Melbourne-based Invion Limited, a clinical-stage drug development company focused on the development of treatments for major market opportunities in inflammatory diseases including asthma, chronic bronchitis and lupus, has just announced favorable interim results from its ongoing Phase II clinical study of INV102 (nadolol) and its efficacy in assisting patients with chronic cough, or chronic obstructive pulmonary disease (COPD) to quit smoking.

The reported interim data from this double-blind placebo-controlled randomised clinical trial comes from an analysis of sputum samples obtained from patients who have reached 1) the maximum tolerated dose of INV102, likely upon their 6th visit to a research site, and 2) four weeks of the drug’s maximum tolerated dose, likely upon their 7th visit.

The researchers noted significant changes in 4 biomarkers of inflammation in participants treated with the drug, compared to those given a placebo. The noted biomarker responses among those treated are as follows:

• IL-8, a powerful chemoattractant for inflammatory cells, was stable between visits 6 and 7, with a median decrease in IL-8 levels compared to placebo which showed a median increase in IL-8 levels;
• ERK2, a biomarker for the beta arrestin pathway, showed a greater median decrease than placebo-treated patients resulting in a lower median value at visit 7 (487 v 1,910 pg/mL);
• MUC 1, a glycoprotein that lines the surface of epithelial cells in the lung, showed a modest median decrease in patients receiving nadolol and placebo; and
• Neutrophils, the white blood cells that are the hallmark of inflammation of chronic bronchitis decreased 7% (mean) versus a mean increase of 1.4% in placebo patients.

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“These results are exciting to Invion and this field of research for three primary reasons,” said Dr. Mitchell Glass, the Executive VP of R&D and Chief Medical Officer. “First, we have clear and clinically meaningful separation between subjects treated with nadolol versus placebo in four areas of biomarker investigation. Second, the pattern of individual neutrophil changes from visit 6 to visit 7 indicates a response to nadolol treatment. Third, ERK1/2 is a hallmark of the beta arrestin pathway, the blockade of which is central to our hypothesis concerning the unique mechanism of action of nadolol. Analysis is ongoing of MUC5AC, the abnormal mucin which is specific to COPD, which will further inform us about airway healing.”

“We recognize that we must interpret these results with caution, given their interim nature, the sample size, and the variability that naturally occurs in sputum analysis. However the results support our hypothesis regarding the clinical, regulatory and commercial potential of INV102 (nadolol), and also provide a strong foundation to our inhaled INV102 program, which is approaching a major development milestone.”

These interim results were obtained from early laboratory analyses at Washington University, St. Louis, MO, USA under the supervision of Dr. Mario Castro, the smoking cessation trial’s lead researcher.