Inside The FDA: Eli Lilly and Co (LLY) Jardiance Aims at Proving Cardiovascular Benefit in Diabetes, Will FDA Agree?

This reveals a market vacuum here because there currently is no oral diabetes medication proven to reduce the risk of CV death. The first diabetes company to fill this vacuum would benefit greatly. Assuming Jardiance does not get this designation in the near term, which we feel is the most likely scenario as of now, then the vacuum will likely remain for some time.

The other factor here is that it is not possible to directly test whether subcutaneous insulin therapy reduces the risk of cardiovascular death, because it would have to be tested against a control, and you cannot compare diabetics on insulin with diabetics on placebo for obvious reasons. The doubt as to whether insulin increases or decreases CV death is one of the reasons why insulin therapy is generally delayed until there is no other choice.

However, there are two companies that could conceivably fill the vacuum, assuming Jardiance does not fill it with a second Phase III trial. These are Novo Nordisk A/S (NYSE:NVO) and Oramed Pharmaceuticals Inc. (NASDAQ:ORMP). As we have pointed out in previous diabetes Inside the FDA reports, both companies are developing an oral insulin pill, and both companies have successfully completed Phase II trials with promising results. Novo’s pill seems to so far successfully lower blood sugar on par with subcutaneous insulin, while Oramed’s seems to maintain blood sugar levels over placebo.

While subcutaneous insulin cannot really be trialed against a control to test for cardiovascular benefits, an oral insulin pill can, and this opens both candidates up to the possibility of being the first insulin therapy proven to lower the chances of CV death. Trials could theoretically be designed to test oral insulin versus subcutaneous insulin on the same MACE endpoints as the Jardiance trial. This would seem appropriate in Novo’s case, whose oral therapy is showing evidence of lowering glucose levels. Novo’s pill was trialed against insulin glargine, so the same setup to test for CV risks would be consistent.

As for Oramed, it may decide to go a slightly different route of testing its own oral insulin versus placebo as it has done for its most recent Phase II trial. This would be possible in Oramed’s case because judging by the latest Phase II results, its candidate ORMD-0801 seems more appropriate for early stage or prediabetics since it seems to stabilize nighttime blood sugar rather than substantially lower it. It is conceivable to conduct a placebo-controlled trial in this case because early stage diabetics generally do not go on insulin so quickly anyway, and so a control arm could be tested against ORMD-0801 to test for cardiovascular events.

Overall, the inference here is that there is a major vacuum in the diabetes market. Insulin cannot yet be proven to reduce CV death because of the limits of testing the hypothesis, but oral insulin in theory could be tested in this way. The first company to get an oral insulin to market, whether it is Novo or Oramed, may be asked to conduct post-marketing studies just like Eli Lilly and Co (NYSE:LLY) and Boehringer conducted one for Jardiance. If either company can prove it, not only will it open up a brand new market in oral insulin, it may also be able to claim reduced chances of cardiovascular death, bringing more diabetes and prediabetes patients on insulin earlier on in their disease.

There is reason to suspect from a scientific standpoint that both Novo and Oramed’s formulations might actually do this. Since oral insulin goes directly to the liver through the portal vein, in theory it acts as insulin acts in normal healthy people. This in itself implies that it might reduce CV death, which would make either pill a big hit in diabetes markets.

Yet another reason why oral insulin could change the diabetes landscape.

Note: This article is written by David Rich and originally published at Market Exclusive.