RARE Daily

FDA Grants Rare Pediatric Disease Designation to 4DMT for Aerosolized Treatment of Cystic Fibrosis

January 23, 2024

Rare Daily Staff

The U.S. Food and Drug Administration granted Rare Pediatric Disease designation to 4D Molecular Therapeutics for its aerosolized 4D-710 for treatment of cystic fibrosis lung disease.

Cystic fibrosis (CF) is an inherited, progressive disease caused by mutations in the CFTR gene. It affects the lungs, pancreas, and other organs. According to the CF Foundation, nearly 40,000 people in the United States and more than 105,000 people worldwide are living with cystic fibrosis, with approximately 1,000 new cases of cystic fibrosis diagnosed in the United States each year. Lung disease is the leading cause of morbidity and mortality in people with cystic fibrosis. Cystic fibrosis causes impaired lung function, inflammation and bronchiectasis and is commonly associated with persistent lung infections and repeated exacerbations due to the inability to clear thickened mucus from the lungs. People with cystic fibrosis require lifelong treatment with multiple daily medications. The complications of the disease result in progressive loss of lung function, increasing need for IV antibiotics and hospitalizations, ultimately leading to end-stage respiratory failure.

4D-710 is comprised of a targeted next generation vector and a codon-optimized CFTR∆R transgene. 4D-710 has the potential to treat a broad range of people with cystic fibrosis, independent of the specific CFTR mutation, and is designed for aerosol delivery to achieve CFTR expression within lung airway epithelial cells. 4D-710 is being initially developed for the approximately 15 percent of people whose disease is not amenable to existing CFTR modulator medicines targeting the CFTR protein.

4D-710 is currently being evaluated in the phase 1/2 AEROW clinical trial in people with cystic fibrosis who are not eligible for, or cannot tolerate any of, the currently approved CFTR modulators. 4D-710 has demonstrated promising, reproducible, CFTR expression significantly above normal levels for seven patients across Cohorts 1 and 2 (1E15-2E15 vg) and durable improvement or stabilization of quality of life and pulmonary function for three patients through 12 months in Cohort 1. Given above normal CFTR transgene expression (~400 percent of normal lung levels), dose exploration continues with evaluation of lower doses (Cohort 3 dose 5E14 vg). Interim data update from phase 1/2 AEROW clinical trial is expected in mid-2024.

The FDA grants Rare Pediatric Disease designation to incentivize development of new treatments for serious or life-threatening diseases that primarily affect children ages 18 years or younger with fewer than 200,000 people affected in the United States. The RPDD program allows for a sponsor who receives an approval to qualify for a priority review voucher (PRV) that can be deemed to receive an expedited six-month priority review for any subsequent marketing application or may be sold or transferred. Most recently, Sarepta Therapeutics sold a PRV for $102 million.

“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,” said David Kirn, co-founder and CEO of 4DMT. “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.

Photo: David Kirn, co-founder and CEO of 4DMT

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