Amgen is trying a unique strategy with its obesity drug candidate: testing whether it can wean patients toward lower or less frequent doses over time.
Very early data hints that Amgen’s candidate, called MariTide, may provide longer-lasting weight loss than highly popular obesity drugs on the market like Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound. Amgen is already seeing if that means its drug could also be dosed differently from Novo and Lilly’s products, which are costly and expected to be taken consistently for life.
In an ongoing Phase 2 trial, Amgen’s researchers will first titrate participants up on MariTide, but then after some time, see if the drug can still be effective when transitioning patients to a less intensive dosing regimen, executives said in an interview.
“Could there be an opportunity for an induction maintenance-type of strategy for a molecule like MariTide?” said Narimon Honarpour, senior vice president of global development at Amgen, referring to a strategy used for anti-inflammatory drugs in which high, rapid doses are given at the start and then lower or less frequent doses are used for maintenance in the long run.
It’s unclear if patients would be able to completely come off MariTide. Honarpour said they anticipate patients would need to keep taking some amount of the treatment to continue to get benefits, but “we do want to be students of the data” and they will see what happens in the trial when patients completely stop taking the drug.
Amgen’s treatment, a monoclonal antibody, already stands out in that it’s designed to be taken monthly, whereas Wegovy and Zepbound are taken weekly. If the ongoing trial shows that it can be taken even less frequently for maintenance while still delivering weight loss, then it could be an especially competitive product in a market that dozens of drugmakers are trying to jump into.
Already, some patients on Wegovy or Zepbound have been trying to stay on lower doses or take less frequent doses for weight loss maintenance, said Angela Fitch, chief medical officer at knownwell, a health provider that treats people with obesity.
Novo and Lilly are also researching new candidates that could deliver long-lasting weight loss. Novo in particular is looking at potential RNA-interference treatments for obesity, it previously told STAT.
Wegovy and Zepbound are the first approved drugs in a new class of obesity treatments that has drawn immense demand for causing unprecedented levels of weight loss. Wegovy works by activating receptors of the GLP-1 hormone, while Zepbound targets receptors of both the GLP-1 and GIP hormones.
Amgen’s drug is different in that it activates GLP-1 receptors while blocking receptors of the GIP hormone. Even though this mechanism appears contradictory to that of Zepbound’s, Amgen’s candidate proved effective in an early phase 1 study.
In that trial, the eight patients who received the highest dose lost on average 14.5% of their weight over about three months. (Meanwhile, Wegovy and Zepbound showed 15-21% weight loss in trials lasting over a year.)
And the weight loss lasted even after patients’ last dose, according to detailed data from this study, published Monday in Nature Metabolism. Participants maintained maximum weight loss until two months after their last dose, and while their weight started to slowly creep back up after that, their body weight was still 11% lower at five months after the last dose.
Though this trial was small, the results contrast with what’s seen in trials of Wegovy and Zepbound, in which people’s weight started rebounding much sooner after stopping the drugs.
MariTide is a monoclonal antibody, a type of drug that lasts in the body longer than other types of medications. But what’s intriguing is that people seem to still maintain their weight loss even when the drug is no longer circulating in the body, said Randy Seeley, director of the Michigan Nutrition Obesity Research Center.
“The most interesting thing that is in that data is the hint that when you take the molecule away, you do not get the level of weight rebound that you would expect,” he said. Seeley will be conducting research funded by Amgen to study MariTide. He also consults for other companies like Novo and Lilly.
A consideration for MariTide is that since it’s a monoclonal antibody, which consists of larger molecules than other drugs, it likely doesn’t cross the blood-brain barrier, a membrane that surrounds the brain. Some researchers think that part of the reason Wegovy and Zepbound are so effective is that they do get past the barrier and act in the brain to help reduce food cravings and provide other benefits like lower inflammation.
Still, Seeley thinks it makes sense for drug developers to prioritize developing longer-lasting therapies in the obesity space.
“For me, the most important thing that we could do is to get closer to one and done versions of this,” he said. “The notion that we could build pharmaceutical interventions that would have long lasting effects beyond the status of the drug is incredibly intriguing.”
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