Sanofi announced today via press release that the FDA has accepted for review its application for lixisenatide, a GLP-1 receptor agonist for the treatment of adults with type 2 diabetes mellitus. This news comes a little more than a week after the FDA rejected Novo Nordisk's application for its new long-acting insulin analogue products, Tresiba (insulin degludec) and Ryzodeg (insulin degludec + insulin aspart), for the same patient population. The key difference between these two applications? Cardiovascular outcome data.

The FDA's decision to require Novo Nordisk to complete a cardiovascular outcome trial before it would approve Tresiba and Ryzodeg runs counter to an FDA advisory committee's endorsement of the drug back in November. At that time, the FDA's panel of experts agreed that more cardiovascular data was needed but thought that the information could be obtained in post-marketing. The FDA's demand for concrete cardiovascular safety data earlier rather than later indicates that it is still reeling from the backlash surrounding Avandia and is extremely averse to being swept up in a similar controversy with another diabetes drug.

While lixisenatide's sales might not be directly impacted by the rejection of Tresiba and Ryzodeg ? lixisenatide will be the fourth to market GLP-1 receptor agonist and might not offer significant improvements in efficacy or convenience over currently marketed agents ? this is a definitive win for Sanofi in general. If Tresiba and Ryzodeg had been approved, they would have been competitors of  Sanofi's own long-acting insulin analogue, Lantus (insulin glargine), which has expected sales of $2.8 billion in the US alone in 2013. Without the introduction of these newer long-acting insulin analogues, Lantus can expect to retain the lion's share of sales for this drug class.

These recent FDA decisions also pose a significant question for other diabetes drugs currently in development ? will all novel drugs need to have initiated cardiovascular outcomes trials prior to approval? Will these kinds of trials shift from being just a point of differentiation to a requirement to play? In a market with an extremely robust pipeline (more than 400 drugs in various stages of development), this may have a profound effect on the timeline of drug development.

The FDA's higher standards will be further tested by the end of next month as it decides the fate of another novel drug in this market, Invokana. A recent FDA advisory committee voted 10 ? 5 for the recommendation to approve Johnson and Johnson's novel drug, Invokana (canagliflozin), a would-be first in class SLGT2 inhibitor. This finding comes after a previous panel found that the drug may slightly increase the risk of cardiovascular problems, including raising cholesterol levels. Like lixisenatide, Invokana does currently have an ongoing clinical trial investigating its impact on the risk for major adverse cardiac events. Will this preliminary data be enough to satisfy an increasingly cautious FDA? The agency is expected to make an announcement of its decision on March 31.

Naomi Inoshita is an Associate with the DRG Consulting group.

Sanofi Press Release: Sanofi New Drug Application for lixisenatide Accepted for Review by FDA
Novo Nordisk Press Release: Novo Nordisk received Complete Response Letter in the US for Tresiba and Ryzodeg
Pharmalot: Glaxo's Avandia Increases Heart Risks; Congress to Hold Hearings CANVAS ? CANagliflozin cardiovascular Assessment Study

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