within over 20 global cities.

While most recent clinical trial developments in the industry’s meagre obesity pipeline have been under-whelming, scientific research continues into the cellular mechanisms behind obesity and its impact on other conditions. Excess fat does not only stress the cardiovascular system and the joints; fat cells secrete hormones and affect other cell growth regulators. Adipose tissue can become fibrotic, causing inflammation and damage to other organs, and resistance to insulin (hence the link between diabetes and obesity). It can alter the body’s metabolic control and energy storage functions in a vicious cycle, for instance making the body resistant to bariatric surgery and other more invasive efforts to combat obesity.

A deeper understanding of adipose tissue metabolism may catalyse a new generation of more effective drugs. But we can’t count on it. Addressing obesity requires a far broader, more concerted effort, among politicians and policy-makers, food and drink retailers, insurers, individuals and drug, device and technology firms. It is one of this decade’s biggest challenges.