Novo Nordisk suffered a major blow at the end of last week after the US FDA rejected its marketing application for two new diabetes drugs at the heart of its growth ambitions.
The agency issued a Complete Response Letter to the Danish pharma company last week, indicating that the applications for Tresiba (insulin degludec) and Ryzodeg (insulin degludec/insulin aspart) cannot be approved in their current form.
Novo Nordisk issued a terse statement yesterday (February 10) to acknowledge the letter, which comes despite a vote in favour of approval of the two drugs by the FDA's own advisory committee last November, as well as approvals for the products in the EU, Japan and Mexico.
The FDA's advisory committee had voted 8 to 4 in favour of approving the product with a recommendation for cardiovascular outcomes trial post-approval, but the regulator has now decided that it requires additional proof of the products' safety via a cardiovascular outcomes trial ahead of registration. That could delay a US launch by two years or more.
In its briefing document released ahead of the panel meeting, the FDA pointed to the occurrence of a cardiovascular "safety signal" in Novo Nordisk's dataset. The agency's reviewer noted that "a meta-analysis of 16 phase III trials … estimated that use of degludec products could increase the composite risk of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and unstable angina by 10 per cent relative to active comparators".
Novo Nordisk is hoping that Tresiba can topple Sanofi's €4bn-a-year blockbuster Lantus (insulin glargine) from its dominant position in the basal insulin market, where it has an 80 per cent market share. The company says that insulin degludec has a very long and predictable pharmacological action profile - meaning it can be delivered at any time of day - as well as a lower tendency to cause low blood sugar (hypoglycaemia) than Lantus.
Ahead of the FDA decision analysts had predicted that Tresiba and Ryzodeg could reach sales of up to $4bn at peak, but the delay in US approval could allow competing products to close the gap on Novo Nordisk.
A particular threat is Eli Lilly's LY2605541 which is in phase III testing and like Novo Nordisk's drug has shown advantages over Lantus, including a greater tendency to cause weight loss and reduce the risk of hypoglycaemia.
Novo Nordisk has said it expects to launch Tresiba in the UK and Denmark during the first half of this year and in other European markets throughout the rest of 2013 and 2014, and told analysts in its fourth-quarter results statement that it was expanding its US salesforce to prepare for global launch.
Meanwhile, the FDA's decision also casts a shadow over the development of IDegLira, a combination of insulin degludec and the active ingredient in Novo Nordisk's Victoza (liraglutide) which is due for filing in the EU in mid-2013.