The 10% surge in Novo Nordisk's shares today can be taken as a sigh of relief from investors after it emerged that long-acting insulins Tresiba and Ryzodeg could be launched in the US by the end of 2015.
The Danish group announced that it would re-submit its US application within the next month on the strength of interim cardiovascular outcomes data from the Devote trial, which was requested by the FDA after its rejection in 2013 to rule out significant cardiovascular risk. Now Novo needs a quick-time regulatory timetable to ensure that it can put the two diabetes treatments into US patients’ hands before the market is too disrupted by aggressive discounting by competitors Sanofi and Lilly.
Novo revealed little more than that it would be re-submitting the two diabetes agents based on interim data, and this silence came as no surprise to the sector. The company is being purposefully opaque – the Devote analysis is known only to an internal team of unblinded researchers, and it was left to them to decide whether to send it to the FDA now or wait until late 2016 (Event – Novo needs Tresiba launch sooner than later, March 2, 2015).
In structuring its regulatory strategy this way Novo will avoid the wrath visited on Orexigen after it controversially disclosed interim cardiovascular data from its Light trial of Contrave comparatively widely, a choice that will influence whether the benefit shown so far can be sustained.
This was exactly the balm Novo needed to counteract disappointing data from its ultra-fast acting insulin FIAsp, announced a day before the Tresiba re-submission. Facing competitive pressure on its core insulin franchise, the group has been hoping to generate new growth through development of better products. Unfortunately, FIAsp will probably not be the answer as its performance does not look much better than Novo's biggest product, NovoRapid.
Tresiba and Ryzodeg now look like they have a fighting chance of helping Novo defend its all-important franchise, however. Should the FDA quickly approve on this data, Novo will trail Sanofi’s latest move in the long-acting insulin space by close to a year, but it could at least precede biosimilar competition.
Sanofi’s move is launch of Toujeo, meant to cushion against losses when Lantus loses market exclusivity next year and Lilly’s biosimilar Basaglar begins taking market share. However, as a slower-release version of Lantus, Toujeo has struggled to show that it is meaningfully different, and the FDA label gives physicians little reason to prescribe the new agent (Meet the new Lantus, same as the old Lantus, February 26, 2015).
Of course, it would have been timelier for Novo to have launched Tresiba and Ryzodeg – a combination of Tresiba’s active ingredient, insulin degludec, with short-acting NovoRapid – in 2013, before payers began pushing for deeper discounts and Toujeo could launch. Still, a launch this year should be helpful in meeting consensus expectations of $1.5bn in Tresiba sales and $519m in Ryzodeg sales worldwide in 2020.
On the label
What will probably be crucial to avoid the Toujeo trap is for Tresiba to earn an FDA label showing a hypoglycaemia benefit. This is what Novo pressed for in its original application, although an FDA advisory committee suggested that the main benefit was in nocturnal episodes, which can go unnoticed and lead to greater complications.
The European Medicines Agency has acknowledged this benefit, but this is no guarantee that the FDA will. It does not help Novo’s case that its phase III programme allowed Tresiba daily doses to be advantageously timed. The Devote data set should, however, provide further analysis that could sway the regulator’s opinion one way or another.
Assuming the new insulins are approved, the label decision will define Novo’s launch strategy. With a safety benefit, Tresiba and Ryzodeg can plausibly be positioned as premium products that can get onto physicians' prescription pads with persuasive marketing. Otherwise, they risk being seen as me-too agents that will need to earn their way onto formularies with favourable pricing.