Celtaxsys’ oral anti-inflammatory drug for cystic fibrosis, acebilustat, cleared a phase 2 study by demonstrating meaningful improvements in pulmonary exacerbations, or the acute worsening of symptoms such as heavy coughing or shortness of breath, combined with sharp decreases in lung function following irreversible organ damage.
In the 200-patient study spanning over 70 international sites, once-daily acebilustat reduced the frequency of exacerbations by 19% over 48 weeks in cystic fibrosis patients, regardless of genotype. Over 40% of treated patients did not suffer an exacerbation at all, a 32% increase compared to the placebo group, and no difference in lung function was observed.
Participants with mild lung disease—who represent about three out of four patients in the community—achieved the largest benefits, with a 34% reduction in exacerbations, Celtaxsys President and CEO Greg Duncan told FierceBiotech. Those patients also saw nearly double the likelihood, a 96% increase, of being exacerbation-free after 48 weeks in a post-hoc assessment.
“That's very important because everybody that entered our trial came in with at least one exacerbation,” Duncan said.
In addition, acebilustat-treated patients stable on therapies that modulate CFTR—the malfunctioning protein behind many cystic fibrosis symptoms—saw their exacerbation rates drop 20%, as well as a 29% increase in time to their first exacerbation and a 47% higher likelihood of having no exacerbations, when compared to patients treated with CFTR modulators and placebo alone.
“That benefit, when used in combination with a CFTR modulator, is an important consideration given the likelihood of an increase in the number of CF patients who are eligible to be treated with new CFTR modulators over the coming years,” said Steven Rowe, professor of medicine and director of the Gregory Fleming James Cystic Fibrosis Research Center at the University of Alabama at Birmingham.
“This supports the unmet need to address lung inflammation adequately for the optimal treatment of patients with cystic fibrosis,” Rowe added. The Atlanta-based Celtaxsys plans to present the trial’s full results this fall at the annual North American meeting of the Cystic Fibrosis Foundation in October, which supported the trial.
Acebilustat also showed no increased risk of infection, or immunosuppressive properties similar to corticosteroid treatments, the company said. In addition, most adverse events were mild or moderate, with a discontinuation rate in line with placebo.
Currently, Celtaxsys and its CF Foundation experts are reviewing the data, and hope to talk through phase 3 trial designs with the FDA, the EMA and potentially Australian and Canadian regulatory authorities before the end of the year, Duncan said. Celtaxsys anticipates getting underway in the second half of 2019. Acebilustat has also been granted orphan designations in the U.S. and Europe.
“If promise that we've seen in the phase 2 program holds up in a larger trial with the statistical power to see differences, acebilustat could represent a very substantial upgrade to the standard of care for patients on-or-off a modulator, and that's good news for the CF community,” Duncan said.