The first:
“Based on data in the briefing materials and presentations at today’s meeting, do you believe the EMPA-REG OUTCOME study results have fulfilled the recommendations laid out in the 2008 Guidance for Industry by demonstrating that use of empagliflozin to improve glycemic control would not result in an unacceptable increase in cardiovascular risk?”
Result:
– Yes – 23
– No – 0
– Abstain – 0
Interpretation – this is a given. The initial endpoint looked at non superiority (as opposed to creating a discernible benefit) and with the numbers produced in the trial, there is a clear non inferiority of Jardiance to the current SOC.
This is the important one though:
The second:
“Based on data in the briefing materials and presentations at today’s meeting, do you believe the EMPA-REG OUTCOME study results provide substantial evidence to establish that empagliflozin reduces cardiovascular mortality in the population studied?”
Result:
– Yes – 12
– No – 11
– Abstain – 0
Interpretation – the panel voted slightly in favor of the drug’s ability to reduce cardiovascular risk, but noted a few key points in support of the null hypothesis. Specifically, that they do not understand the MOA sufficiently to make such a call. We keep coming back to this, and it’s probably going to play a big part in the FDA’s ultimate decision. Additionally, the members who voted no suggested that the standard procedure for this sort of thing is that the FDA requires two Phase III studies before it can address an application. The first generally establishes efficacy. The second reinforces efficacy, and addresses any shortcomings of the first. The panel’s view on this is that without the second trial, it’s difficult to vote in favor of the hypothesis.
Conclusion – FDA Will Ask For Another Trial
So, this is what it all comes down to. What will the agency say about the application, and will it approve the drug in this expanded indication?
Our answer – no, it probably won’t. The FDA has been dragging its feet lately even on diabetes drugs with much more obvious supportive data like IDegLira from Novo Nordisk A/S (NYSE:NVO) and IGlarLixi from Sanofi SA (NYSE:SNY).
We see the two most commonly raised issues as real stumbling blocks – the lack of understanding of the MOA and the inability to address inefficiencies without a second Phase III trial.
We believe the FDA will issue a CRL and request a second Phase III trial.
Implications for Eli Lilly, Novo Nordisk, Oramed Pharmaceuticals Inc. (NASDAQ:ORMP)
The importance of this trial is not only for Jardiance and Eli Lilly alone because there are implications for other companies involved in the diabetes space. This Jardiance trial that the sNDA was based on as we noted above was a special case in that it was an extension study to see if the drug had a negative effect on cardiovascular health. The purpose of the trial was to dispel that, which it did. Since the results did seem to additionally show some cardiovascular benefit, Eli Lilly and Boehringer decided to submit an sNDA on that stroke of good fortune. If the FDA approves the sNDA, Jardiance would become the first oral type II diabetes medicine to be able to market itself as reducing the risk of cardiovascular death.
This would vastly expand its use and turn Jardiance into something much bigger than just a $38 million drug. If the FDA says that it does reduce the risk of CV death, then it would likely become a supplemental drug for most diabetics, rather than just another niche supplemental therapy option for some.
