FDA delivered bad news to Novo Nordisk and good news to Celgene in separate decisions Friday on applications for marketing new drugs.
The agency threw a curve to Novo by insisting on another clinical trial assessing the cardiovascular risk of its two new adult diabetes drug candidates, Tresiba® ( insulin degludec) and Ryzodeg® (insulin degludec/insulin aspart) in a Complete Response Letter sent to the company on February 8.
FDA’s action came less than a month after the European Commission granted Novo approval across all 27 European Union member states for the drug candidates. Novo has said it expects to launch Tresiba in the U.K. and Denmark during the first half of this year, and in other European markets throughout the rest of 2013 and 2014. Ryzodeg is expected to be launched about one year after Tresiba rings up its first sales.
The FDA decision was surprising since the agency spurned the recommendation of an advisory committee. The Endocrinologic and Metabolic Drugs Advisory Committee in November recommended agency approval of Tresiba after concluding Novo showed sufficient efficacy and safety data to support marketing degludec for use alone or in combination with an insulin boost for blood-sugar control during meals. The recommendation led Novo’s CSO Mads Krogsgaard Thomsen to tell Bloomberg at the time the company was looking to obtain full FDA marketing approval in the first half of this year.
But the panel vote on recommending approval was 8–4. By contrast, the advisory committee came down unanimously on recommending that Novo conduct a trial to examine the heart safety risks of Tresiba.
And worse for Novo, FDA tied any future approval of the drug to the company resolving complaints the agency made in a warning letter Dec. 12, 2012. FDA said Novo failed to prevent microbiological contamination of drug products; and failed to investigate whether a failed batch had been distributed from its manufacturing plant in Novo Alle, Bagsvaerd Denmark, based on a March 12-20, 2012, inspection there by agency inspectors.
In the letter, FDA warned: "Until all corrections have been completed and FDA has confirmed corrections of the violations and your firm’s compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug product manufacturer."
Addressing analysts today on a conference call, Novo CEO Lars Rebien Soerensen said: “It’s not a good day for diabetes patients in the U.S., it’s not a good day for Novo Nordisk and for Novo Nordisk shareholders,” according to numerous news reports, adding that the company cannot likely provide the heart safety data this year or in 2014.
Shareholders showed their displeasure through a selloff that lowered Novo's share price as much as 17% in Monday morning trading.
According to Novo Nordisk, Tresiba has a duration of action beyond 42 hours, making it the first basal insulin to offer patients the possibility of adjusting their time of injection. Ryzodeg can be administered once or twice daily with the main meal(s).
Tresiba and Ryzodeg are two key components in Novo Nordisk’s plans for a beachhead in the long-acting basal insulin segment of the diabetes drug market. The segment is now dominated by Sanofi, whose Lantus (insulin glargine) has grown to a market share estimated at 80% and blockbuster-level annual sales.
Sanofi reported blockbuster results for Lantus last week: Q4 sales of the drug zoomed 22.6% from the final three months of 2011, to about €1.4 billion (nearly $1.8 billion). For all of 2012, sales jumped 19.4% over the previous year, to €4.96 billion ($6.6 billion).