While Amgen’s monthly obesity candidate MariTide helped patients lose significant amounts of weight in a phase 2 study, prevalent gastrointestinal side effects are leading the company to use a slower dosing schedule in its late-stage trials.
Amgen presented the results of part 1 of its phase 2 MariTide study at the American Diabetes Association's (ADA's) 85th Scientific Sessions in Chicago on Monday, and the data were simultaneously published in The New England Journal of Medicine (NEJM). The study tested the candidate, a GLP-1 agonist and GIPR antagonist, in patients with obesity as well as those with both Type 2 diabetes and obesity.
The drug was shown to prompt weight loss across the board, with those with obesity losing an average of 16.2% of their baseline body weight and those with diabetes and obesity shedding 12.3% of their weight on average. However, when looking at only patients who stayed on treatment over the entire 52-week study period, the results came out to average weight loss of 19.9% and 17% between the two patient groups, respectively.
By Week 52, patients' weight loss had not yet plateaued, indicating the drug's potential to trigger further weight loss after one year, Amgen noted in its press release.
Early discontinuation due to adverse events occurred with varying frequency across the treatment cohorts, but the trend was most notable in those who took higher doses without going through a dose-escalation process first. Of those with obesity who took different doses of the drug without dose escalation, 12% to 27% stopped their trial regimen early due to gastrointestinal events. In the dose-escalation groups, the discontinuation rates due to gastrointestinal adverse events were lower at up to 7.8%.
Nausea and vomiting were both frequently reported adverse events, with the highest rates of vomiting (92%) occurring in those with obesity treated with 420 mg every eight weeks and the lowest (43%) reported in the four-week dose-escalation obesity cohort, according to the NEJM data.
The gastrointestinal events were mainly limited to patients' initial dosing, Amgen noted. Either way, the data—and results from a phase 1 pharmacokinetics low-dose initiation study—“shaped our Phase 3 MARITIME program,” the company’s R&D head, Jay Bradner, M.D., said in the release.
“MariTide's monthly or less frequent dosing has the potential to improve adherence and long-term weight control, providing the opportunity to optimize health outcomes for people living with obesity, Type 2 diabetes and related conditions,” Bradner said.
Amgen’s recently initiated 72-week phase 3 MariTide studies in weight management will randomize patients to one of three target doses, putting each group at an initial starting dose of 21 mg before they move up to 35 mg and then to 70 mg over an eight-week escalation period. Both of the company's recently initiated late-stage studies, Maritime-1 and Maritime-2, have expected readouts in 2027, according to ClinicalTrials.Gov.
Although Amgen's stock is down about 5% since the ADA presentation, Jefferies analysts believe the phase 3 data will come in “better than expectations." Ultimately, they see Amgen's offering as a "player on the market” with solid efficacy and competitive dosing profile, the analysts wrote in a recent note.
Meanwhile, Mizuho Securities analyst Salim Syed thinks that the three-step dose escalation "may still not be enough" to cut down on vomiting rates in the phase 3, he wrote in a June 24 note. In a separate note, Citi Research analysts point out that while the three-step design should improve on the rate of adverse events, the strategy “detracts from the convenience narrative” of a long-acting injectable.
Still, Amgen holds firm that its candidate maintains commercial viability. The dose-escalation process is “quite simple,” the company’s head of obesity, Susan Sweeney, said on a Monday conference call with analysts. After the initial dosing schedule, patients will take a maintainable monthly therapy that has a “particular benefit” to busy primary care physicians, Sweeney added.
The company also looks to study the drug in atherosclerotic cardiovascular disease and heart failure, plus begin a phase 3 study in obstructive sleep apnea in 2025.
Based on the weight loss results of the phase 2 as well as improvements across several prespecified cardiometabolic measures, Amgen believes MariTide could be the first monthly therapy for Type 2 diabetes, which has been a “longstanding goal in the field of diabetes development,” Bradner added on the call.