Tresiba Vs. Lantus: Novo Nordisk Scores A Win In Second Head-To-Head

Novo revealed top-line results from SWITCH 1, showing Tresiba was superior to Lantus on a secondary endpoint of severe hypoglycemia in the maintenance period in type 1 diabetics, a positive after Tresiba failed to show superiority on the endpoint in another trial, SWITCH 2, in type 2 diabetes.

Novo Nordisk AS’ next-generation long-acting insulin Tresiba (insulin degludec) may get an edge competing against Sanofi’s venerable Lantus (insulin glargine) over Sanofi’s own next-generation basal insulin Toujeo (insulin glargine) after it showed superior hypoglycemia benefits versus Lantus in the second of two head-to-head trials.

Whether the incremental benefit seen with Tresiba or Toujeo will be enough to pit the newer insulins competitively against Lantus, especially as cheaper biosimilar copies of the insulin become available, remains the larger question.

Novo announced Feb. 24 top-line data from SWITCH 1, the second of two head-to-head clinical studies comparing the safety and efficacy of Tresiba to Lantus, with an emphasis on hypoglycemia. SWITCH 1 enrolled 501 people with type 1 diabetes, while SWITCH 2 studied 721 people with type 2 diabetes. Novo already reported the top-line data from SWITCH 2 Jan. 29 (Also see "Novo Nordisk Says Global Payer Pressure Limits Price Rises" - Pink Sheet, 4 Feb, 2016.).

Both studies met their similar primary endpoints: non-inferiority of Tresiba to Lantus in the rate of severe or blood glucose confirmed symptomatic hypoglycemia during the maintenance period (after 16 weeks of treatment).

In SWITCH 1, Tresiba also showed superiority to Lantus on the proportion of patients experiencing severe hypoglycemia during the maintenance period, a confirmatory secondary endpoint, while in SWITCH 2, the benefit did not reach statistical significance. In SWITCH 1, the proportion of patients experiencing severe hypoglycemia during the maintenance period was 10% for Tresiba versus 17% for insulin glargine.

Regulatory Supplement Targeted For Third Quarter

“We have now under rigorous blinded conditions documented the hypoglycemia benefit of Tresiba to insulin glargine both in type 1 and type 2 diabetes,” Chief Science Officer Mads Thomsen said during a same-day conference call. Novo plans to file an efficacy supplement including the SWITCH data with regulatory authorities, beginning with FDA in the third quarter, he added.

Tresiba was approved by FDA in September after a lengthy regulatory delay while the company awaited interim data from the DEVOTE cardiovascular outcomes trial, which assuaged FDA’s concerns (Also see "Novo Nordisk Plans Q1 Launch Of Long-Acting Insulin Tresiba" - Pink Sheet, 25 Sep, 2015.).

Meanwhile, Sanofi launched Toujeo last year, the same molecular entity as Lantus but in a more concentrated formula with a reduced injection volume. Sanofi has also been looking to position Toujeo as having a lower risk of hypoglycemic events versus Lantus, based on the Phase III clinical trial results, but labeling for Toujeo does not include any mention of hypoglycemic benefit versus Lantus (Also see "Sanofi’s Toujeo Is Approved, Now The Hard Part: Commercialization" - Pink Sheet, 26 Feb, 2015.).

“In our view, price aside, the collective SWITCH data places Tresiba as the class-leading basal insulin,” Deutsche Bank analyst Tim Race said in a same-day note, reaffirming estimates that the drug could surpass $2bn in sales in 2020. Nonetheless, he cautioned, “we still see differences as of minor clinical relevance to most diabetes patients and expect marketing, sales force and pricing to be critical in the changing basal insulin market.”

Pricing has become a serious issue for insulin manufacturers, who are counting on new long-acting entrants and combination products to drive growth (Also see "Market Snapshot: Under Pressure, Insulin Makers Pin Hopes On New Products" - Pink Sheet, 5 Oct, 2015.).

The pressure is only expected to intensify as follow-on versions of Lantus reach the market. Eli Lilly & Co. and partner Boehringer Ingelheim GMBH are in the lead; they already launched a copycat version branded as Abasaglar in some European countries. A similar product has been approved by FDA, but is not expected to launch until December 2016 based on a patent settlement with Sanofi (Also see "FDA Makes It Official With Basaglar Approval For Diabetes" - Pink Sheet, 16 Dec, 2015.).

More Semaglutide Data

Novo also separately announced positive top-line data from the fifth Phase III trial testing the once-weekly glucagon-like peptide-1 analog (GLP-1) semaglutide. The double-blind trial measured the efficacy and safety of 0.5 mg and 1.0 mg semaglutide compared with placebo as an add-on to basal insulin alone or in combination with metformin after 30 weeks of treatment in 397 people with type 2 diabetes.

In the study, people treated with 0.5 mg or 1.0 mg semaglutide achieved a statistically significant and superior improvement in HbA1c of 1.4% and 1.8%, respectively, from a mean baseline of HbA1c of 8.4% compared with an improvement in HbA1c of 0.1% with placebo.

A sixth trial, SUSTAIN 6, measuring cardiovascular outcomes in 3,297 patients with type 2 diabetes has not yet read out, but top-line data are expected in the first half of the year.

Novo sells the market-leading GLP-1 Victoza (liraglutide), dosed daily, but is facing increasing competition from once-weekly rivals.