In the era of blockbuster obesity drugs, a personalized approach could boost outcomes
The recent success of diabetes and weight loss drugs like Ozempic and Wegovy demonstrates the power of clinical results in a market with vast unmet need. While many have shed pounds with the help of these GLP-1 agonists, the reality is that obesity is more complex and less monolithic in the kinds of therapies and lifestyle changes that work for individual patients.
Mark Bagnall, CEO, Phenomix Sciences
Permission granted by Phenomix
That’s why diagnostics to determine a patient’s obesity “type” would not only help physicians understand the disease more clearly but also usher in a new era of personalized medicine that reflects the innovations happening in areas such as cancer, said Mark Bagnall, CEO of obesity phenotyping startup Phenomix Sciences, which has released tests for two of the most common types of obesity.
Founded by two Mayo Clinic researchers, Phenomix has shown that phenotyping — finding the manifestations of genetic differences — for patients with obesity can make a difference in weight loss. The method has doubled the number of patients who respond to treatment and also doubled the amount of weight lost, according to the company’s published research.
“Like a lot of different areas of medicine, we’re finding that people are different — big surprise — and as a result, they respond differently to different interventions,” Bagnall said. “And 10 years of NIH-sponsored research into quantitative measures of obesity determined that 85% of patients have fundamentally four different subtypes or phenotypes of obesity.”
These four types differ mechanistically and require varying treatments for the best results, he said.
“Cancer therapy … has gotten to the point of a really granular level of understanding,” Bagnall said. “Obesity may get to that granular level eventually, and this is a breakthrough.”
After running reams of data through machine learning analysis and artificial intelligence bioinformatics systems, Phenomix developed a test that could fit into a normal doctor visit and determine which of the four types of obesity a patient has, making certain treatments more likely to help.
Four corners
The first obesity type the Mayo Clinic identified, “hungry gut,” is characterized by patients snacking between meals. These are patients who are most likely to respond best to GLP-1 drugs like Wegovy, Bagnall said.
The second is called “hungry brain,” and these patients tend to feel hungry shortly after eating. Together, these two types make up about 60% of obesity patients, and treatment for each can vary widely. While “hungry gut” patients might benefit from Novo Nordisk’s Wegovy, with a list price of about $1,600 per month, patients with “hungry brain” may respond better to an appetite suppressant called Qsymia from Vivus for a list price of $150 per month, Bagnall said.
“Beyond saving money, you’re getting a drug that’s more appropriate,” he said.
Phenomix has launched two separate tests under the MyPhenome moniker for hungry gut and, most recently in June, hungry brain.
The third type is “emotional hunger,” which Phenomix characterizes as eating in response to emotional triggers. For these patients, a drug like Contrave from Currax is more likely to spur weight loss, Bagnall said.
“If you only get 20% of the market, but it’s the right 20% of the market, you’re going to dominate that part.”
Mark Bagnall
CEO, Phenomix Sciences
A fourth type is a reduced metabolism called “slow burn,” and there is currently no specific treatment, though some companies are targeting mitochondria in the cells to increase efficiency.
“In two to three years, we’ll have drugs for each of these categories, as well as devices and surgical techniques associated with different phenotypes,” Bagnall said. “And there are lifestyle and diet interventions for each of the phenotypes that can also achieve results.”
Despite distinct genetic and physical differences between the obesity types, there is also significant overlap. But understanding where a patient fits in the spectrum would help physicians curate a weight loss program that works, Bagnall said.
‘No silver bullet’
The reality of the obesity market is that patients want to try the newest drugs that are working for others, but Bagnall said he’s seen treatments come and go without staying power.
“In the late ‘90s, a drug called Redox was introduced, and it was the same thing — all of a sudden, everybody was looking to get the stuff, and that’s just a human need to (find) a silver bullet,” Bagnall said. “And we’re at the silver bullet stage of obesity where a new drug is being sought after.”
Phenomix released its tests to the obesity specialist market in 2021 to combat this kind of monolithic thinking.
“If you’re an obesity specialist, you’ve seen enough patients to know that it’s not that simple,” Bagnall said. “Thank goodness for Novo for bringing such an effective drug into a problematic area, but finding the right patients is equally important.”
With the right diagnostic ensuring that patients taking Wegovy are the ones best suited for it, the average weight loss per patient would improve, he said. And those dynamics are starting to affect the market potential of specific drugs.
“There’s a realization within the drug companies when they see the number of drugs in development with different mechanisms addressing different elements of obesity, that there’s going to have to be a tool to sort out which patients get the right drugs,” Bagnall said. “If you only get 20% of the market, but it’s the right 20% of the market, you’re going to dominate that part, and that’s where you find the value of precision medicine.”
A diagnostic test for obesity is only as effective as the number of treatments available for each result. But Bagnall said the drug pipeline is deep and diverse with the potential to fill treatment gaps that have been difficult to understand from person to person.
A personalized approach is also important for overcoming the stigma surrounding obesity.
“One of the things that is so difficult if you’re a patient is that you’ve been told obesity is a moral failing, that it’s your fault — and now you have a test that comes back and says you have a very specific type of obesity that has a genetic component to it,” Bagnall said. “Now we know the intervention that’s right for you and we’re going to treat it like a disease.”
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