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Obesity drug mania takes over Amgen’s earnings call

Amgen is a global pharmaceutical company worth more than $160 billion. Nine of its marketed medicines are blockbuster products by annual sales.

Yet, on a Tuesday conference call discussing Amgen’s fourth quarter earnings, all Wall Street analysts wanted to talk about was an experimental drug that only just cleared the first stage of human testing.

More than half of the questions asked by analysts were focused on AMG 133, a promising treatment for obesity that’s drawn attention as a potential competitor to in-demand weight loss medicines from Novo Nordisk and Eli Lilly. While Wall Street often overlooks the present to focus on the future, the intense interest in a drug years away from the market was noteworthy.

“Today was not a routine earnings call,” wrote Umer Raffat, an analyst from Evercore ISI, in a note to clients Tuesday evening.

Analysts’ scrutiny of AMG 133 is a byproduct of surging demand for so-called GLP-1 drugs like Novo’s Wegovy and Lilly’s Zepbound. Amgen’s drug also targets GLP-1, a gut hormone that regulates insulin secretion and is thought to play a role in signaling satiety, or fullness.

Estimates for size of the GLP-1 drug market have soared as clinical trial results have shown Wegovy and Zepbound can reduce body weight by 15% to 20%. More recent data has indicated GLP-1 drugs can reduce heart and kidney disease risk, as well as potentially treat a common liver illness. Some analysts expect total GLP-1 sales to reach as high as $100 billion.

That lofty potential has lured many companies into obesity drug research, including Pfizer, Roche, AstraZeneca and Boehringer Ingelheim. With AMG 133, Amgen is in the mix, too, and the drug’s advancement through testing has contributed to a run-up in the company’s stock.

On Monday, results from a Phase 1 trial of the drug were published in Nature Metabolism, expanding on data previously shared by Amgen. They show that a high dose of AMG 133, given monthly, can reduce body weight by up to 15%, with weight loss sustained through several months.

But the paper also detailed caveats, including participant drop out rates in one of the study’s arms, a high rate of gastrointestinal side effects and an uneven effect on levels of cholesterol and triglycerides.

Analysts pressed Amgen executives on these questions Tuesday, probing what Jefferies’ Michael Yee called the “most scrutinized Phase 1 publication.” In particular, analysts were keen to assess how AMG 133 might stack up against either Wegovy or Zepbound, which are both once-weekly injections.

Jay Bradner, Amgen’s new head of research and development, pushed back against some of analysts’ concerns, such as AMG 133’s inconclusive effect on lipid measurements.

“I would just caution that this is a Phase I trial, the numbers are very small, that the duration of treatment is rather short,” Bradner said. “We take no concern whatsoever from those measurements on the study.”

Amgen executives also defended the design of AMG 133, which in addition to activating GLP-1 is designed to block another hormone receptor called GIP. That mechanism of action is opposite to Zepbound, which activates GIP as well as GLP-1.

Amgen has pointed to genetics data suggesting that blocking GIP could be helpful in delivering greater body weight reductions. “We feel very secure in our choice to inhibit that receptor,” said Amgen CEO Robert Bradway on Tuesday’s call.

Still, the conflicting approaches pose a unique test for Amgen to prove its design is better. (Wegovy doesn’t target GIP.)

“With Eli Lilly and Novo so far ahead, the burden will be with Amgen to differentiate,” wrote Mizuho analyst Salim Syed in a Tuesday note to clients.

Amgen will have a chance toward the end of this year, when it’s expecting to disclose results from a Phase 2 study of AMG 133. The company recently added a second part to this trial to test weight loss reductions beyond one year.

Before then, Amgen will report early trial data on another drug for obesity, AMG 786, that works in a different way than AMG 133.

For Wall Street, the question has become how much Amgen’s current value already reflects the potential for its obesity drugs to compete with Wegovy and Zepbound.

“Depending on who you talk to, AMG 133 makes up $50, $100, $320 of Amgen’s current valuation based on their Phase 1 data and the potential for this incretin targeting drug to be the better mouse trap vs. Lilly and Novo’s tirzepatide and semaglutide,” wrote Baird analyst Brian Skorney in a research note.

Amgen shares, which hit an all-time high Feb. 1, fell by more than 4% Wednesday.