CF gene therapy 4D-710 wins rare pediatric disease designation

FDA’s decision follows promising data from first patients in AEROW trial

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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The U.S. Food and Drug Administration (FDA) has granted rare pediatric disease status to 4D-710, an inhaled gene therapy for people with cystic fibrosis (CF).

The designation means 4D Molecular Therapeutics (4DMT) would be eligible to receive a priority review voucher from the FDA if its gene therapy is approved. A voucher can be used in an application for a different product or can be transferred or sold to another company. The program is intended to encourage the development of therapies for serious or life-threatening rare diseases primarily affecting people age 18 and younger.

“The Rare Pediatric Disease Designation is a very important regulatory milestone in our development path for 4D-710 and highlights the urgent need for novel therapeutic options for people living with CF lung disease, including children, especially those who are not eligible for currently available disease modifying therapies,” David Kirn, MD, co-founder and CEO of 4DMT, said in a company press release.

CF is caused by mutations in the CFTR gene, resulting in no or faulty CFTR protein production. Mutations in CFTR result in thick mucus in several organs being produced.

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How does 4D-710 work in CF?

4D-710 is designed to deliver a healthy version of the gene to lung cells, called CFTRdeltaR, which was optimized to allow high production of the protein, independent of the type of mutation in the CFTR gene.

The FDA’s decision follows promising data from the first patients enrolled in the Phase 1/2 AEROW clinical trial (NCT05248230), which is testing 4D-710 in people with CF who aren’t eligible for or don’t tolerate any of the current CFTR modulators.

Among the seven patients initially enrolled, three were given the gene therapy at a dose of 1E15 vector genomes, while the other four received a higher dose — 2E15 vector genomes.

A safety analysis showed 4D-710 was well tolerated, with no clinically significant acute safety issues.

An analysis of lung tissue collected via biopsy from all the patients showed that 98% or more of the epithelial cells lining the airways had detectable CFTR protein. The levels of CFTR were at least fourfold higher than what is seen in normal lungs and about 10 times higher than what’s typical for a CF patient.

Clinically meaningful quality of life gains were seen in the three patients given the lower dose one year into treatment.

Based on these data, the next group of AEROW participants will test a lower dose of 5E14 vector genomes.

More interim data from AEROW, which is still recruiting participants at sites in the U.S., is expected by mid-year. An update about plans for a future clinical trial is expected soon, according to 4DMT.

The development of 4D-710 is supported by the CF Foundation.

“Based on the CFTR expression levels and clinical activity seen to date, we are excited about the potential for 4D-710 to transform the lives of people with CF with an effective and durable treatment option,” Kirn said.