KB407 Earns Orphan Drug Status in Europe
The potential gene therapy already has that designation in the US
The European Commission (EC) has granted orphan drug designation to KB407, Krystal Biotech’s potential inhaled gene therapy for cystic fibrosis (CF).
Orphan drug status is intended to encourage the development of therapies for rare, life-threatening, or chronically debilitating conditions, through a series of benefits, such as 10 years of market exclusivity after approval. The U.S. Food and Drug Administration (FDA) granted KB407 a similar designation in 2020.
“We are pleased that the European Commission has granted orphan drug designation to KB407, which we believe is an important step toward advancing this option to treat patients with CF,” Suma Krishnan, president of research and development at Krystal, said in a press release.
CF is caused by mutations in the CFTR gene, resulting in a CFTR protein with the wrong shape or in complete lack of this protein. CFTR normally controls the flow of water and chloride ions into and out of cells, but when the CFTR gene is mutated it leads to the excessive production of thick mucus in several organs, such as the lungs.
KB407 is a repeat-dose CF gene therapy that uses a modified version of the herpes simplex virus 1 (HSV-1) to deliver two healthy copies of the CFTR gene to airway cells. The therapy aims to restore ion and water flow into and out of lung cells, regardless of the type of CFTR mutation carried by patients (More than 2,000 mutations have been described.)
In studies in animals, KB407 was delivered successfully to the lungs by inhalation with the help of a nebulizer. Also, it promoted the production of normal CFTR protein in lung cells, as well as in patient-derived organoids — 3D “mini-organs” that better mimic diseased tissue.
In August 2022, the FDA cleared a Phase 1 clinical trial (NCT05504837) that seeks to assess the safety and tolerability of ascending doses of KB407, administered via a nebulizer, in 20 adults with CF. The trial’s completion is due by March 2024.
Treatment effects on lung function, assessed by measuring forced expiratory volume in one second (FEV1), or how much air someone can forcibly exhale in a second, also will be investigated. More information is available here.
Another Phase 1 trial (NCT05095246), underway at a single site in Australia, also is testing ascending doses of KB407 in up to 13 adults with clinically stable CF. The trial is currently recruiting patients and is due to conclude in October 2024.