Why IGlarLixi Was Delayed
The FDA panel vote for IGlarLixi was overwhelmingly in favor of approval by a vote of 12 to 2. This is because, just like IDegLira, the data for IGlarLixi was very impressive with similar benefits. Nevertheless, nearly every single panelist expressed serious concerns over the delivery device.
First, in an effort to leapfrog Novo Nordisk and make their product better, Sanofi decided to use two different pens, one for a low dose combo, and another for a high dose. They may have thought that by having two pens it would open up more patient populations, as those with higher insulin resistance would be able to use the higher dose pen. This would not be an option with IDegLira of course.
Sanofi SA (ADR) (NYSE:SNY) was perhaps too ambitious here.
What ended up happening was that the panelists, even the ones that voted for approval, were universally concerned about the pen due to the potential for dosage confusion. Panelists raised these same concerns with IDegLira, but since there was only one delivery pen, the concerns were not as potent as with IGlarLixi. The reasons for each vote on IGlarLixi are given on page 380 on this document where you will find that nearly every panelist expressed the same concern over the delivery pen confusion potential.
Particularly, the concerns were based on a Human Factors Study that showed that 1 out of 15 pharmacists erred in regard to the dosage and gave a patient the wrong pen. Further, 1 out of 45 nurses had trouble identifying which pen corresponded to which dose. Had Sanofi been a little less ambitious and stuck with one pen only, the delay would probably never have happened.
As it is now, the question of whether IGlarLixi gets approved depends on whether there is a quick fix to this problem. The best case scenario is that Sanofi changes the color on the pens or something to make it more obvious which is which and the FDA OK’s it. This is problematic, because another Human Factors study may be required to corroborate the effect of any change, and that will take time. Sanofi doesn’t have that data yet.
The worst case scenario is that Sanofi simply nixes one of the pens for now and sticks with the lower dose pen, dealing with the higher dose pen later when more Human Factor studies can be conducted. In such a case it is very likely that IGlarLixi with only one pen will be approved.
Conclusions
From these documents, the implications for other diabetes companies are as follows. First, dosing confusion is crucial. Companies need to make sure that their delivery products are clear, and units are understood, and also that one unit does not apply to two different drugs. These are actually mutually contradictory, so best to stick with no units it seems.
There is a Catch 22 here because IDegLira has no units and looks like it will be approved without additional delay, but IGlarLixi has units for the insulin component that can be confused with the GLP-1 component, and this was considered a serious problem by panelists as well. Best to keep the units unlabeled, and stick to a simple device without trying to get too clever.
Second, FDA panelists for diabetes drugs are most impressed by lack of weight gain, patient compliance, and ease of administration. The implications for oral insulin being developed by both Novo Nordisk A/S (ADR) (NYSE:NVO) and Oramed Pharmaceuticals are positive, because these therapies may cause less weight gain because the insulin is delivered to the liver through the portal vein, and will probably increase compliance. Whether or not they are as effective as subcutaneous insulin appears at this point to be less of an issue, as long as they are somewhat effective.
Third, counting the votes by itself is not sufficient to determine what the FDA will actually do in response. As we can see here, the vote for IGlarLixi was 12-2, and still the FDA delayed its review at great cost to Sanofi SA (ADR) (NYSE:SNY). The reasoning behind each vote is critical, and the writing was on the wall.
Fourth, for any company pursuing a combination drug in general, synergy does not seem to be required. An additive effect appears to be sufficient.
Note: This article is written by David Rich and was originally published at Market Exclusive.
