Eloxx Pharmaceuticals’ cystic fibrosis candidate has failed a midphase clinical trial, dragging its battered share price down further still and leaving the future of the program in doubt.
Participants in the phase 2 study received subcutaneous ELX-02, a synthetic aminoglycoside designed to restore production of full-length functional proteins, in combination with Vertex’s Kalydeco. All of the participants had so-called nonsense mutations—a mutation in a sequence of DNA that results in a premature stop codon—putting them in the subpopulation of patients who have been left behind as treatments have improved outcomes for most people with cystic fibrosis.
After five weeks, the combination failed to significantly improve either sweat chloride concentration or percent forced expiratory volume from baseline, causing the study to miss its efficacy endpoints. Eloxx saw no incremental benefit with the Kalydeco combination.
The data drop sent Eloxx’s share price down 43% in premarket trading, sinking it to $0.22. The response of investors suggests their limited enthusiasm for the cystic fibrosis program has evaporated. However, Eloxx is yet to call time on its work on the indication.
The company claimed the results were potentially confounded by the high variability in sweat chloride and lung function measurement, adding that the variability may have resulted from low drug exposure in the lung. Steady state lung drug levels in trial participants were on average 20% of the lowest levels at which drug activity was seen in preclinical testing. The finding raises doubts about subcutaneous delivery of ELX-02.
Management will now talk to the CF Foundation, which agreed to provide Eloxx with up to $15.9 million to advance ELX-02 in March, to determine the next steps for the program. The biotech still plans to ask the FDA to begin clinical trials of an inhaled formulation of ELX-02 later this year.
Eloxx is also going ahead with a proof-of-concept trial of subcutaneous ELX-02 in patients with the kidney disease Alport syndrome, reflecting a belief the route of administration can get high levels of the drug to the targeted organ. Top-line data are due in the first half of next year, giving Eloxx a chance to generate renewed enthusiasm for its pipeline before it reaches the end of its cash runway late in 2023.