Novo Nordisk, Emisphere Collaborate To Propel Oral GLP-1 Compounds In R&D

Emisphere carrier technology may be applied to other compounds as well.

Novo Nordisk and Cedar Knolls, N.J.-based Emisphere Technologies have entered into an exclusive agreement to develop and commercialize oral formulations of Novo Nordisk compounds, the companies announced June 23.

The agreement allows Denmark-based Novo to develop oral formulations for both its proprietary glucagon-like peptide-1 receptor agonists and other compounds using Emisphere's Eligen carrier technology. Novo will pay $87 million in product development and sales milestones to Emisphere, including $10 million in first-year payments and royalties on sales.

"We co-formulate the molecule and the carrier together," Emisphere CEO Michael Novinski told "The Pink Sheet" DAILY. "The carriers allow for improved fluidity in the gastric epithelium, allowing for availability in the blood stream through the oral route. ...You have [an orally bioavailable] molecule that is relatively unchanged from its original form."

Novinski said there is a "great deal of promise" in the GLP-1 molecules for the treatment of type 2 diabetes. "There are companies that are actively engaged in extensive research in trying to develop specific analogues," he noted.

The biggest hurdle for almost all analogues, Novinski said, is lack of oral bioavailability. "Being able to take one of these products and ... put it into the marketplace can be a game changer."

For Novo, the carrier technology represents a way to break into - and corner - the GLP-1 market. The firm submitted its once-daily injectable GLP-1 analogue liraglutide for approval as a monotherapy and add-on treatment for type 2 diabetes in the U.S. and Europe May 23 (¹ (Also see "Liraglutide Up For Approval In U.S. And Europe" - Pink Sheet, 23 May, 2008.)).

Liraglutide initially may best Amylin/Lilly's injectable incretin mimetic Byetta (exenatide), approved as an add-on therapy. Data presented at the American Diabetes Association conference in June showed significantly improved blood glucose control and slightly greater weight loss with once-daily treatment versus twice-daily Byetta (² (Also see "Roche/Ipsen Plan 2010 Filing For Once-Weekly GLP-1 Analog" - Pink Sheet, 10 Jun, 2008.)).

But Novo's pipeline will be challenged by Amylin's once-weekly formulation of Byetta, scheduled for filing during the first half of 2009, and other long-acting GLP-1 analogues in development (³ (Also see "Novo Nordisk Plans GLP-1 Analogue Expansion To Treat Diabetes, Obesity" - Pink Sheet, 31 Jan, 2008.)).

Novo pipeline targets diabetes, obesity

"We actually believe that insulin and GLP-1 are the two future exciting growth areas of diabetes, in particular type 2 therapy, and they are the ones that Novo Nordisk is focusing strongly on," Novo Chief Science Officer Mads Krogsgaard Thomsen said during a May 1 financial press briefing.

Overall efforts to expand GLP-1 to add the once-daily and once-weekly analogue for liraglutide are under way. Novo is evaluating the injectable NN9535, currently in Phase I, for once-weekly treatment for type 2 diabetes.

Novo's NN1250 and NN5401, next generation insulin analogues with improved properties, are in Phase II. The two are expected to supersede Novo's long-acting basal insulin Levemir (insulin detemir [rDNA origin] injection) and NovoMix (insulin aspart protamine/insulin aspart suspension), Thomsen noted. Novo submitted an NDA for NovoMix in December.

"We expect to report within a year on the portfolio of the second generation of our modern insulin, hopefully, being able to move those into Phase III when we get toward the end of 2009, early 2010," Chief Financial Officer Jesper Brandgaard said during the company's briefing.

Thomsen also said the company is on track to start a Phase III trial evaluating liraglutide in obese, nondiabetic patients before the end of this year. Data from Phase II will be presented at the annual Obesity Society meeting in October.

"I think the important thing is to make sure that the trial is designed so that we can file for obesity approval after the first year of study - that it's powered, that it's geared in all means and respects to achieve that target, and that the whole discussion about pre-diabetes and prevention, we're taking slightly separately of the primary endpoint, at this stage," he told analysts during the company's April 30 earnings call.

An oral fixed-combination tablet, PrandiMet (Novo's Prandin and metformin), was filed in the U.S. for type 2 diabetes treatment last August. A deal made in December allows Sciele Pharma to market Prandin (repaglinide) and PrandiMet, as well as giving it right of first refusal for U.S. marketing rights to other Novo Nordisk products containing repaglinide.

According to Thomsen, research at Novo Nordisk in Denmark will "continue to focus heavily on both injection-based delivery and alternative noninvasive routes to deliver insulin, GLP-1, as well as other therapeutic proteins within the diabetes and obesity area."

-Becky Jungbauer ([email protected])