Orphan Drug Designation Granted to KB105 for the Treatment of TGM-1 Deficient ARCI

This morning, August 9, 2018, the US Food and Drug Administration (FDA) granted an orphan drug designation to Krystal Biotech’s KB105 for the treatment of patients with transglutaminase 1 (TGM-1) deficient autosomal recessive congenital ichthyosis (ARCI).

Currently, there are no treatments available for the average 20,000 patients affected by this disease worldwide.

"We are pleased to receive [an] orphan drug designation for KB105 to treat ARCI as this is an important step forward in our efforts to bring hope to ARCI patients and their families," said Suma M. Krishnan, founder and chief operating officer of Krystal Biotech, in a recent statement. "We are excited by the results of the pharmacology data in animal models to date for ARCI that we submitted to the Office of Orphan Product Development. We are on track to file an investigational new drug (IND) for KB105 in the fourth quarter of 2018."

A gene therapy, KB105 is a replication-defective, non-integrating viral vector (HSV-1) that has been engineered employing Krystal's STAR-D platform to deliver functional human TGM-1 gene directly to the patients' dividing and non-dividing skin cells, according to Krystal Biotech. HSV-1 is Krystal's replication-deficient, non-integrating viral vector that can penetrate skin cells more efficiently than other viral vectors.

The loss of TGM-1-activity, an essential epidermal enzyme that facilitates the formation of the epidermal barrier, prevents dehydration, and protects the skin from unwanted toxins and surface microorganisms, results in the severe genetic skin disease autosomal recessive congenital ichthyosis (ARCI). Life-long pronounced scaling with increased transepidermal water loss (TEWL) is often exhibited by most patients with a TGM-1-deficiency. The rare disease is associated with increased mortality in the neonatal period and a dramatic impact on quality of life.

While there is preclinical data on KB105 used in animal models, these data have yet to be presented at a conference, a representative from Krystal Biotech told Rare Disease Report^®. Krystal plans to file an investigational new drug (IND) application with the FDA in Q4 2018, which will allow them to bring KB105 into the clinic.