KaloBios Pharmaceuticals reported data from its phase I/II study in persistent asthma for KB002 (precursor chimeric anti-GM-CSF monoclonal antibody to KB003).
The findings demonstrated preliminary safety, tolerability and signs of activity of anti-GM-CSF antibodies in asthma and support continued development of the company's Humaneered KB003 anti-GM-CSF monoclonal antibody in severe asthma. KB003 is currently in a phase II trial in severe asthma patients inadequately controlled by corticosteroids.
"These initial clinical results with KB002 in asthma are highly encouraging," said Nestor Molfino, chief medical officer, KaloBios. "KB002 was well-tolerated, with no significant adverse events in the study population. When KB002 was added to patients' standard of care treatment, the study also showed a reduction in airway inflammation and improvements in FEV(1), a measure of lung function. Moreover, asthmatics with reversible FEV(1) at baseline showed greater FEV(1 ) responses than non-reversible patients. As a result, we are targeting this patient population in our ongoing phase II KB003 study."
The KB002 phase I/II asthma study randomized 24 subjects to receive either KB002 or placebo. The objectives of the study primarily were to evaluate safety and tolerability, effects on sputum inflammatory markers, and lung function after a single dose of KB002. KB002 was found to be generally safe and well tolerated. Mean FEV(1) value for the active treatment group increased 120ml from baseline to day 42 and decreased 40ml for the placebo group. Of the 24 subjects enrolled (17 on KB002 and seven on placebo), 59% on KB002 versus 29% on placebo had a >100ml FEV(1) increase at day 42.
In addition, when patients were segmented retrospectively by the criteria of "reversibility," with reversible patients defined as having a >12% improvement in FEV(1) from baseline after a beta agonist, reversible patients on KB002 experienced a greater increase in FEV(1) from baseline at day 42 versus those on placebo. A majority of responders showed an FEV(1) improvement of more than 10%, which is a level that is generally accepted as clinically meaningful. At day 42, 78% of KB002-treated reversible subjects had at least a 100-mL increase in FEV(1) compared with 38% of KB002-treated nonreversible subjects, 33% of placebo-treated reversible subjects and 25% of placebo-treated nonreversible subjects. A majority of KB002-treated patients who had an improvement in FEV(1) also had measureable antibody in the sputum in addition to a decrease in eosinophils or neutrophils at day 28.