The combination of the small molecule ELX-02 and ivacaftor (Kalydeco®) was well tolerated by cystic fibrosis (CF) patients with class I mutations, but failed to achieve efficacy endpoints of a phase 2 trial. Efficacy endpoints included changes from baseline in sweat chloride concentration and percent forced expiratory volume.

“We are disappointed that ELX-02 failed to achieve statistical significance for its key efficacy endpoints in this phase 2 trial in combination with ivacaftor for the treatment of class I CF,” said Sumit Aggarwal, president and chief executive officer of Eloxx Pharmaceuticals. the developers of ELX-02.

“Despite this setback, we were pleased to observe that ELX-02 was well tolerated and demonstrated additional evidence of activity in this underserved patient population.”

Despite the lack of statistical significance for efficacy endpoints, researchers did find evidence of ELX-02 activity. They hypothesized that results could have been potentially confounded by high variability in sweat chloride and lung function measurement due to very low drug exposures in the lung.

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The trial aimed to evaluate the safety and efficacy of ELX-02 as monotherapy and in combination with ivacaftor in class I CF patients with a G542X nonsense mutation. The protocol included subcutaneous administration of ELX-02 (1.5 mg/kg daily) for 1 week followed by a 4-week combination period (1.5 mg/kg daily subcutaneous and 150 mg ivacaftor twice daily).

Steady-state lung drug concentration achieved with this protocol was on average a fifth of the lowest levels at which drug activity was reported in preclinical testing. The research team expects to be able to increase lung drug exposure at least 50-fold using an inhaled formulation of ELX-02.

“We will work closely with the CF Foundation, as it has generously supported this trial, to determine the next steps in the development of ELX-02 for CF,” Aggarwal said.


Eloxx Pharmaceuticals reports topline results from phase 2 combination clinical trial of ELX-02 in class 1 cystic fibrosis (CF) patients. News release. Eloxx Pharmaceuticals, Inc; September 14, 2022.