Nobex, Biocon team up on oral BNP product

RESEARCH TRIANGLE PARK, N.C.—After cementing a relationship last year to develop a novel oral insulin product, U.S. based-Nobex Corp., a drug development company specializing in oral peptide drug delivery, and Biocon Limited of India have decided to team up again. This time, they will tackle the challenge of developing an oral brain-type natriuretic peptide (BNP) product for the treatment of cardiovascular disease.  Financial terms of the agreement were not disclosed.

The goal is to advance the program to an Investigational New Drug filing with the U.S. Food and Drug Administration (FDA) and with Indian regulators in early 2007 and begin clinical trials shortly thereafter.

To reach that goal, the "usual challenges" of oral peptide drug delivery apply, notes Christopher H. Price, former Nobex president and CEO and now a consultant to the company. These include enzymatic degradation during delivery into and across the gut wall, enzymatic degradation in the blood and rapid clearance from the blood—injected BNP, for example, has a blood half-life of approximately 18 minutes.

In addition, the size of a BNP molecule is nearly five times that of the typical small molecule drug, and oral peptides tend to have less than desirable solubility in both water and lipid environments, he adds.

The fundamental  activity of BNP will not change. The oral BNP will bind to the same receptors in the circulatory system as does the infusion BNP. But pharmacokinetics and pharmacodynamics  differ.

"We predict such differences because first, we will address different indications with the oral product toward achieving significantly different clinical endpoints," he notes. "The infusion BNP can only be used in the acutely ill patient—one generally admitted to the critical care unit of a hospital with a high potential of dying. The oral BNP will be used in patients out of the hospital and on a chronic basis, probably as a single daily dose, and the blood levels will be of short duration compared with the infusion product. Also, the safety issues that have arisen with the infusion product, such as renal problems and increased mortality, are likely related to the high continuous concentrations of BNP in the critically ill patient—something we don't anticipate will be the case with the oral BNP."

Shortly after the collaboration announcement, Nobex also reported that a preclinical study involving the Mayo Clinic, using a modified human brain-type natriuretic peptide (hBNP) delivered orally, had been published in the August 9, 2005, edition of Circulation. The paper reports that a proprietary polymer-conjugated hBNP designed and developed by Nobex activates cGMP after oral delivery, resulting in increased cGMP levels in plasma and significant reductions in mean arterial pressure. Both are important biological activities associated with potential treatments for cardiovascular disease.