Amgen shares hit after analysts expose buried FDA trial halt

Thursday, Amgen posted what appeared to be a fairly innocuous update about its drug Kyprolis and other pipeline assets, but a deeper read turned up a nasty surprise.

About midway through its release, the U.S. biopharma revealed matter-of-factly that a phase 1 dose escalation clinical trial for its drug AMG 397, an oral small molecule MCL1 inhibitor, in blood cancers has been hit with a clinical hold.

The hold was handed out by the FDA given a “safety signal for cardiac toxicity.” And that’s not all: After AMG 397 showed some potential safety issues, Amgen has voluntarily halted enrollment for another early-stage test for AMG 176, given that it too is an MCL-1 inhibitor.

This is a big deal for Amgen’s pipeline, given these programs are seen as among the company’s more promising emerging oncology developments.

Shares in the company were down nearly 1% after the news was brought into the public consciousness through analysts at SVB Leerink.

In a note to clients headed “Did One of the Key Oncology Pipeline Pillars Just Crack?” the firm notes that while the exact nature of this cardiac signal in the trial was not disclosed, “animal studies suggest that loss of MCL-1 activity can be associated with sudden onset heart failure.

“Preclinical research does suggest that MCL-1 activity may be required for normal cardiac myocyte mitochondrial activity; while many adverse event liabilities are acceptable for cancer medicines, sudden onset of severe heart failure is probably not.”

It added: “So far the number of cardiac events appears to be small, but so too is the total exposure to the drugs, which raises the significance of these observations. The company has not disclosed whether other evidence of cardiac injury has been observed in the trials.

“At this stage we have not included revenue for AMG176 in our company model and valuation for Amgen; nevertheless having this product in the portfolio added to the attractiveness of Amgen’s stock and provided valuation optionality over the relatively near term. We no longer expect the company to provide new clinical data about AMG397 at this year’s ASH in early December.”