Analysis | Amgen Has a Contender in the Weight-Loss Drug Wars

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The first detailed look at data on Amgen Inc.’s obesity drug offers a promising glimpse into the future of weight-loss treatment. How promising? Sure, it’s early days, but that hasn’t stopped investors from talking up its blockbuster potential. They may turn out to be right.

The weight loss industry has undergone a sea change in recent years. Treatments such as Novo Nordisk A/S’s Wegovy, approved in 2021, and Eli Lilly & Co.’s tirzepatide, likely to be approved next year, are allowing people to shed many more pounds than any of the options that came before them. Tirzepatide induced an average 20% reduction in body weight in its Phase 3 study — an amount that starts to put it in a category that compares to bariatric surgery.

These drugs achieve weight loss by mimicking naturally-occurring hormones called GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide). Both help regulate the release of insulin, and in turn seem to influence feelings of satiety. The first wave of weight loss drugs, such as Novo Nordisk’s Saxenda and Wegovy, work by amping up GLP-1, and Lilly’s tirzepatide turns up both GLP-1 and GIP.

Amgen’s drug, dubbed AMG-133, offers a new twist: one part of the drug, an antibody, blocks GIP, while the other part, two peptides, mimics the activity of GLP-1. The decision to block rather than boost the activity of GIP was based on a deep dive into the genetics of certain people with lower body mass indexes and, the Thousand Oaks, California-based company believes, is one key to the rapid weight loss seen in its small study.

In that Phase 1 trial, the small subset of people given the highest dose of the drug every four weeks lost about 14.5% of their body weight in less than three months. Because the study was primarily meant to understand how the drug works in humans, Amgen has yet to see that appetite-suppressing effect plateau, leaving open the possibility the drug could match or exceed the high bar set by current obesity drugs.

Meanwhile, the antibody component of the drug allows it to stick around in the body for much longer than current therapies, which are taken weekly. Just how long it can produce an effect remains to be seen, but the notion of an even longer dosing interval is appealing for a drug that will likely require chronic use. Amgen noted that “a substantial degree of weight loss was maintained beyond the treatment period,” and will present more detail on what it saw in that Phase 1 trial at a conference Saturday evening.

Amgen will start a larger, Phase 2 study in early 2023 with the goal of understanding how well the drug works over the course of a year, says Narimon Honarpour, Amgen’s vice president of General Medicine, Global Clinical Development. Other goals include seeing how AMG-133 works in a broader range of people, including, for example, those with diabetes, and exploring other ways of dosing the drug, including whether it can be given even less frequently than once a month, Honarpour says.

To stress again, the trial was very small. It’s just the first stop on the long road to approval (albeit one Amgen seems to be trying to navigate as quickly as possible). And as I’ve written before, the field has some macro issues to address around reimbursement for weight-loss drugs and questions to answer about how to manage their long-term use.

Still, it’s remarkable to see the field evolve so rapidly. Scientists spent decades trying to unravel the complex interplay of the hormones involved in our appetite, and that work is actually starting to translate into meaningful therapies.