Nevertheless, we can speculate as to what’s going on here, and that it may in fact be synergy. Since GLP-1 drugs are glucose-dependent and cause the pancreas to produce insulin in a glucose-dependent manner, what seems to be happening here is that the liraglutide component is obviating the need for more insulin, thereby slowing the insulin dosage escalation. The fact that everyone in the panel was sidestepping this elephant in the room just illustrates the overly cautious nature of these panels more than anything else.
Whether this interaction can technically be called synergy is a nomenclature question and not all that important. Keep in mind that FDA panelists are not FDA officials and usually not so bureaucratically-minded. Meaning, regarding their vote, many of them (not all) don’t particularly care if something meets a technical definition or not as long as they can see and understand an obvious effect, regardless of what it’s called. This, at least, is our opinion.
Dosing Questions
What seemed to be among the more pressing issues for the panelists was the dosing question. There are no units on the IDeglira pen that administers the drug. The panelists wanted units so patients can know how much of what they are putting into their bodies, and they wanted it clearly labeled as two drugs so patients don’t go adding insulin to IDegLira, which could result in an insulin overdose. In the end though, none of the panelists saw this as outweighing the benefits.
Reasoning Behind Each Vote And Implications
At the end of the meeting, each panelist was asked to provide a reason for their vote. The vote was unanimous in favor or approval. As we will see, the reasons provided did serve as a warning for the eventual delay of Sanofi’s IGlarLixi, which we’ll see even more of in the reasons provided for that combination drug. We won’t go into every vote, but key lines only.
One panelist, not a clinician but a patient representative, was particularly impressed with the idea of patient compliance due to one shot over two separate ones. Keep in mind that patient compliance was never actually tested. It is only an intuitive assumption, and yet it was key in inspiring a yes vote.
Another panelist, one Dr. Charlie Stanley, a pediatric diabetologist, also said something key for any future oral insulin product:
I voted yes. I mean obviously, as a pediatric diabetologist, I don’t have a 1 lot of experience with these agents for type 2 diabetes. I would love to see a 12-month plus weight data for this combination product because we really may be entering an era where that could have tremendous application with an insulin that perhaps even beyond 12 months, that the patients don’t gain weight the way people do on other insulin types of regimens.
The first thing to note about this is that children with diabetes, early stage of course, are not generally prescribed insulin or GLP-1. This is why he has little experience with the drugs. Second, he is particularly excited about the lack of weight gain from the combination versus insulin alone. If combining the therapies prevents weight gain, he sees this as a “new era”. This is significant because oral insulin would take care of both these issues and indeed usher in a new era.
First, it would allow insulin to be prescribed to early stage diabetic children due to the relative ease of taking a pill over injection. Second, oral insulin is theorized to prevent weight gain as well, some evidence of which we have seen in Oramed’s Phase II data for its own oral insulin formulation.
In other words, if it can be shown for either Novo Nordisk or Oramed or both that an oral insulin enables insulin therapy at a younger age and prevents weight gain, any FDA panel is likely to be very impressed, whatever the other drawbacks of an oral insulin may be.
Most of the panelists, despite their yes votes, expressed concerns over the lack of units and dosing questions. Those concerns were simply overridden by the good data. This, as we’ll see ahead, was a red flag for Sanofi’s IGlarLixi.
