Inhaled CF treatment shows promise for patients not taking CFTR modulators
Enterprise's ETD001 shown to improve lung function in small clinical trial
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ETD001, an inhaled therapy for cystic fibrosis (CF), appeared to work better than a placebo at improving lung function in CF patients not taking CFTR modulators — approved therapies that only work in people with certain CF-causing gene mutations — in a small clinical trial.
That’s according to results announced by the therapy’s developer Enterprise Therapeutics, which noted that ETD001 is “designed to treat the 10% of people with [CF] with the highest unmet medical need.”
Overall, the trial data showed the inhalation therapy was safe and well tolerated, Enterprise stated in a company press release.
“We are delighted to report positive results from this Phase 2 trial of ETD001. These data demonstrate that this novel [therapy] is well tolerated in [people with] CF, and has shown improvement in lung function over a 28 day period compared to [a] placebo,” said Renu Gupta, MD, Enterprise’s chief medical officer.
Gupta added: “We are encouraged by the potential of ETD001 to be a novel therapeutic option for improving the lives of all [people with] CF, particularly those currently without effective therapies, and we are grateful to everyone who took part in this trial.”
CF is caused by mutations in the gene that encodes CFTR, a protein that helps regulate the movement of water and ions, or salt molecules, in and out of cells. Lacking functional CFTR, people with CF produce unusually thick and sticky mucus, which builds up in the lungs and other organs to drive disease symptoms.
CFTR modulators are a class of medicines that can boost the functionality of defective CFTR protein, but they only work for certain patients. Additionally, some people who have eligible mutations can’t take these therapies due to side effects.
New inhalation treatment designed for ‘all people with CF’
ETD001 is designed differently — to target a protein known as ENaC, short for epithelial sodium channel. Like CFTR, ENaC normally helps control the movement of water and salt molecules in and out of cells, though ENaC specifically moves sodium ions instead of chloride ions. Sodium and chloride are best known as the two components of table salt.
By blocking the activity of ENaC, ETD001 aims to normalize the amount of water in mucus regardless of the type of mutation a person has. In a study involving healthy volunteers, the therapy was shown to be tolerated well.
These new data come from a Phase 2 trial (NCT06478706), sponsored by Enterprise, that enrolled 57 people with CF who were not taking CFTR modulators. In the first part of the study, patients were given ETD001 for a week to monitor for safety outcomes. According to the developer, the treatment overall was well tolerated, with a safety profile consistent with what’s expected for people with CF receiving an inhaled therapy. The company did not provide further details.
The second part of the study tested ETD001 against the placebo. For about a month, some patients were assigned to twice-daily treatment with ETD001, while others received the placebo. Then, after a four-week washout period, patients initially given the placebo were given ETD001 for a month and vice versa. A washout period allows a tested treatment to fully leave the body.
The main goal of this part of the study was to assess the impact of treatment on a standard measure of lung function called forced expiratory volume in one second, or FEV1. The results showed that use of ETD001 led to a statistically significant improvement in FEV1 relative to the placebo, by 3.4% on average.
We are excited by the potential that these data offer for enhancing treatment options for all [people with] CF. … To observe lung function improvement within 28 days of treatment with ETD001 is a significant milestone and we are now looking forward to progressing into longer duration clinical trials, where we expect to see further clinical benefit.
Martin Gosling, PhD, Enterprise’s chief scientific officer, noted that this study marks the first positive results for a therapy targeting ENaC in a CF clinical trial.
“We are excited by the potential that these data offer for enhancing treatment options for all [people with] CF. … To observe lung function improvement within 28 days of treatment with ETD001 is a significant milestone and we are now looking forward to progressing into longer duration clinical trials, where we expect to see further clinical benefit,” Gosling said.
Enterprise said it will present in-depth results from the Phase 2 study next month at the European Cystic Fibrosis Society conference in Lisbon, Portugal. The company is also planning to launch additional Phase 2 studies to test different doses of ETD001 for a longer period in CF patients. Testing ETD001 given along CFTR modulators is also planned.
John Ford, PhD, Enterprise’s CEO, offered thanks to “everyone involved in developing the ETD001 program to this stage,” adding that “it’s really heartening to see the results from this Phase 2 trial.”
Ford said the company is “now looking forward to developing this candidate further, and being one step closer to improving outcomes for people living with respiratory disease.”
