RESOLVING THE LEDGER
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Scientists might be inching closer to a breakthrough that some of us lazy bums would very much appreciate: a pill that can safely provide the same healthy benefits of exercise.
On Tuesday, the pharmaceutical company Enveda announced the results of a Phase I trial of its experimental drug ENV-308, which is designed to mimic a hormone released while exercising. In healthy volunteers, the trial showed that ENV-308 appears to be safe and well-tolerated, and Enveda is hoping that the drug can help people maintain their weight loss and hold onto their muscle mass, all without causing the well-known gastrointestinal side effects seen with popular GLP-1 drugs like semaglutide.
"ENV-308 is our attempt to put the chemistry of exercise into a daily tablet, and to offer a sustainable and convenient solution that synergizes with people’s daily habits and supports them on the path to long-term health,” said Viswa Colluru, founder and CEO of Enveda, in a company statement .
ENV-308 mimics a recently discovered molecule called N-lactoyl-phenylalanine, or Lac-Phe for short. Our bodies seem to produce Lac-Phe in higher amounts during intense exercise as well as after eating. Studies have indicated that it helps suppress appetite, and obese mice treated with Lac-Phe have been shown to lose weight as a result. That's made scientists curious about its potential as an obesity drug.
Naturally occurring Lac-Phe only lasts for a short time in the body, however. ENV-308 is intended to stick around long enough to be taken as a once-a-day pill. According to the company, it was discovered via Enveda's proprietary AI model PRISM .
In this first human trial of ENV-308, 88 healthy adults were given varying doses of the drug. Phase I trials are mainly intended to gauge the safety of an experimental drug or vaccine, and ENV-308 seemed to pass this initial test with flying colors. No serious adverse events were reported among the volunteers, nor did anyone stop taking the drug. Notably, it also had an "exceptional gastrointestinal safety profile," the company stated.
The trial may have additionally shown some early signs of Lac-Phe working as hoped. People with obesity are known to often have elevated levels of leptin, a hormone that helps signal fullness while eating. It is hypothesized that this is because people's bodies stop responding to leptin as well as they should.
In studies of obese animals, ENV-308 has rapidly lowered leptin levels, suggesting it can reverse this dysfunctional response. During the trial, researchers found lower circulating levels of leptin in the human volunteers, as well.
This research is in its early days, and should the company's development of ENV-308 continue to prove successful, it can't fully replace the need for exercise. Even assuming Lac-Phe is as helpful as we think it might be, it's only one of many positive changes that exercise produces.
Still, finding new ways to treat obesity or other metabolic conditions remains important. Some people are unable to tolerate the GI side effects common to GLP-1s, while others might prefer the convenience of a daily pill over a weekly injection (though some GLP-1s are also now available as a pill). Muscle loss isn't a major concern for most GLP-1 users, but some people are more vulnerable to it, like older adults, and they could benefit from an obesity treatment that can better preserve muscle.
Enveda plans to continue testing ENV-308 in a larger Phase II trial for weight loss maintenance, and it's evaluating the drug for other conditions that might benefit from its exercise-like effects, such as migraines and inflammatory bowel disease.
Ideally, ENV-308 will show that it is possible to safely mimic or even amplify at least some of the best aspects of exercise. I'm not giving up my running routine anytime soon, mind you, but I'll definitely be hoping that ENV-308 is only the first of many drugs that can do so.
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