Amgen is axing obesity candidate AMG 786 and going all in on later-stage asset MariTide.
“Given the profile we've seen with AMG 786, we will not pursue further development,” Jay Bradner, M.D., Amgen’s executive vice president of R&D and chief scientific officer, said on the company’s first-quarter earnings call. “Instead, in obesity, we're differentially investing in MariTide and a number of preclinical assets.”
Little information was shared about the terminated small-molecule program, with a Friday release revealing only that a phase 1 clinical trial assessing AMG 786 “is complete."
Amgen has been tight-lipped about AMG 786 since its inception. According to ClinicalTrials.gov, the phase 1 trial was designed to evaluate the safety and tolerability of the small molecule among healthy participants and participants with obesity. The double-blind, multiple ascending dose study had an estimated enrollment of 72 patients.
“The differentiated profile that we're seeing with MariTide really raises the bar for Amgen obesity medicines, and the profile for 786 just did not meet that bar in our assessment,” Bradner said on Friday’s call in response to a question about the company’s broader obesity portfolio. “We do have a pipeline—a strong pipeline—of earlier assets. They're incretin- as well as nonincretin-based; some are injectable and some are oral.”
MariTide, a GIPR antagonist conjugated to two GLP-1 analogues, now stands in the limelight. The obesity candidate, previously dubbed AMG 133, is currently being assessed in a phase 2 dose-ranging study among participants who are overweight or with obesity, with or without Type 2 diabetes.
Members of Amgen leadership have viewed an interim analysis of the phase 2 study.
“Following the interim analysis, I would say we're confident in MariTide’s differentiated profile and believe that it will address important unmet medical needs,” Amgen CEO Bob Bradway said on the call.
However, the company, once again, remains tight-lipped. The majority of questions during the earnings call revolved around MariTide, and the majority went unanswered.
“This is an ongoing study, so we have to be careful to avoid in introducing an inadvertent bias or blinding,” Bradner said. “And so, we just can't comment on individual characteristics.”
Amgen expects to share top-line 52-week data from the 11-arm phase 2 study in late 2024, according to Bradner.
Like Eli Lilly’s obesity drug Zepbound, MariTide modulates appetite and insulin secretion by targeting the receptors for the hormones GLP-1 and GIP. But, while the drugs are both agonists of the GLP-1 receptor—the target of Novo Nordisk’s Wegovy—Zepbound and MariTide differ in how they act on the GIP receptor. Zepbound is a dual agonist of the GLP-1 and GIP receptors, meaning it increases their activity, while 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.
While it’s unclear exactly what type of device MariTide will be delivered in, Bradner described administration via a “convenient, handheld, patient-friendly autoinjector device with a monthly, or even less frequent, single injection administration.”
The company is actively planning a broad phase 3 program, including obesity, obesity-related conditions and diabetes, for MariTide, according to CEO Bradway.
The company is also slated to launch an additional phase 2 trial investigating the obesity asset specifically for patients with diabetes, with and without obesity.
William Blair analysts said they have grown more confident overtime with MariTide's potential to meaningfully differentiate from other therapies in development, particularly in regard to treatment intervals, according to a May 3 note.
"We see MariTide as having multi-blockbuster potential despite needing to penetrate the current duopoly with significant competition in clinical development, and we believe Amgen has the capacity and expertise to maximize development of the asset," the analyst wrote.
Editor's note: This article was updated at 10 a.m. on May 3 to include analysis from William Blair.