Pipeline therapies within the cardiometabolic space have recently gathered interest following the 20th World Congress of , Diabetes and Cardiovascular Disease (WCIRDC) Hybrid Conference, which took place on 1–3 December. The spotlight was placed on many up-and-coming pharmacotherapies within the space, one of which was obesity therapy, AMG-133, following the company’s announcement of its Phase I therapy results last week, on 1 December.
AMG-133, which has completed Phase I of development for obesity (NCT04478708), is of paramount interest as it is a first-in-class therapy for obesity. Clinical trial results in obese patients showed that by Day 85 of the study, participants in the multiple ascending doses (MAD) cohort showed a mean percentage change in body weight of -14.5% at its maximum dose of 420mg, displaying efficacy comparable to Wegovy (semaglutide), which is on the market, and Mounjaro (tirzepatide), which is approved for type 2 diabetes and currently under fast-track designation for obesity, with approval anticipated in April 2023.
AMG-133 targets glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) in a novel bispecific mechanism fashion. While AMG-133 shares the same targets as tirzepatide, AMG-133 conversely antagonises GIPR instead, thereby offering a unique feature within the obesity market. Studies have shown that in combination with GLP-1R agonism, both agonism and antagonism of GIPR promote weight loss. Furthermore, AMG-133 is a longer-acting therapy, thus significantly reducing the number of treatment days in comparison to the currently marketed and late-stage pipeline therapies: while tirzepatide requires weekly administration, AMG-133 is administered once every four weeks (Q4W), which has positive implications on patient compliance.
Currently, patients who are prescribed the standard of care, Wegovy, are expected to self-administer treatment on a weekly basis. Furthermore, many patients receiving treatment for obesity have other comorbidities that they must also tend to, so this reduction in treatment days is all the more essential to this subset of patients in ameliorating compliance to treatment. Key opinion leaders (KOLs) interviewed by GlobalData have expressed that while many therapies in the pipeline are essentially me-too drugs, comprising GLP-1 agonists and an additional mode of action to produce a dual or triple incretin-type mode of action, they still show potential in being effective.
Despite AMG-133 being a latecomer into the incretin mimetic space, its unique features set it apart from currently marketed therapies. While it is still too early to comment on the efficacy of AMG-133, its practicality shows the potential for it to be favoured among many patients and clinicians alike should it reach the obesity market. If its Phase II trial, which is set to start early next year, and subsequent trials yield good results upon completion, this new therapy may be on course to compete directly with the standard-of-care therapies across the obesity space.
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