Phase 2a clinical trial of novel CF therapy ETD001 doses first patient
Study in Europe still recruiting adults not taking CFTR modulators
The first cystic fibrosis (CF) patient has been dosed in Part A of a Phase 2 clinical trial in Europe that’s testing Enterprise Therapeutics‘ novel CF treatment candidate ETD001.
The Phase 2a trial (NCT06478706) is still recruiting adults with CF at a few sites in the U.K. and Germany, with more study centers expected to open in those countries, as well as in France. CF patients eligible for potential study enrollment are those with stable lung function who are not taking CFTR modulators, a medication used to treat the genetic condition.
“The dosing of the first person with CF in our Phase 2a trial of ETD001 represents an incredible milestone, testament to Enterprise’s dedication to advancing a novel approach to treating [people with CF] with the highest unmet medical need,” John Ford, PhD, CEO of Enterprise, said in a company press release.
“We look forward to progressing ETD001 through Phase 2 trials and beyond,” Ford added.
ETD001 aims to clear the thick mucus that’s CF’s hallmark
CF is caused by mutations that lead to no or faulty CFTR protein. This protein normally helps regulate the water content in mucus; without functional CFTR, CF patients develop thick and sticky mucus that builds up in the lungs and other organs to drive disease symptoms.
CFTR modulators are a recent class of medicines that act to boost the functionality of defective CFTR protein, and which have been found to have transformative effects. However, these modulators don’t work in patients with certain CF-causing mutations, plus some patients cannot take modulators due to side effects.
ETD001, conversely, is designed to target a different protein, called the epithelial sodium channel (ENaC), involved in mucus production. By blocking this protein’s activity, the therapy aims to increase the amount of water in mucus, thereby helping to counteract the consequences of defective CFTR and clear thick mucus.
Because it doesn’t act on the CFTR protein itself, ETD001 is expected to work similarly in CF patients regardless of their underlying mutation.
By targeting the underlying mechanisms of mucus congestion in the lungs through ENaC [protein] inhibition, ETD001 has the potential to be a transformative respiratory therapeutic.
According to Paul Russell, head of development at Enterprise, the novel therapy candidate could be a game-changer in CF.
“By targeting the underlying mechanisms of mucus congestion in the lungs through ENaC inhibition, ETD001 has the potential to be a transformative respiratory therapeutic,” Russell said.
Russell noted that ETD001’s mechanism may be beneficial not only in CF patients who can’t take modulators, but also in those with other diseases marked by a buildup of mucus in the lungs, such as asthma or chronic obstructive pulmonary disease (COPD).
Renu Gupta, MD, chief medical officer of Enterprise, said the company’s goal is to improve treatment for all CF patients.
“We are hopeful that our steadfast commitment to advancing this innovative ENaC targeting molecule, along with our partnerships with the CF community, will lead to a treatment that will vastly improve the lives of people living with CF,” Gupta said.
First part of Phase 2 clinical trial will assess therapy’s safety
The Phase 2 clinical trial testing ETD001 is taking place in two parts, the first dubbed A and the second B. In the first part, an estimated eight patients will be randomly assigned to take twice-daily ETD001 or a placebo for a week, with the main goal of evaluating the therapy’s safety profile.
In the second part of the study, 32 patients will receive ETD001 or the placebo twice daily for about a month. Participants will then undergo a month-long washout period without treatment, and then those initially given ETD001 will receive the placebo, while those first receiving the placebo will get active treatment, for another month.
The main goal of this part of the study is to assess the treatment’s impact on lung function, assessed with a standardized metric called FEV1, or forced expiratory volume in one second, which tracks how much air someone can blow out in a single forceful breath.
In an earlier Phase 1 clinical trial (NCT04926701) that tested the therapy in healthy volunteers, ETD001 was shown to be well tolerated. Additionally, a recent study in sheep indicated it was effective for clearing mucus from the lungs.
According to Ford, “ETD001 has already demonstrated an excellent safety profile in healthy participants, as well as a pharmacokinetic [how the drug moves through the body] profile consistent with a long lung residency.”
Gupta, on behalf of Enterprise, shared the company’s appreciation for everyone who helped advance ETD001 to the Phase 2 clinical trial.
“We are grateful to the [people with CF] participating in our Phase 2 study of ETD001, and to the clinical investigators for achieving this major milestone,” Gupta said.
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