- Novo Nordisk expects the Food and Drug Administration to decide by early next year on whether the drugmaker can sell its diabetes injection Ozempic and a related oral formulation as protective of heart health.
- Neither of the two drug versions have completed long-term cardiovascular outcomes studies on the scale of their main competitor, Eli Lilly's Trulicity, but Novo executives believe the "totality of evidence" collected so far will win the FDA's favor.
- The company released the final piece of evidence in that case at the American Diabetes Association meeting Tuesday, unveiling study results that show the oral formulation of Ozempic's main ingredient, semaglutide, to be statistically similar to placebo on cardiovascular safety. The study is not as large as Lilly's REWIND trial of Trulicity, and thus was not able to demonstrate a statistically significant benefit, although patients taking the Novo drug had numerically fewer heart-related complications.
Novo Nordisk and Eli Lilly are frequently fighting for market share in diabetes. In the relatively new class of GLP-1 agonists, Trulicity (dulaglutide) has had momentum on its side thanks to once-weekly dosing, compared to the once-daily injections for Novo's older Victoza (liraglutide).
Trulicity posted sales of $3.2 billion in 2018, compared to Victoza's $3.6 billion.
A winning marketing formula in diabetes is an agent that can reduce heart complications, the main cause of death associated with the disease, as well as lower blood sugar. This is an edge that Victoza had over Trulicity, although that could fade thanks to the results of the REWIND trial.
Enter semaglutide, the Novo drug now sold as a once-weekly injection under the brand name Ozempic. It's also under review as a once-daily pill intended to challenge Trulicity.
However, Ozempic's approval in late 2017 means it is too new to have completed the size and scope of clinical research typically necessary to tease out the 12% to 13% reduction in the risk of heart attack, stroke or cardiovascular death shown by Victoza and Trulicity, when compared with a placebo.
Novo thinks it has an answer: combining cardiovascular safety data collected so far into one big data set. Ozempic demonstrated that it reduced the risk of heart-related complications and death by 26% in a trial called SUSTAIN that had one-third the number of patients as REWIND and lasted less than half as long.
Today's data for oral semaglutide came from PIONEER 6, which had a similar patient population and follow-up time, and demonstrated that the patients taking semaglutide were not at cardiovascular risk when compared with those taking a placebo. Of patients taking oral semaglutide, 3.8% experienced a cardiovascular event, compared with 4.8% of those taking a placebo.
Todd Hobbs, Novo's North American chief medical officer, acknowledged that the data set supporting the semaglutide cardiovascular outcomes application is not as rich as that of Trulicity with REWIND or Victoza's LEADER trial.
LEADER, for example, recorded 1,100 cardiovascular events in 9,300 patients over more than four years of study, while the two semaglutide trials have so far recorded 391 events in 6,500 patients for two years or less. Other cardiovascular trials in diabetes have been even bigger, with the DECLARE-TIMI trial of Farxiga (dapagliflozin) topping 17,000 patients.
But when Ozempic faced an FDA advisory committee, the expert panelists were sympathetic to Novo's cardiovascular aspirations.
"They felt SUSTAIN 6 was a robust study that was statistically significant in terms of [cardiovascular] events, but they felt it wasn't quite enough," Hobbs told BioPharma Dive in an interview. "We're adding to that body of knowledge with PIONEER 6."
In any case, Novo is readying a longer-term trial of oral semaglutide called SOUL that will begin enrolling 9,600 patients this summer.
The only problem is that if follow-up takes up to five years, as the trial design suggests is possible, Trulicity's marketing edge could be substantial should the FDA ultimately decide against Novo's current cardiovascular submission.