Once-Weekly Insulin Added To Novo Nordisk’s Clinical Pipeline

Novo Nordisk is evaluating new long-acting and quick-acting insulins in clinical trials as competitive pressure looks set to intensify in 2013 for its market-leading GLP-1 agonist, Victoza.

A potential once-weekly insulin analog, LAI287, is among a number of investigational therapies for type 1 and type 2 diabetes being evaluated by Novo Nordisk AS.

A Phase I clinical trial with LAI287 has started in 80 patients with type 1 diabetes, reported Novo Nordisk's Chief Scientific Officer Mads Krogsgaard Thomsen during the company's financial results call Jan. 31. The aminoacid backbone and fatty acid side-chains of insulin have been changed to extend its circulating half-life, with the stability of the resulting molecule also likely allowing oral dosing, Thomsen said.

Novo Nordisk is also looking at the other end of the pharmacokinetics spectrum with a faster-acting formulation of the company's marketed short-acting insulin NovoLog/NovoRapid (aspart) also in clinical studies. The aim is to better mimic the insulin secretory response of healthy individuals.

Natural excipients have been used to develop a new insulin formulation that acts within minutes, Thomsen reported. In Phase I studies, the new formulation, FIAsp, had a quicker onset of action than NovoLog with a similar duration, and a Phase III program, called “Onset”, in 3,000 patients with type 1 and 2 diabetes, is due to start by the end of 2013. The studies will evaluate multiple injections and infusions to find the optimal dosing regimen, Thomsen said.

Victoza In Type 1 Diabetes

Another Phase IIIA program, ADJUNCT, is due to start in the second half of 2013 to assess adding Novo's marketed GLP-1 agonist, liraglutide (Victoza) to the insulin therapy of patients with type 1 diabetes.

"Type 1 diabetics are taking multiple insulin injections, and the aim of ADJUNCT is to evaluate a new treatment paradigm, whereby liraglutide would reduce excess glucagon and thereby the insulin requirement, reduce body weight so that patients become more insulin sensitive, and reduce the number of hypoglycemic episodes," Thomsen said.

FDA and EMA have just recently cleared two major clinical studies, the first a one-year study and the second a six-month study, to start later this year, he added.

Nearer the market is IDEgLira, a fixed-dose combination of liraglutide and Novo Nordisk's new long-acting insulin, Tresiba (insulin degludec), for use in type 2 diabetes. IDEgLira is expected to be submitted for approval in the EU in mid-2013, and in the U.S. in 2013 after Tresiba's gains an approval there (Also see "Beyond Victoza: Novo Nordisk Sheds Light On GLP-1/Insulin Product" - Pink Sheet, 13 Aug, 2012.).

Thomsen presented headline data from the second Phase IIIA study of IDegLira in type 2 diabetes (DUAL II), showing that uses of the combination reduced mean HbA1c to 6.8%, a statistically significant decline from a mean baseline HbA1c of 8.7%. Body weight also declined by a statistically significant 2.5kg on average.

Liraglutide is also in a Phase III trial in patients with severe obesity, to evaluate its use along with lifestyle changes, including diet, to produce sustainable weight loss, particularly in patients at risk of developing diabetes (Also see "Novo Plans Phase III Program To Pick Up Obesity Claim For Victoza" - Pink Sheet, 22 Jun, 2010.).

Novo Nordisk president and CEO Lars Sorensen said obesity could represent a significant opportunity for the company, as the number of individuals with obesity is similar to the number of diabetics.

Victoza Drives Growth

Novo Nordisk’s sales grew by 12% in local currencies during 2012 to reach DKK 78 billion ($14 billion), driven by sales of Victoza, which grew by 50% to DKK 9.5 billion, and its insulin products NovoLog/NovoRapid and Levemir (insulin detemir). Victoza is Novo Nordisk’s fastest growing product, but its sales growth is likely to come under increasing pressure from competing glucagon-like peptide-1 (GLP-1) agonists launched by other companies over the coming months, and the revitalization of the marketing of Amylin Pharmaceuticals’ GLP-1 agonists.

Victoza now has 62% of the GLP-1 receptor agonist market in the U.S. by value, and in 2012 its sales were "unaffected by competitor products, although a slightly lower growth rate is expected in 2013 as competitive pressures intensify," Sorensen said.

There are a number of GLP-1 agonists nearing the market. Sanofi and Zealand Pharma AS's GLP-1 agonist, Lyxumia (lixisenatide), received a positive opinion from Europe's CHMP in November 2012 (Also see "GLP1 Diabetes Showdown Nears As Lyxumia Gets Green Light In Europe" - Pink Sheet, 16 Nov, 2012.). GlaxoSmithKline PLC submitted its once-weekly GLP-1 agonist, albiglutide, for U.S. FDA review in Jan.2013 (Also see "GSK Highlights Easy Pen Delivery Of Albiglutide As FDA Begins Review" - Pink Sheet, 14 Jan, 2013.). And Amylin's marketed GLP-1 agonist, Bydureon (extended release exenatide) is likely to get a boost following the acquisition of the company jointly by AstraZeneca PLC and Bristol-Myers Squibb Co. (Also see "$7 Billion Amylin Buyout Boosts BMS, AZ Diabetes Partnership" - Pink Sheet, 30 Jun, 2012.).

North America was the major contributor to Novo Nordisk’s sales growth during 2012, with the company’s sales growing by 19% in the region, compared with a growth rate of 2% in Europe and 16% in International markets.

In 2013, Novo Nordisk expects total sales to grow by 8-11% in local currencies, with the growth rate 4.5% lower in Danish krone because of negative foreign exchange trends - 2013 sales will be driven by a steady increase in Victoza sales and positive contributions from Tresiba, which was approved in the EU in January following a positive opinion in October 2012, Sorensen said (Also see "EU Insulin Battle Looms After EMA Panel Backs Novo’s Insulin Degludec" - Pink Sheet, 19 Oct, 2012.). Tresiba is expected to be launched in Denmark and the U.K. in the first quarter of this year. It is awaiting approval in the U.S. Operating profit is forecast to grew by 10% in local currencies, and 7% lower in local currencies.