Key takeaways:
- Maridebart cafraglutide is a twin GLP-1/GIP being investigated for the therapy of weight problems and diabetes.
- As soon as-monthly dosing led to important weight reduction in adults with weight problems, with or with out diabetes.
CHICAGO — As soon as-monthly maridebart cafraglutide resulted to important weight reduction at 1 12 months amongst adults with weight problems, no matter kind 2 diabetes standing, in accordance with information from a part 2 trial.
Healio beforehand reported information from the part 2 trial through which maridebart cafraglutide (MariTide, Amgen), administered once-monthly through subcutaneous injection, was tied to larger reductions in physique weight, systolic blood stress, LDL ldl cholesterol, triglycerides and high-sensitivity C-reactive protein in contrast with placebo. Closing information from the part 2 trial have been introduced on the American Diabetes Affiliation Scientific Classes and concurrently revealed in The New England Journal of Medication.
As soon as-monthly maridebart cafraglutide conferred weight lack of as much as 16.2% within the therapy coverage estimand amongst adults with weight problems and with out diabetes. Picture: Adobe Inventory
MariTide is a bispecific GLP-1 receptor agonist and glucose-dependent insulinotropic polypeptide (GIP) receptor antagonist. Its twin mechanism of motion and longer half-life assist month-to-month or much less frequent administration, in accordance with the researchers.
Ania M. Jastreboff
“To have one thing that’s once-monthly or much less frequent that each addresses their dysglycemia in addition to handle the basis reason behind their diabetes, which is weight problems, is exclusive,” Ania M. Jastreboff, MD, PhD, affiliate professor of drugs and pediatrics (endocrinology) at Yale College College of Medication, director of the Yale Weight problems Analysis Middle, co-director of the Yale Middle for Weight Administration and medical director of the Yale Stress Middle, mentioned throughout a press convention.
Researchers enrolled 592 adults with weight problems or obese plus one obesity-related complication within the double-blind randomized managed trial. Two cohorts have been assessed: adults with weight problems with and with out diabetes. Contributors with weight problems and with out diabetes have been randomly assigned to obtain 140 mg, 280 mg or 420 mg of maridebart cafraglutide each 4 weeks with out dose escalation; 420 mg each 8 weeks with out dose escalation; 420 mg each 4 weeks with a 4-week dose escalation; 420 mg each 4 weeks with a 12-week dose escalation; or placebo. Contributors with weight problems and sort 2 diabetes have been randomly assigned to 140 mg, 280 mg or 420 mg of maridebart cafraglutide each 4 weeks or placebo. Change in physique weight from baseline to 1 12 months was the first endpoint.
Outcomes: Weight problems with out diabetes
The trial included 465 adults with weight problems however with out diabetes (imply age, 47.9 years; 63% ladies; imply BMI, 37.9 kg/m2).
At 1 12 months, imply % change in physique weight from baseline ranged from –12.3% to 16.2% within the MariTide group, in contrast with –2.5% for these assigned placebo within the therapy coverage estimand (intention-to-treat method), in accordance with the outcomes.
Within the efficacy estimand, which the researchers mentioned represents the efficacy as if handled members had adhered to MariTide for your complete examine interval, imply % change in physique weight at 1 12 months was even larger, and ranged from –16.3% to –19.9%, in contrast with –2.6% with placebo. Throughout a presentation, Julio Rosenstock, MD, FACE, senior scientific advisor for Velocity Medical Analysis, director of Velocity’s web site at Medical Metropolis Dallas and medical professor of drugs on the College of Texas Southwestern Medical Middle, mentioned the distinction between the therapy coverage estimand and efficacy estimand have been larger than what has been seen in different weight problems trials and added the distinction could also be because of the examine’s discontinuation charge. Of the members with weight problems and with out diabetes assigned MariTide, 16.8% discontinued the therapy as a result of an opposed occasion.
Adults with weight problems and with out diabetes additionally had a lower in fats mass starting from –26.2% to –36.8% with maridebart cafraglutide at 1 12 months in contrast with –9.1% with placebo. Lean mass was diminished by –8.6% to –11.6% vs. –2.1%, respectively.
Jastreboff mentioned weight reduction in all teams had not but plateaued at 1 12 months.
“We don’t know the complete efficacy of this agent till we glance farther out,” Jastreboff mentioned.
Outcomes: Weight problems with kind 2 diabetes
The trial included 127 adults with weight problems and sort 2 diabetes included within the trial (imply age, 55.1 years; 42% ladies; imply BMI, 36.5 kg/m2).
At 1 12 months, MariTide conferred larger weight reduction amongst adults with weight problems plus than placebo. The imply % change in physique weight in accordance with the therapy coverage estimand ranged from –8.4% to –12.3%, in contrast with –1.7% within the placebo group, in accordance with the outcomes. Within the efficacy estimand, weight reduction with maridebart cafraglutide ranged from –12.1% to –17%, in contrast with –1.4% within the placebo group, in accordance with the outcomes.
Jastreboff mentioned the magnitude of weight reduction within the kind 2 diabetes group, significantly these assigned 420 mg MariTide, was spectacular.
