ELX-02 is an experimental treatment being developed by Eloxx Pharmaceuticals to treat cystic fibrosis (CF) caused by nonsense mutations.

How ELX-02 works

CF is a heritable disease caused by mutations in the CFTR gene, which results in the CFTR protein being made incorrectly or not at all. The protein functions as a channel at the cell membrane to allow salts to travel in and out of cells. The absence or malfunction of the protein leads to insufficient salt being transported across cell membranes, which causes a buildup of sticky mucus in organs, interfering with their function. The most common mutation in the CFTR gene is called the F508del mutation, which causes the CFTR protein to misfold.

ELX-02 targets a less common mutation known as a nonsense mutation where there is a premature stop signal in the CFTR gene. This premature stop signal causes the cellular machinery to stop making the CFTR protein midway. The resulting incomplete protein is quickly degraded by the cell.

The treatment binds to ribosomes, proteins in the cell responsible for synthesizing other proteins, and changes how it reads the instructions of the CFTR genetic template. It’s designed to increase the read-through of nonsense mutations, in essence telling the ribosome to skip over the stop signal. In this way, ELX-02 helps ensure that sufficient quantities of full-length CFTR protein are made in order to lessen the burden of CF.

ELX-02 in clinical trials

A Phase 1 clinical trial (NCT03292302) to assess the safety, tolerability, and pharmacokinetics (movement in the body) of ELX-02 in healthy volunteers has been completed. A total of 18 healthy volunteers were randomly assigned to receive a single subcutaneous, under the skin, dose of ELX-02 or a placebo. Participants were assessed before treatment and 10 days after.

The results were published in the journal Clinical Pharmacology in Drug Development and showed that 62.5 percent of participants experienced at least one side effect following treatment with ELX-02. However, 45 percent of participants also experienced at least one side effect following treatment with a placebo. All of the side effects reported were mild. Medications that work like ELX-02 have been known to cause damage to kidneys or hearing, so this was assessed in the trial. No toxicity in either area was reported for volunteers treated with ELX-02.

Another Phase 1 clinical trial (NCT03309605) recruited 62 healthy adults in Belgium to further assess the safety, tolerability, and pharmacokinetics of ELX-02. Of the 62 participants, 55 completed the study and were randomized to receive ELX-02 or a placebo twice a week for 29 days. The participants were also randomized to one of seven cohorts that would each receive ascending doses of ELX-02 ranging from 0.1 mg/kg to 5.0 mg/kg.

The results of the study were published in the journal Clinical Pharmacology in Drug Development and showed that the levels of ELX-02 in the blood increased as the dose increased and did not appear to accumulate in the body. The adverse events reported were mostly related to reactions at the site of the injection. One of the treatment participants and two of the placebo participants in the highest dose cohort did experience declines in their hearing thresholds. The declines had either cleared up or were moving toward returning to normal after the treatment was stopped. The results of the study supported further investigation into ELX-02 in Phase 2 trials.

ELX-02 is currently being investigated in two Phase 2 clinical trials in patients with CF. Both trials are open-label where the patients know that they are receiving the treatment. On trial, called EL-004 (NCT04126473), is currently recruiting patients in Israel or Germany while the other, called EL-012 (NCT04135495) is recruiting patients at one of seven locations in the U.S. To be enrolled in either trial, patients must have at least one copy of the G542X allele, the most common type of missense mutation in CF patients. EL-004 is recruiting up to 16 patients and EL-012 is recruiting 8. In both studies, at least four participants must have two copies of the G542X allele and the rest of the participants can have one G542X allele and the second mutation can be any Class 1 or Class 2 mutations besides F508del. In the trials, patients will receive ascending doses of ELX-02 at each administration starting at a dose of 0.3 mg/kg per day and increasing to 0.75, 1.5, and finally 3 mg/kg per day.

Both studies were close to completing enrollment in January of 2020 but were paused in March due to concerns of COVID-19 infections. Both studies have resumed recruitment now, however. Patients in the study will be monitored for any adverse reactions to treatment. The concentrations of sweat chloride and measurements of lung function will also be recorded periodically during the study. Both studies are expected to conclude in June 2021.

Other information

ELX-02 received orphan drug designation from the European Medicines Agency (EMA) in December 2018 and from the U.S. Food and Drug Administration (FDA) in August 2020.


Last updated: Feb. 23, 2021


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