“Hungry gut” vs. “hungry brain”: Test could help decide who gets obesity drugs

• Homing in on obesity's genetic underpinnings through precision medicine may represent a more cost-effective way of tackling weight loss, Phenomix Sciences says.

What they're saying: "We're not going to solve the obesity crisis by treating 100 million people" with drugs like Wegovy, which has a list price of $16,000 a year, Phenomix CEO Mark Bagnall told Axios.

• "That feels like not a wise choice and there are other interventions available," said Bagnall.

Details: The company was founded by Mayo physician-researchers Andres Acosta and Michael Camilleri in 2017, with backing from the American Medical Association's innovation arm, Health2047.

• The company's central thesis — detailed in the journal Obesity in 2021, around the time GLP-1s were starting to take off — states there are at least four different biological mechanisms underlying obesity, and each responds differently to treatment.
• Its research finds about 60% of those struggling with obesity fall into two categories: "Hungry gut" patients, who tend to snack between meals because food moves quickly through their digestive tract, and "hungry brain" patients, who tend to need additional calories to feel full, said Bagnall.
• The company sells to doctors genomic tests that use AI-based algorithms to determine if a patient is in one of those two categories.
• There are also "emotional eaters" who eat for an emotional reward and "slow burn" patients who may have a slow metabolism, Bagnall said. The company is still researching what treatment approach may be helpful for those patients.

Zoom in: Those with "hungry gut" are mostly likely to benefit from GLP-1s, which slows gastric emptying, according to Phenomix research that dates back to 2017.

• On the other hand, those with "hungry brain" are more successful on an older, cheaper drug called Qsymia that acts as an appetite suppressant.
• Patients wanting to figure out if they fall in either category have the test ordered by their doctor, fill out a questionnaire about their general health history and complete a saliva test. Results are returned in four to six weeks.
• "In our studies, if we find someone who is hungry brain-positive and put them on Qsymia, we get better [results]. And while Wegovy is $1,259 a month, you can get with a coupon Qysmia for $100 and it doesn't have those ugly side effects," Bagnall said. "That's the value prop."
• The tests retail at about $500 and aren't covered by insurance, so patients pick up the entire cost.

• "It really goes to show you how much patients are kind of tired of guessing at things," said Phenomix chief operating officer Liv Williamsen. "They'd rather spend some money upfront to figure out what the solution is, as opposed to being in the same place in two years."

The big picture: Other researchers are searching for biomarkers to better target GLP-1 use.

• For example, a study of Type 2 diabetics in The Lancet Diabetes & Endocrinology last year found Hispanic and American Indian or Alaska Native populations are more likely to have a genetic variant indicating they may respond particularly well to GLP-1s agonists compared with European white populations.

There's also a growing industry of companies trying to use GLP-1s in a more effective way.

• Companies like Lark Health and Calibrate are studying how to effectively wean patients off the drugs to different anti-obesity medications or lower doses of GLP-1s.
• Virta Health focuses on fighting "carbohydrate intolerance," offering low-carb food-as-medicine plans with the goal of reducing GLP-1 prescriptions.

What's next: Phenomix is talking with multiple drug companies who are interested in potentially incorporating the tests into their development programs to better target their drug candidates, Williamsen said.

• Health plans and employers are also considering covering the tests, Bagnall said.
• One company that self-funds its health plan told him it's seen a 25x jump in obesity drug costs in three years.
• "They're faced with this phenomenal increase in costs," Bagnall said. "We're either going to be spending money on obesity drugs and nothing else, or we have to fix it because if it keeps going up at that rate, we're done."