Eloxx Pharmaceuticals, Inc. announced topline results from the Phase 2 clinical trial of ELX-02 in combination with ivacaftor in Class 1 cystic fibrosis (CF) patients with at least one nonsense mutation. The combination trial of ELX-02 with ivacaftor was well tolerated but did not achieve statistical significance for efficacy endpoints, including changes from baseline in sweat chloride concentration (SCC) and percent forced expiratory volume (FEV1). Topline Results of ELX-02 Phase 2 Combination Trial in Class 1 CF Patients: The Phase 2 combination clinical trial of ELX-02 was designed to evaluate safety and assess biological activity in G542X nonsense mutation Class 1 CF patients as monotherapy and in combination with ivacaftor.

The trial included a 1-week monotherapy period (1.5 mg/kg daily subcutaneous) followed by a four week combination period (1.5 mg/kg daily subcutaneous and 150 mg ivacaftor twice daily). Topline results are summarized: ELX-02 was generally well tolerated in the trial, with no treatment-related serious adverse events noted. Overall, the study did not achieve statistical significance for efficacy endpoints in the Phase 2 study in Class 1 CF for efficacy endpoints, including changes from baseline in SCC and FEV1.

No incremental improvement was observed with ivacaftor combination. Evidence of activity for ELX-02 was observed, as patients with higher baseline sweat chloride levels demonstrated increased responses as indicated by SCC (p=0.00013 at Day 35). Trial results were potentially confounded by high variability in sweat chloride and lung function measurement.

Eloxx believes this variability could have been caused by very low drug exposures in the lung. Steady state lung drug levels in patients from this trial were on average 20%, or 2µM, of the lowest levels at which drug activity has previously been seen in preclinical testing. Lung drug exposure with inhaled delivery of ELX-02 expected to be at least 50-fold greater than with subcutaneous delivery.