Phase 3 trial for CF gene therapy 4D-710 planned for late 2025

Results of trial could be basis of applications seeking approval of therapy

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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4D Molecular Therapeutics (4DMT) is planning a Phase 3 clinical trial that, if results are positive, will be the basis of applications seeking approval of the company’s inhaled gene therapy 4D-710 as a treatment for people with cystic fibrosis (CF) who can’t take CFTR modulators.

4DMT recently completed discussions with regulatory authorities in the U.S. and Europe, and the company says it now sees a clear path for how to get the therapy formally approved.

“We are encouraged by our productive interactions with the [U.S. Food and Drug Administration] and [European Medicines Agency] on pivotal development plans for 4D-710, which we believe has the potential to be a transformative therapy for people with the highest unmet medical need for CF lung disease,” David Kirn, MD, co-founder and CEO of 4DMT, said in a company press release.

The planned Phase 3 trial is expected to enroll 60 to 80 people with CF who have reduced lung function, specifically a percent predicted forced expiratory volume in one second (ppFEV1) score of 40% to 80%. One of the study’s main goals will be to measure how treatment with 4D-710 affects ppFEV1, which is a measure of lung function based on how much air someone can forcibly exhale in one second.

The Phase 3 study also will assess how the gene therapy affects patients’ quality of life — measured with a standard scale called the Cystic Fibrosis Questionnaire Revised Respiratory Domain (CFQ-R-RD) — and the frequency of lung exacerbations (when lung function suddenly worsens).

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Manufacturing facilities set up to make CF gene therapy for trial

The trial is expected to launch in the second half of 2025. 4DMT said it has already set up manufacturing facilities to make the gene therapy for the trial following the same procedures that could be used to make commercial product if it’s ultimately approved.

“We are committed to advancing 4D-710 into pivotal trial development efficiently,” said Kirn, noting that 4DMT is currently focusing resources on finishing Phase 3 clinical development of another experimental gene therapy that’s designed to treat an eye disorder called neovascular age-related macular degeneration (also known as wet AMD).

CF is caused by mutations in the gene CFTR, which provides instructions for making a protein with the same name. Without functional CFTR protein, the body produces abnormally thick and sticky mucus, which builds up in organs and drives most disease symptoms.

In recent years, a new class of therapies called CFTR modulators has transformed the treatment landscape for most patients. CFTR modulators can boost the functionality of the mutated protein in eligible patients, but some disease-causing mutations don’t respond to these medicines.

4D-710, which recently scored FDA rare pediatric disease designation, is designed to deliver a healthy copy of the CFTR gene to lung cells, allowing production of a functional CFTR protein. 4DMT is developing the gene therapy for people with CF who can’t take CFTR modulators, either because they don’t have eligible mutations or because modulators were causing intolerable side effects.

Since there’s a major unmet need for treatments in these patients, 4DMT said it is exploring the possibility of seeking accelerated approval for 4D-710. Accelerated approval is a conditional approval that lets companies market a therapy based on promising early clinical data, with the requirement that the company still conduct further tests to prove the therapy is effective.

4DMT is currently running a Phase 1/2 clinical trial called AEROW (NCT05248230) testing 4D-710 in CF patients who can’t take modulators. Biopsy data from the first seven patients, treated at one of two doses, showed the therapy led to CFTR protein levels higher than what’s typically seen in people who don’t have CF, with no serious safety issues reported.

So far a total of nine patients have been treated with 4D-710 at four different dose levels in the AEROW trial, according to 4DMT. The company is planning to present interim data from all these patients, as well as updates on the development of 4D-710 and a plan for CF patients who are on modulator therapy, at the 47th European Cystic Fibrosis Conference in June.