NEW YORK – Krystal Biotech on Thursday said it has gained permission from the US Food and Drug Administration to begin clinical trials to evaluate the safety and efficacy of KB408, its gene therapy candidate for the rare, inherited disease alpha-1 antitrypsin deficiency (AATD).
Pittsburgh-based Krystal in August submitted an investigational new drug (IND) application to the FDA to request permission to start a Phase I trial of KB408, a gene therapy that delivers two full-length copies of SERPINA1 — the gene perturbed in AATD. It's delivered with an HSV-1-derived vector designed to enable expression of the alpha-1 antitrypsin protein.
The gene therapy is formulated to be used with a nebulizer, so that patients inhale the medication, which is delivered to respiratory cells in the lungs.
Krystal expects to dose the first patient in the open-label Serpentine-1 trial in the first quarter of next year, with three planned dose levels of three patients each. Adults with AATD and a Pi*ZZ genotype, meaning two copies of the Pi*Z allele, will be eligible to enroll. Homozygous carriers of this allele have the most severe form of the disease, which causes progressive enzymatic destruction of lung tissue, ultimately causing life-threatening pulmonary impairment and severe respiratory insufficiency.
"This IND acceptance represents an important milestone for us as we work to address a serious lung disease with limited treatment options and also allows us to demonstrate the potential of our platform to deliver genes repeatedly to epithelial cells of the lung," Hubert Chen, senior VP of clinical development at Krystal, said in a statement.
The FDA also has granted orphan drug designation to KB408, according to Krystal.