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December 5, 2022

Amgen brings the latest candidate to a new generation of weight loss drugs

Daily Briefing

    On the heels of several new, buzzy weightless drugs, Amgen is the latest to release "promising" results from a Phase 1 trial of its new weight loss drug—but some experts warn that the high-dose drug could have "higher side effects that are maybe not tolerable."

    A new generation of weight loss drugs

    New weight loss drugs, which are repurposed diabetes medications, "are showing weight loss unlike any other medications we've had in the past," according to David Creel, a psychologist and registered dietitian in the Bariatric & Metabolic Institute at the Cleveland Clinic.

    For instance, Novo Nordisk's Wegovy, or semaglutide, is a higher dose of the company's self-injectable diabetes drug Ozempic. It mimics a hormone called glucagon-like peptide-1 (GLP-1) to target areas of the brain that regulate appetite and food intake.

    Wegovy received FDA approval last year after a clinical trial showed it helped patients lose an average of 15% of their body weight over 68 weeks. Robert Kushner, an obesity researcher at Northwestern University Feinberg School of Medicine who led the clinical trial for Wegovy, called it a "game-changer" and the "start of a new era of effective treatments for obesity."

    Similarly, Eli Lilly in June reported promising results for its experimental obesity drug tirzepatide. During the trial, patients lost up to 20% of their body weight. Currently, it has only been approved by FDA to treat Type 2 diabetes under the name Mounjaro, but it will likely soon be approved for weight loss as well.

    Amgen releases early-stage weight loss drug data

    On Thursday, Amgen released data on its early-stage weight loss drug, known as AMG 133. While AMG 133 produced results similar to semaglutide and tirzepatide, the drug is slightly different. With AMG 133, an antibody blocks glucose-dependent insulinotropic peptide (GIP) while two peptides mirror the actions of GLP-1, which may help boost weight loss and keep the drug in the body longer, according to Amgen.

    After 12 weeks, the eight trial patients who received the high dose of AMG 133 experienced an average weight loss of 14.5%. While still early, experts said the trial data was notable.

    A "14.5% total body weight loss certainly looks promising!" said Katherine Saunders, an obesity specialist at Weill Cornell Medicine and founder of the obesity-focused telehealth company Intellihealth. "Monthly dosage would be very attractive for individuals who aren't thrilled about injecting," she added.

    Separately, Narimon Honarpour, Amgen's VP of global development, noted that patients' weights were still dropping at 12 weeks. "We didn't see any evidence of a plateau of effect" he said, noting that rival drugs saw a similar benefit over time.

    However, Kushner noted that one part of the drug's strategy was confusing. The drug activates GLP-1 satiety receptors, while blocking the GIP hormonal receptor. According to Honarpour, studies suggest that patients with low GIP typically have lower body weight.

    "It's hitting the brakes on one pathway, while it's stepping on the accelerator for the other," Honarpour said.

    Amgen's new drug may have side effects that are 'not tolerable'

    According to Amgen, AMG 133 will likely have similar side effects to other newer weight loss drugs. Both semaglutide and tirzepatide can trigger gastrointestinal problems, including diarrhea, vomiting, or nausea. In Amgen's Phase 1 trial, which included several different arms and doses, all 20 patients who received multiple doses of the drug reported some kind of mild GI stress.

    While the weight loss data is "certainly competitive," Kushner noted that it could appear less impressive if the company lowers the dose to make the drug more tolerable.

    "What's not here is the side effect profile," Kushner said. "Higher doses are often associated with higher side effects that are maybe not tolerable."

    However, Saunders said she believed the side effects were "not unexpected" due to the class of drugs and "can generally be mitigated or avoided" with dosing strategies.

    Amgen intends to start a larger Phase 2 study next year to test a variety of dosing strategies and understand the drug's efficacy over the course of a full year. (Jarvis, Bloomberg/Washington Post, 12/4; Mast, STAT+, 12/1 [subscription required])

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