E!6628 Alginate derived oligosaccharide G-block as a new drug candidate in the treatment of cystic fibrosis

OligoG er et nytt inhalerbart legemiddel basert på alginat, som utvikles for behandling av cystisk fibrose (CF). Prosjektets mål var å gjennomføre kliniske studier i fase 2 som viser OligoG's effekt i pasienter. I løpet av prosjektperioden har det blitt gjennomført en klinisk studie som viste hvordan legemiddelet fordeler seg i pasientlunger, ved å benytte radioaktivt merket legemiddel. Studien viste at OligoG tørt pulver for inhalasjon som har blitt utviklet i prosjektet, gjør at vesentlig mer OligoG når lungene i CF pasienter enn OligoG løsning for nebulisering, som tidligere har blitt benyttet i fase 1 og 2a. Klinisk fase 2 effektstudier er initiert, og vil blir ferdigstilt etter at Eurostars-prosjektet formelt er avsluttet.

BACKGROUND Cystic fibrosis (CF) is a disease in which pulmonary function is compromised by elevated mucus viscosity, secondary to a defect in the Cystic Fibrosis Transmembrane Regulator (CFTR) protein. The elevated viscosity is associated with mucin polym er cross-linking. Chronic pulmonary colonization of Pseudomonas spp. represents a significant clinical problem in CF patients, especially as the mucoid phenotype expresses biofilm which again acts as a protective layer for the bacteria. One innovative app roach towards developing new drugs for this condition would thus be to design a drug which promotes sputum clearance whilst also increasing the effectiveness of current antibiotics in situ. Model systems and ex vivo studies on CF sputum indicate that Olig oG indeed: (1) reduces CF sputum viscosity and weakens microbial biofilms via inhibition of polymeric cross-linking (this may increase pulmonary clearance of sputum, and may promote diffusion of antimicrobial agents into microbial biofilms and augment the ir effectiveness); and (2) shows antimicrobial properties through intrinsic antimicrobial effects of OligoG, and through reduction in MICs for selected antibiotics. This project is comprised of 3 separate work packages: WP1 Consortium Administration and Management, WP2 A pharmaco-scintigraphic study to measure lung deposition and pharmacokinetics and WP3 A phase IIb clinical dose-response trial. In WP2 a present inhalation formulation (6% OligoG solution nebulized) will be compared to a dry powder formul ation developed in the project. The aim of this study will be to generate in vivo deposition data using gamma scintigraphy. The project further aims to run a clinical proof of concept study (phase 2B-study) WP3.