Novo Nordisk's Tresiba Fails to Meet Primary Endpoint in Head-to-Head Trial Against Sanofi's Toujeo

Compiled by Fan Dongdong

Currently, Novo Nordisk’s Tresiba (insulin degludec) is vying with Sanofi’s Toujeo (insulin glargine U300) for dominance in the next-generation basal insulin market. Although Novo Nordisk has long hoped to stand out in this competition, the latest trial results have been disappointing.

On September 19 local time, Novo Nordisk announced at the European Association for the Study of Diabetes (EASD) Annual Meeting that Tresiba missed its primary endpoint in a pivotal head-to-head trial against Sanofi’s Toujeo. The results showed that, compared with Toujeo, Tresiba failed to significantly reduce the number of hypoglycemic events in patients during the 36-week maintenance period. Novo Nordisk stated that although the Tresiba treatment group did experience fewer hypoglycemic events than the Toujeo group, the difference between the two drugs did not reach the threshold for statistical significance.

However, Mads Krogsgaard Thomsen, Chief Scientific Officer at Novo Nordisk, appears to offer a different interpretation. He believes that the failure of the trial to meet its primary endpoint was not due to the drug itself, but rather attributable to the presence of one or two patients with more severe hypotension in the Tresiba treatment group.

Novo Nordisk also pointed out that, compared with Toujeo, Tresiba can reduce the incidence of severe hypoglycemia by 80%, and reduce the incidence of nocturnal hypoglycemic events in diabetic patients by 37% within 36 weeks.

Sanofi does not agree that the results of this trial negate the therapeutic advantages of Tresiba. David Werner, Global Head of Insulin at Sanofi, stated prior to the release of the results, “It is difficult to draw any conclusion other than failure from this comparative trial.”

Werner added that Sanofi had previously conducted a head-to-head study named Bright, stating, “We have demonstrated that Tresiba and Toujeo share more similarities than differences.” In June this year, at the 79th Scientific Sessions of the American Diabetes Association, Sanofi presented comparative analysis data against Tresiba. The results showed that in patients with type 2 diabetes and moderate to severe renal impairment, Toujeo was superior to Tresiba in glycemic control (1.72% vs. 1.3%), without increasing the risk of hypoglycemia.

Among Sanofi’s marketed diabetes products, Lantus and Toujeo are undoubtedly the two most important assets; however, external forecasts predict that sales of both drugs will continue to decline in the coming years. As the world’s first long-acting insulin analog, Lantus has dominated the diabetes market for many years, but its patent in the United States expired four years ago (in February 2015). As an upgraded version of Lantus, Toujeo is currently the most significant asset in Sanofi’s diabetes pipeline. In 2018, Toujeo achieved sales of $840 million, yet this underwhelming performance was insufficient to effectively offset the revenue shortfall from Lantus. Due to factors such as the expiration of patent protection, Lantus’s sales decreased from $4.63 billion in 2017 to $3.57 billion in 2018.

Toujeo’s top competitor, Tresiba, was approved for market launch in September 2012. This ultra-long-acting basal insulin, actively developed by Novo Nordisk, offers great convenience with once-daily dosing and provides glycemic control lasting over 42 hours. In comparison, Tresiba has demonstrated stronger sales performance, achieving $1.22 billion in sales in 2018.

In its 2018 annual report, Novo Nordisk stated that it held a 46.4% share of the global insulin market and a 45.2% share of the next-generation insulin market, underscoring its dominant position in the worldwide diabetes market. However, in the increasingly competitive landscape of diabetes care, sustaining such dominance is no easy feat, requiring continuous innovation and an ever-evolving product portfolio.

In March this year, Novo Nordisk submitted two applications to the U.S. FDA for semaglutide, seeking approval for its use in reducing the risk of major cardiovascular events in patients with type 2 diabetes and for its approval as an adjunctive treatment alongside diet and exercise. Since the application for adjunctive therapy was granted priority review, a specific response from the FDA is expected within six months, i.e., by the end of this month. If semaglutide ultimately receives approval, it will become the first globally approved oral GLP-1 receptor agonist.

Reference Source: Novo Nordisk's Tresiba Misses Main Mark in Head-to-Head Trial with Sanofi's Toujeo