Onglyza's label should flag heart failure risks, FDA panel says

AstraZeneca ($AZN) escaped the worst with an FDA panel vote on Onglyza. The agency's expert advisers almost unanimously backed the drug's cardiovascular safety Tuesday. But the panel also recommended that the diabetes drug's label include information about a potential risk of heart failure.

The FDA advisory committee gathered to review data from a 16,000-patient cardiovascular outcomes trial, known as SAVOR. Ahead of the Tuesday meeting, FDA staff reviewers not only flagged a potential risk of heart failure, which had already been publicly discussed. The staffers also identified an increase in the rate of "all-cause mortality" among the Onglyza patients in that trial.

According to the SAVOR study, Onglyza (saxagliptin) patients were more likely to be hospitalized with heart failure than were patients in the control arm. And the increased risk was significant--there was a 27% difference in heart failure hospitalizations between the Onglyza group and the control group.

So, the FDA asked its panelists what to do about that potential risk, even raising the question of limiting Onglyza's use or withdrawing it from the market completely. And they asked about the apparent increase in death rate among the Onglyza patients: How concerned were they about that safety signal?

Answer: Moderately so. An increase in death risk can't be ruled out, they said, according to an investor note from Evercore ISI analyst Mark Schoenebaum following the vote. But the panelists pointed out that the causes of death in the study were all over the map, a fact that muted their concern.

The panelists were more worried about the heart failure numbers, particularly in high-risk patients. But they pointed out that the SAVOR trial wasn't specifically designed to measure heart failure risks. They didn't think pulling the drug off the market--or even restricting its use--was necessary. They voted 14-1 in favor of adding information about heart failure risks to Onglyza's label.

Onglyza is a DPP-4 inhibitor, a class of drugs that also includes Merck's ($MRK) powerhouse Januvia and Takeda's newer med Nesina. Tuesday afternoon, the panel was scheduled to take a look at cardiovascular outcomes data on Nesina.

A Merck outcomes trial is set for presentation at the American Diabetes Association meeting in June, with preliminary data expected before that. If the Merck trial--which has heart failure as one of its endpoints--flags a heart failure risk associated with Januvia, then the FDA could require label changes for the entire class. That, in turn, could depress DPP-4 sales by 10% or more, analysts figure. Januvia, by far the biggest seller in the class, brought in almost $4 billion for Merck last year, while its sister combo med Janumet delivered another $2 billion. Onglyza's sales amounted to $820 million.

- here's the release
- see the Reuters story

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