Positive Phase III data supports positioning of the human GLP-1 analog liraglutide as a once-daily injection for patients who have failed on metformin or other oral anti-diabetic drugs, Novo Nordisk said.

The Danish drug maker released top-line results June 21 from the first of five Phase III studies in its LEAD program evaluating liraglutide, demonstrating a benefit in HbA1c levels and an improvement in average weight in patients inadequately controlled by metformin and a sulfonylurea.

"I think the situation that we can confirm that will be a very strong positioning is the first once-daily offering as an injectable to patients who are failing on one, two or three OADs," Exec VP and Chief Science Officer Mads Krogsgaard Thomsen said during a same day conference call.

Pending the outcome of additional studies, liraglutide may have the potential to be used as a monotherapy following treatment with metformin or in combination with metformin alone, he indicated.

"We have done a study where we've added to metformin alone. ...We haven't seen the Phase III, and I could well imagine that a once-daily injection, if we can confirm good glycemic control, good side effect profile and weight loss, that that will be a significant element of use [for] liraglutide," he said. "Now we are moving into the Januvia territory."

Merck's dipeptidyl peptidase-4 inhibitor Januvia (sitagliptin) was approved in October as a monotherapy and as add-on therapy to metformin or thiazolidinediones to improve glucose control in patients with type 2 diabetes.

However, Thomsen admitted, "Merck has been very clever and come up with a combination called Janumet . ...You can argue that some patients will probably take Janumet before they go on to liraglutide." Janumet - a combination of Januvia and metformin - was approved in April (¹ Also see "Janumet Approved; Type 2 Diabetes Therapy Will Be Available By End Of April" - Pink Sheet, 2 April, 2007.).

The first of the Phase III studies to be released, LEAD 5, was a 26-week trial enrolling 581 patients with type 2 diabetes inadequately controlled on metformin and glimepiride. All patients in the study continued the two oral drugs and were randomized to add one daily injection of liraglutide, placebo or insulin glargine.

The average HbA1c level of patients at the beginning of the study was 8 to 8.5 percent. By the end of the treatment, more than 50 percent of those in the liraglutide group had reached the American Diabetes Association goal of HbA1c less than 7 percent. More than 35 percent reached a HbA1c target of less than or equal to 6.5 percent. The reduction in the liraglutide group was more than 0.2 percentage points better than in the insulin glargine group, a statistically significant difference.

In addition, the average weight of patients at the beginning of the study was 84 kg (187 pounds), with the average change in the liraglutide group at the end of the study being 2 kg (4.4 pounds). The difference between the liraglutide group and the insulin arm was 3.5 kg (7.7 pounds), indicating that patients in the insulin arm experienced a slight increase in weight.

Favorable weight loss could further position liraglutide competitively against Lilly/Amylin's injectable incretin mimetic Byetta (exenatide). Byetta, dosed twice daily, is approved as an adjunct for patients failing to achieve glycemic control on metformin, a sulfonylurea or a combination of the two or in patients receiving both metformin and thiazolidinediones.

However, Lilly/Amylin are also developing a once-weekly dose of Byetta, exenatide LAR, currently in Phase II, which has demonstrated weight loss of 3.8 kg (8.4 pounds) at 15 weeks in patients.

Novo expects to announce headline results from the remaining four LEAD studies during the second half of 2007 and early 2008. Those studies include evaluations of liraglutide in combination with glimepiride alone, liraglutide in combination with metformin alone, liraglutide monotherapy, liraglutide in combination with metformin and rosiglitazone.

- Jessica Merrill (j.merrill@elsevier.com)

Novo Looking To Position Liraglutide As First Once-Daily Injection Following Oral Drug Failures

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