Going into another head-to-head diabetes drug showdown with Sanofi, Novo Nordisk’s regulatory team will need to spend some time next Tuesday explaining to an FDA advisory panel just how it designed a big late-stage program for its combination of Tresiba (insulin degludec) and Victoza (liraglutide), a once-daily injectable dubbed IDegLira.
That combination of a GLP-1 drug and basal insulin proved superior to either of the two treatments provided to patients alone, according to Novo. But an internal assessment at the agency concluded that the trial design was biased in favor of the combo, making it impossible for the FDA to agree on that point regarding its superiority to Tresiba.
IDegLira is widely considered a key product for Novo, which is an aggressive player in the high-stakes battle over a growing multibillion-dollar global market. The combo was held up by a serious delay on Tresiba, which was approved in the U.S. last fall after a two-year delay.
Analysts have pegged peak sales of IDegLira, already approved in Europe as Xultophy, at around $1 billion. The big idea here is that a combo would provide diabetics a better way to control blood sugar while eliminating some of the complications associated with insulin use.
This combo--which also distinguished itself against Sanofi’s megablockbuster Lantus--will be aimed at a huge market, which means every point raised by the FDA will loom large at the FDA panel review. And that will call for a close look at the trial design.
“Evaluations of the proportion of subjects who reached titration targets and the relative time needed to reach dose stabilization demonstrated that the titration algorithm resulted in a lag in both the proportion of subjects reaching glycemic targets and the time to reach dose stabilization in the comparator insulin arms of the trials, such that the HbA1c comparison between study arms was biased,” the agency’s review noted. “Further, 26-week comparator HbA1c did not reflect a period of preceding glycemic stability. Due to these trial design concerns we are not able to conclude that IDegLira is superior to IDeg, as the Applicant has concluded. To reach such a conclusion, a trial in which both arms were dosed and titrated in a maximally effective and balanced manner would be needed.”
The reviewers also weren’t happy that the combo allowed for lower doses of liraglutide than had proved efficacious alone. The safety review also concluded that patients taking the combo would be subject to adverse effects associated with both treatments instead of just one.
Right behind Novo, Sanofi is lining up for an FDA panel on iGlarLixi, a combination of Lantus with the GLP-1 drug Lyxumia (lixisenatide), now under review.
- here's the review