NOBEX and Biocon to Codevelop Oral Peptide for Treating Congestive Heart Failure
NOBEX Corp. (Research Triangle Park, NC) and Biocon Ltd. (Bangalore, India) will codevelop an oral formulation of human brain-type natriuretic peptide (hBNP) for the treatment of congestive heart failure. The program combines Biocon’s peptide production capabilities with Nobex's peptide delivery technology.
The companies anticipate an investigational new drug application filing with the US Food and Drug Administration and with India's regulatory agencies in early 2007, with clinical trials beginning later that year.
The oral formulation of conjugated hBNP applies Nobex’s proprietary amphiphilic oligomer technology to the hBNP endogenous peptide produced in the heart, and is known for its natriuretic, diuretic, vasorelaxant, and lusitropic properties. In 2001, FDA approved hBNP for administration as a continuous infusion in hospital settings (currently marketed by Scios, Inc., a Johnson & Johnson Company). Nobex and Biocon researchers hope an oral formulation of the drug will extend hBNP administration to outpatient use in subjects with early asymptomatic left ventricular dysfunction, as well as patients at high risk of acute decompensation of heart failure.
At the AAPS Biotech conference held earlier this year, NOBEX researchers presented experimental results showing how BNP conjugates could be produced by coupling monodispersed low molecular weight (typically less than 500 Da) amphiphilic oligomers to the BNP therapeutic peptide. An amphiphilic structure has both a highly water-soluble end and a highly lipid-soluble end. The balance between the water-soluble and the lipid-soluble portions modify the chemical and biological properties of the drug to improve its characteristics and enable oral delivery. The study claims the conjugated peptides lead to increased shelf stability, a greater resistance to enzymes, better absorption into the body from the gastrointestinal tract, and longer circulation time in the body.
Another study published earlier this month (A. Cataliotti et al., “Oral Human Brain Natriuretic Peptide Activates Cyclic Guanosine 3',5'-Monophosphate and Decreases Mean Arterial Pressure,” Circulation112, 836–840 ) reported for the first time that “the Nobex-modifled hBNP had a significant reduction in mean arterial pressure and increased blood levels of a second messenger called cyclic GMP in an animal model. The study also showed the activity of the hBNP is maintained and its oral bioavailability is several times greater than the unmodified natural peptide at the same oral dose and the same liquid formulation.”