Amgen claims to have made weight loss history by producing the first proof of a reduction in body weight for a monthly obesity treatment in a phase 2 study—but it isn’t enough to enthuse investors.
Unlike Eli Lilly's Zepbound, which is a dual agonist of the GLP-1 and GIP receptors, Amgen's MariTide is a monoclonal antibody linked to a pair of peptides that increase GLP-1 receptor activity while tamping down on the receptor for GIP. Today's readout linked MariTide to an average weight loss of up to 20% over 52 weeks in individuals living with obesity or overweight but without type 2 diabetes. For those with diabetes, the average weight loss reached 17%.
The trial enrolled 592 adults in total across the diabetes and non-diabetes cohorts, who received either a monthly MariTide dose of 140 mg, 280 mg or 420 mg, an eight-week 420-mg dose, or placebo. A weight loss plateau was not observed for either cohort, which Amgen said “indicat[es] the potential for further weight loss beyond 52 weeks.”
The 20% weight loss figure highlighted by Amgen was reached by the 280-mg monthly patient group, according to the company’s presentation, with the pooled two 420-mg dosing regimens and the 140-mg monthly dose groups following slightly behind.
While trial-to-trial comparisons are difficult, Novo Nordisk’s GLP-1 blockbuster Wegovy achieved 14.9% average weight reduction in STEP-1, a 68-week clinical trial of nondiabetic patients with obesity or who are overweight and have at least one weight-related comorbidity. Meanwhile, Lilly’s Zepound achieved 21.1% mean weight loss over 36 weeks.
Unlike those two weekly options, MariTide can be dosed once a month or less. Metsera and Terns Pharmaceuticals, to name a few, have monthly obesity prospects in the clinic, but have yet to reach a phase 2 readout. Novo Nordisk had been working on a once-monthly GLP-1/GIP receptor agonist, but axed the program in August due to an unimpressive clinical profile seen in phase 1 testing.
“There's a lot to love about monthly or less frequent dosing,” Jay Bradner, M.D., Amgen’s EVP of R&D and Chief Scientific Officer, told analysts on a call to discuss today's data. He pointed to using “fewer devices” and “less peptide” than weekly options.
Today’s results fell just within the expectations of BMO Capital Markets, which last week was expecting to see placebo-adjusted weight loss somewhere in the 19%-22% range.
But Leerink analysts reflected this morning that the findings were “roughly on par” with Zepbound (tirzepatide), meaning that MariTide’s “only differentiation appears to be dosing frequency.”
The analysts also flagged that MariTide showed “no significant increases in free fatty acids … whereas free fatty acids decreased by 7.5% with pooled groups of tirzepatide in the phase 3 SURMOUNT-1 trial.”
Investors also seemed unimpressed, initially sending Amgen’s shares down 10% to $262.88 when the markets opened on Tuesday morning.
Bradner insisted to analysts on this morning’s call that Amgen sees “a quite differentiated profile, really across all terms of efficacy, tolerability, dosing and patient experience” when it comes to MariTide.
In response to a question from analysts, Bradner said Amgen could “potentially” run a head-to-head trial of MariTide with approved weight loss drugs, but he didn’t offer any concrete plans.
In the Nov. 26 release, Amgen also highlighted that MariTide “demonstrated robust and clinically meaningful improvements in cardiometabolic parameters, including blood pressure, triglycerides and high-sensitivity C-reactive protein across doses.”
The most common side effects were nausea and vomiting, which the company said were “predominately mild, transient and primarily associated with the first dose.”
The discontinuation rate in the dose escalation arms due to any adverse event was around 11% and under 8% for gastrointestinal-related events specifically. No additional safety signals were identified, Amgen added.
“We are already seeing less than 20% vomiting without a requirement for use of concomitant antiemetic medication,” Bradner said. “And so through design, decreased ascertainment bias, perhaps coaching and other best practices, we hope to see even better data as we progress from phase 2 to phase 3.”
MariTide made headlines for the wrong reasons earlier this month when an accidentally disclosed tab on a spreadsheet of phase 1 data raised concerns that the drug could be linked to a reduction in bone density. On this morning’s call, Bradner made sure to “specifically highlight that there were no changes in bone mineral density observed.”
Looking ahead, the pharma said it will continue to evaluate patients in the phase 2 trial to assess any further weight loss, and is now gearing up for a phase 3 obesity trial.
“We are very excited by MariTide's differentiated profile, with clinically meaningful attributes of substantial and progressive weight loss, monthly or less frequent dosing, significant improvements in cardiometabolic parameters and strong reduction of HbA1C,” Bradner said in a statement.
“These results provide us confidence to initiate MARITIME, a phase 3 program across obesity and a number of related conditions, providing a unique potential new treatment option for patients.”