- Private biotech Celtaxsys announced Thursday its lead candidate failed to hit a mid-stage study's primary endpoint of improved lung function in cystic fibrosis patients.
- Treatment with acebilustat, a small molecule drug that inhibits an enzyme involved with inflammation, was no different than placebo at increasing from baseline a measure of lung function called forced expiratory volume in one second percent predicted (FEV1pp).
- In announcing the data, Celtaxsys focused on the "clinically meaningful" benefit its drug appeared to have on pulmonary exacerbations (PEx) — one of the study's secondary endpoints. Compared to placebo, patients taking acebilustat experienced 19% fewer PEx and a 22% reduced risk of having their first PEx.
Smaller biotechs in the CF space are having a hard time keeping up with Vertex Pharmaceuticals and its growing portfolio of drugs. Earlier this year, regulators approved the company's third CF product, Symdeko (tezacaftor/ivacaftor), another therapy aimed at modifying the cystic fibrosis transmembrane conductance regulator (CFTR), a protein at the core of the disease.
The approval of Symdeko and other Vertex drugs hinged on data showing they improved lung function, arguably the most important treatment effect for people with CF. Celtaxsys was looking to see whether its candidate could also offer a benefit there, but topline results from the Phase 2 EMPIRE-CF trial aren't boding well.
Not only did acebilustat fail to outperform placebo in FEV1pp, but the FEV1pp response didn't correlate with PEx rates, according to Celtaxsys. Still, the biotech sees promise in the drug's effect on PEx — particularly for patients with less severe lung function impairment.
"The large clinically meaningful differences we see with acebilustat treatment as compared to placebo in both frequency of pulmonary exacerbations and time to first pulmonary exacerbation, especially in the mild patient population who exhibited a 34% reduced rate of exacerbations and a 43% reduced risk of progression to their first exacerbation versus placebo, are very promising and will inform us as we prepare for our Phase 3 trials," a Celtaxsys spokesperson wrote in an email to BioPharma Dive.
"Reduction in pulmonary exacerbations is also significant from a health economics perspective, as reducing pulmonary exacerbations will reduce the amount of time patients need to spend in the hospital and the amount of antibiotics they require," the spokesperson added.
The company also highlighted findings from patients who received both acebilustat and CFTR modulators. Those patients showed a 20% reduction in PEx, had 29% more time before their first exacerbation and were 47% more likely to have no exacerbations compared to patients treated with CFTR modulators and placebo.
Further testing is needed to support the optimism, however, as EMPIRE-CF wasn't powered to show a statistical difference on PEx.
EMPIRE-CF enrolled 200 CF patients regardless of genotype. On safety, the trial found acebilustat was well-tolerated and didn't lead to increased risk of infection. Most of the adverse events were mild or moderate, with the most common across experimental and control groups being infective PEx, cough, nasopharyngitis and several others.