New data suggest Vivani’s miniature exenatide implant, NPM-115, works as well as Novo Nordisk’s Wegovy and Ozempic for weight loss in mice. The implant delivers high doses of exenatide, a GLP-1 receptor agonist commercialized by AstraZeneca as Bydureon for treating Type 2 diabetes.
The data, posted by the company Feb. 28, offer new evidence that exenatide is effective for weight loss in non-diabetic animals. They also justify Vivani’s recent shift from focusing on Type 2 diabetes to weight loss, Vivani CEO Adam Mendelsohn, Ph.D., said in a press release.
“In response to tremendous medical need and unprecedented market demand, we are prioritizing the development of our GLP-1 implants for the treatment of obesity and chronic weight management,” Mendelsohn said. “Since a high-dose GLP-1 implant for obesity would likely also be able to address our previous type 2 diabetes focus, the recently generated compelling weight loss data from NPM-115 naturally supports a shift in focus towards an indication with even broader potential.”
In the new study, seven mice with obesity caused by a high-fat diet lost nearly 20% of their body weight within 28 days of being implanted with NPM-115, the same amount lost by obese mice that were injected with high doses of semaglutide—the active ingredient in Ozempic and Wegovy—over the same period. The implant delivered daily doses of exenatide at around 530 nmol/kg/day, while the mice on semaglutide received doses of around 2,700 nmol/kg/week. These higher-than-typical doses were given to “maximize the weight loss potential of both exenatide and semaglutide,” according to Vivani.
A second study on an exenatide implant Vivani is developing for Type 2 diabetes, NPM-119, also stimulated significant weight loss in healthy rats. The animals’ body weight was 25% lower at 15 weeks post-implantation than rats with an implant that delivered a control solution. In this case, exenatide was delivered at a lower dose of around 320 nmol/kg/day. Given that NPM-119 secretes smaller amounts of exenatide than NPM-115, Vivani expects that NPM-115 will prove equally durable for weight loss.
Vivani’s core technology is its NanoPortal device, a tiny titanium cylinder with a reservoir for medication. Drugs are released through nanotubes with pores that are sized according to how quickly or slowly the medication should be delivered. The device is placed under the skin, where it secretes drugs for six months before being replaced. Vivani is working on another implant, NPM-139, that secretes semaglutide for up to a year.
Drug-secreting implants are an attractive prospect for dosing GLP-1 therapies for weight loss, as less-frequent dosing has been shown to improve adherence. They could also potentially enable exenatide to join the roster of weight management meds, as potential limitations around dosing and adherence have kept it from being considered for that indication so far, Vivani said.
If Vivani were to succeed at getting its implants through the FDA, it would be the first. Intarcia Therapeutics, once a biotech unicorn, faced FDA rejection of its six-month diabetes drug implant for the third time in September 2023 due to potential safety issues. Those concerns were centered on dosing stability, as large, uncontrolled boluses of GLP-1 receptor agonists could lead to complications, like GI issues, kidney failure and heart problems.
Vivani's implant is different because it has "a non-viscous formulation and no moving piston, and is associated with smooth and steady release profiles," Mendelson told FBR in an email. While the current study didn't go on for long enough to measure outcomes like the ones the FDA was concerned about in the mice, "it is reasonable that a minimally-fluctuating release profile could avoid this cascade of events," he said.
Editor's note: This article has been updated from its original version to add a comment from Mendelson on how Vivani's technology differs from Intarcia's.