Amgen announced positive results from a Phase II clinical trial evaluating its investigational obesity drug MariTide (maridebart cafraglutide, formerly AMG 133) for the treatment of obesity and overweight in both diabetic and non-diabetic patients.
Among the next generation of obesity drugs, MariTide is a top GLP-1 contender that touts the potential for enhanced efficacy and more convenient, less frequent dosing.
Unlike the reigning blockbuster GLP-1 drugs on the market — namely Novo Nordisk’s Wegovy (semaglutide) and Eli Lilly’s Zepbound (tirzepatide), the latter of which is a dual agonist of the GLP-1 and GIP receptors — Amgen’s MariTide is an antibody-peptide conjugate that combines a GLP-1 receptor agonist (consisting of two peptides that mimic the GLP-1 hormone) and GIP receptor antagonist (an antibody that blocks the receptor).
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Amgen’s randomized, double-blind, placebo-controlled Phase II study enrolled 592 adults with obesity or overweight conditions, defined by a body mass index (BMI) of ≥30 or ≥27, respectively, with at least one obesity-related comorbidity.
The trial included 465 participants who were either obese or overweight. They were randomly assigned to receive a placebo, one of four fixed monthly doses of MariTide (placebo, 140 mg, 280 mg or 420 mg), a single fixed dose of 420 mg for eight weeks, or one of two dose-escalation regimens up to the maximum dose.
Additionally, 127 participants who were obese or overweight and also had type 2 diabetes were enrolled. These individuals were randomized to either the placebo group or one of the monthly fixed-dose groups (placebo, 140 mg, 280 mg or 420 mg).
Amgen’s Phase II study showed that MariTide led to a weight loss of 20 percent in participants with obesity or overweight without type 2 diabetes after 52 weeks of treatment. The weight loss was sustained and did not hit a plateau.
In people with obesity or overweight and with type 2 diabetes, MariTide demonstrated up to an approximately 17 percent average weight loss at 52 weeks, also without evidence of a weight loss plateau, which Amgen said indicates scope for further weight loss beyond 52 weeks. Additionally, the therapy significantly lowered average HbA1c levels by up to 2.2 percentage points, highlighting its dual benefit for weight and glycemic control.
The ongoing second part of the study is evaluating MariTide beyond 52 weeks, looking at additional weight loss with continued treatment, weight maintenance using less frequent or lower dosing and durability of weight loss following treatment discontinuation. According to Amgen, more than 90 percent of eligible patients chose to continue to participate in Part 2 of the study.
In a company presentation, Amgen shared that the 20 percent weight loss data point was reached in the 280-mg monthly patient group, with the pooled two 420-mg dosing regimens and the 140-mg monthly dose groups just slightly behind.
Participants receiving the highest dose of MariTide experienced an average weight loss of 21.6 percent of their baseline body weight at the end of 52 weeks, compared to a 2.4 percent weight reduction in the placebo group.
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According to Amgen, MariTide is designed for administration via a single dose using a convenient, handheld, patient-friendly autoinjector device.
The therapy is expected to require monthly or less frequent single-injection dosing, making it the first obesity treatment with a longer dosing schedule shown to induce safe and effective weight loss in a Phase II study.
“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,” said Jay Bradner, MD, executive vice president of Research and Development and chief scientific officer at Amgen in a press release announcing the trial data.
“These results provide us confidence to initiate MARITIME, a Phase III program across obesity and a number of related conditions, providing a unique potential new treatment option for patients.”
MariTide was well-tolerated across all dosage groups, with the most common side effects being mild gastrointestinal symptoms, such as nausea and diarrhea, which were largely “mild, transient and primarily associated with the first dose,” according to Amgen.
The discontinuation rate in the dose escalation arms due to any adverse event was around 11 percent and under eight percent for gastrointestinal-related events specifically. Amgen said no additional safety signals were identified.
Amgen said the Phase II data will be presented at an upcoming medical congress and will also be submitted for publication.
The study also reported significant improvements in obesity-related comorbidities, including better glycemic control, reduced blood pressure and improved lipid profiles among those treated with MariTide.
However, analysts at Leerink were critical of the latter, saying that there were “no significant increases in free fatty acids … whereas free fatty acids decreased by 7.5 percent with pooled groups of tirzepatide in the Phase III SURMOUNT-1 trial.”
The analysts were referring to trial data for Eli Lilly’s Zepbound, which demonstrated a mean weight loss of 21.1 percent over 36 weeks in its trials involving nondiabetic patients with obesity or overweight, making MariTide’s results “roughly on par” with Zepbound, despite the difficulty of cross-trial comparisons. Given this, the analysts pointed out that MariTide’s “only differentiation appears to be dosing frequency.”
Novo Nordisk’s GLP-1 weight loss blockbuster Wegovy led to an average weight reduction of 14.9 percent in the 68-week STEP-1 clinical trial.
“There’s a lot to love about monthly or less frequent dosing,” Bradner, on a call with analysts, expressing optimism about “fewer devices” and “less peptide” than weekly options.
Bradner also said Amgen could run a head-to-head trial of MariTide with approved weight loss drugs in response to a question from the analysts, but didn’t specify any plans for it.
Nevertheless, the analysts’ comments seemingly had an impact on investors as Amgen’s shares dropped as much as 12 percent to $262.88 on Tuesday morning, the company’s steepest fall in 23 years, according to Bloomberg.
Obesity affects over 650 million adults worldwide and is a major risk factor for chronic conditions such as type 2 diabetes, cardiovascular disease and certain cancers. Current treatment options are limited by efficacy, tolerability and accessibility.
Amgen plans to initiate global Phase III clinical trials in early 2025 to further evaluate MariTide’s efficacy and safety in a larger and more diverse population. The company is also exploring MariTide’s potential for treating additional conditions, such as non-alcoholic steatohepatitis (NASH), now known as metabolic dysfunction-associated steatohepatitis (MASH) and type 2 diabetes.
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