“People with kind 2 diabetes often lose much less weight than these with weight problems [alone],” Jastreboff mentioned. “This was an excellent consequence to see.”
HbA1c additionally decreased amongst adults with weight problems and diabetes assigned MariTide. Within the efficacy estimand, declines in HbA1c ranged from –1.9 to –2.2 share factors, in contrast with a 0.1 share level enhance within the placebo group, in accordance with the outcomes.
Fats mass decreased between –17.4% and –33.7% at 1 12 months within the MariTide group, whereas lean mass was diminished by –6.8% to –9.6%. The placebo group had a 4.3% lower in fats mass and a couple of.3% decline in lean mass.
Security information
No less than 90% of members assigned MariTide in each cohorts reported at the very least one opposed occasion, in contrast with 68% of the placebo group with weight problems and with out diabetes and 81% of these with weight problems plus kind 2 diabetes assigned placebo. Gastrointestinal opposed occasions have been the commonest amongst adults assigned MariTide. Most GI occasions have been delicate to average and have been extra more likely to happen amongst members who didn’t obtain dose escalation of MariTide, in accordance with the researchers. GI occasions have been the commonest purpose for therapy discontinuation.
“The efficacy and security of part 2 assist the investigation of MariTide in part 3,” Jastreboff mentioned throughout a presentation.
Enhancing gastrointestinal tolerability
Researchers additionally reported outcomes of a part 1, pharmacokinetics low-dose initiation examine, which evaluated decrease beginning doses, knowledgeable by the pharmacokinetics of MariTide.
This included 121 adults who have been randomly assigned to a beginning dose of 21 mg, 35 mg or 70 mg of MariTide. All three teams had a rise to 70 mg at day 15 and to 350 mg at day 29. Monitored occurred in an inpatient setting the primary 7 days after receiving a dose. The first evaluation for this examine was carried out at 43 days.
Imply plasma concentrations of MariTide have been greater through the first 15 days within the higher-dose teams. Imply ranges of publicity to the MariTide elevated at day 15 and day 29, with a bigger enhance within the lower-dose teams than the 70 mg beginning dose cohort. Donna H. Ryan, MD, professor emerita at Pennington Biomedical Analysis heart, who introduced the outcomes, mentioned plasma concentrations of the drug at day 29 have been related between the three teams.
At day 43, GI opposed occasions occurred in 61% of the 21 mg dose group, 77.5% of the 35 mg group and 92.5% of the 70 mg group.
Donna H. Ryan
Contributors accomplished a Modified Index of Nausea, Vomiting and Retching every day of the examine. Through the first 15 days, the 21 mg group had the bottom prevalence of GI opposed occasions. Nevertheless, after day 15, when all teams elevated their dose to 70 mg, GI occasions have been related within the 21 mg beginning dose group in contrast with 30 mg and 75 mg beginning doses.
“We predict what is going on on is, after we look again at our pharmacokinetics examine, we see that giant plasma enhance,” Ryan mentioned. “We predict that’s in all probability driving the elevated occasions on day 15. This might recommend that an intermediate dose would alleviate a few of these issues.”
Based mostly on the pharmacokinetic findings, Ryan mentioned the researchers have a plan for dose escalation in a future part 3 examine. Ryan mentioned members assigned MariTideg will begin at 21 mg at baseline, enhance to 35 mg at 2 weeks after which enhance once more to 70 mg at 4 weeks. At 8 weeks, members shall be randomly assigned to one in every of three goal doses.
“We predict it is a nice alternative right here and we’re actually enthusiastic about that lengthy half-life and the potential for month-to-month and even much less frequent dosing,” Ryan mentioned.
Reference:
Sources/Disclosures
Collapse
Seeley RJ, et al. As soon as-monthly MariTide for the therapy of weight problems in folks with or with out kind 2 diabetes — A 52-week part 2 examine. Offered at: American Diabetes Affiliation Scientific Classes; June 20-23, 2025; Chicago.
Disclosures:
Jastreboff experiences receiving grant funding from Amgen, Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Rhythm Prescribed drugs; consulting for Amgen, AstraZeneca, Biohaven Pharmaceutical, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Pfizer, Regeneron, Scholar Rock, Construction Therapeutics, Terns, WW and Zealand; and proudly owning inventory choices in Intellihealth, State 4 Therapeutics and Syntis Bio. Ryan experiences serving as a scientific advisor for AbbVie, Altimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Biohaven, Calibrate, Carmot/Roche, CINRx, Currax, Eli Lilly, eMedd, Epitomee, Fractyl, Gila, Nestle, Novo Nordisk, Pfizer, Regeneron, Scientific Consumption, Supply Bio, Construction Therapeutics, Tenvie, Wondr Well being and Zealand; serving on a speaker’s bureau for Eli Lilly and Novo Nordisk; proudly owning inventory choices in Calibrate, Epitomee, Roman, Scientific Consumption and Xeno Bioscience; and serving on an information security monitoring board for CINRx, Eli Lilly and IQVIA setmelanotide.
