Novo’s once weekly insulin win could be sweeter
Hypoglycaemia rates raise doubts again.
With analysts forecasting a stellar launch for Lilly’s diabetes newcomer Mounjaro, the group’s rival Novo Nordisk could do with a boost. And it got one on Friday with more positive pivotal data for its weekly insulin project, insulin icodec.
Still, there are questions about whether weekly insulins will gain a foothold even if they do make it to market, given worries over hypoglycaemia.
Friday’s results came from the Onwards 3 and 4 studies; data from Onwards 1, 2 and 6 were released earlier this year. In terms of blood glucose lowering all met their goal of showing non-inferiority with weekly versus daily insulin, and some also showed superiority.
However, rates of hypoglycaemia, which were previously flagged, also looked problematic in Onwards 3.
|Onwards and upwards? Results so far with insulin icodec|
|HbA1c reduction (%)||Hypoglycaemia rate (events per pt year)|
|Study||Details||Weekly insulin||Daily insulin||Weekly insulin||Daily insulin|
|Onwards 1||Vs insulin glargine, both in combo with non-insulin antidiabetics, in insulin-naïve T2DM pts||1.55*||1.35||0.30||0.16|
|Onwards 2||Vs insulin degludec in T2DM pts switching from once-daily insulin||0.93*||0.71||0.73||0.27|
|Onwards 3||Vs insulin degludec, both in combo with non-insulin antidiabetics, in treatment-naïve T2DM pts||1.57*||1.36||0.31||0.15|
|Onwards 4||Vs insulin glargine, both in combo with mealtime insulin, in T2DM pts||1.16**||1.18||5.64||5.62|
|Onwards 5||Using dose guide app vs once-daily basal insulin in insulin-naïve T2DM pts||Readout due H2 2022|
|Onwards 6||Vs insulin degludec, both in combo with mealtime insulin, in T1DM pts||0.47**||0.51||19.93||10.37|
|*Superior vs daily insulin; **non-inferior vs daily insulin. Source: company releases.|
Novo has noted that most of the trials did not show a statistically significant difference in rates of severe hypoglycaemia, defined as blood glucose below 3mmol/l, with weekly versus daily insulin. The exception to this was Onwards 6, in type 1 diabetes.
As for the latest data, the increase seen in Onwards 3 was less pronounced than that in Onwards 2, which also used insulin degludec as a comparator; furthermore, hypoglycaemia rates in Onwards 4 looked about the same between daily and weekly insulin.
But overall, the jury is out on whether convenience and slight efficacy benefits would outweigh the risk of hypos, especially since rates of the latter “are likely to increase in a real-world setting”, Jefferies analysts wrote.
They are forecasting insulin icodec peak sales of just DKK2bn ($275m).
Perhaps more excitement will be generated by the next insulin battleground, which will involve glucose-sensitive insulins; these are designed to switch on when patients’ blood glucose levels rise, and switch back off again when levels return to normal, thereby improving glycaemic control. Here, Novo is set to report data from a phase 1 trial by the end of the year.
Lilly is behind in both the weekly and glucose-sensitive insulin space. That group’s once-weekly basal insulin FC, also known as Bif, went into phase 3 this year, while the glucose-sensitive project it gained via Protomer Technologies does not yet appear to have entered the clinic.
However, for now Lilly will no doubt make the most of Mounjaro. Not only has that product impressed in type 2 diabetes, and more recently in obesity, here Novo is the laggard, with its GIP/GLP1 contender only in phase 2.
And Lilly has also touted its GLP-1 and glucagon agonist mazdutide and “triple-G” – hitting GIP, GLP-1 and glucagon – as potentially even better than Mounjaro. Novo previously discontinued a double and triple agonist on toxicity concerns.
|Basal insulin FC's pivotal programme|
|Qwint-2||Vs insulin degludec in treatment-naïve T2DM pts||Apr 2024|
|Qwint-3||Vs insulin degludec in T2DM pts already receiving basal insulin||Apr 2024|
|Qwint-4||Vs insulin glargine in T2DM pts on multiple daily insulin injections||Oct 2023|
|Qwint-5||Vs insulin degludec in T1DM pts on multiple daily insulin injections||Sep 2023|
|Note: details for Qwint-1 not yet available. Source: clinicaltrials.gov.|