It is a good thing for Sanofi that Lantus is forecast to be such a big seller, as the new formulation looks increasingly like it will only represent a minor franchise extension. Data detailed at the American Diabetes Association meeting suggest that, while Sanofi’s new insulin glargine formulation can reduce the risk of hypoglycaemia, much of the benefit might be limited to early dosing.
The French group needs to show regulators that the slower-release insulin, now called Toujeo, is differentiated from Lantus as well as from Novo Nordisk’s Tresiba when it comes to hypoglycaemia. The data so far suggest that it might not be able to do so over the long term, potentially limiting its appeal to patients and physicians.
Maintaining the benefit
Much of the topline analysis from the pivotal Edition programme for Toujeo has already been released; the ADA, however, was an opportunity for investigators to detail pooled data from three of the trials.
The Edition studies compared the new insulin against Lantus in patients also taking a short-acting mealtime insulin in Edition I, oral antidiabetic therapy such as metformin in Edition II, or any non-insulin antidiabetic therapy including GLP-1 agonists in Edition III.
The main data showed a significant 31% reduction in nocturnal hypoglycaemia rates for patients taking Toujeo, and a significant 14% reduction in hypoglycaemia rates at any time of day. Hypoglycaemia is a side effect of the glucose-lowering effects of insulin, and is most serious when it happens while diabetics are sleeping because they are unable to recognise symptoms and take steps to increase blood sugar levels – unconsciousness and even death can occur as a result.
However, UBS analyst Alexandra Hauber wrote today that the difference in hypoglycaemia rates largely occured in the weeks after patients begin taking insulin – in the “titration” phase in which patients and clinicians identify the dose necessary to keep blood glucose in the safe target range, and shortly afterwards.
Once patients enter a maintenance phase in which the insulin dose does not change, the hypoglycaemia rates do not differ a great deal, Ms Hauber wrote. On the other hand, Novo’s Tresiba in its pivotal programme did not show much difference over Lantus in the titration phase, but showed continued improvement once patients entered the maintenance phase.
“We believe that regulators (and payers) will most likely focus on the maintenance period as the key determinant of hypoglycaemia profile,” she wrote. “The hypoglycaemia rate during the titration period seems to be much more determined by variations in physician practice, rather than the fundamentals of the insulin being used. If this is indeed the case then Novo’s convincing hypo data for [Tresiba] in the maintenance phase looks to give it the upper hand.”
For branded insulin on the verge of a regulatory filing, Toujeo’s outlook remains modest for now. Few analysts have yet made an independent forecast for the product – surprising given the late stage of development and the size of the diabetic population. Leerink is alone in making a Toujeo estimate separate from Lantus – $1.2bn in 2020; others might be unwilling to make a bold call and divide the Sanofi diabetes franchise onto separate forecast lines.
Lantus surprisingly is forecast as the fourth-ranked drug by sales in the world in 2020 in spite of its expected loss of market exclusivity in 2016 (Shifts in sales forecasts leave Sovaldi on top and Januvia lagging, May 22, 2014). It has been helped along by the nature of diabetes care – switching is discouraged as long as blood sugar is in control – as well as regulatory and clinical stumbles of potential competitors.
The bigger strategic question Sanofi investors could ask now is whether, in retrospect, pursuing the newer formulation was worth it, especially given Lantus’s apparent durability. Sanofi’s Toujeo clinical programme enrolled an astounding 72,000 patients – 60% more than what Novo enrolled in trials for its two new long-acting insulins, Tresiba and Ryzodeg.
There is an element of second-guessing to that question, of course, especially given that the fate of Lantus biosimilars and competitive products could not be predicted in the middle of the last decade, when clinical work on Toujeo began. However, should it turn out to be as disappointing as the outlook now suggests, investors may clearly wonder if Toujeo was money well spent.
|Edition I||With mealtime insulin versus Lantus plus mealtime insulin||NCT01499082|
|Edition II||With oral antidiabetics versus Lantus plus oral antidiabetic||NCT01499095|
|Edition III||With non-insulin antidiabetic versus Lantus plus non-insulin antidiabetic||NCT01676220|