FDA Grants Krystal Biotechs Rare Pediatric Disease Designation for Gene Therapy for Congenital Ichthyosis

Rare Daily Staff

The U. S. Food and Drug Administration granted Krystal Biotech a Rare Pediatric Disease designation for its experimental gene therapy KB105 for the treatment of patients with TGM-1-deficient autosomal recessive congenital ichthyosis (ARCI), a rare, life-threatening disease.

Transglutaminase 1 (TGM-1) is an essential epidermal enzyme that facilitates the formation of the epidermal barrier, which prevents dehydration, and protects the skin from unwanted toxins and surface microorganisms. The loss of TGM-1-activity results in ARCI. Most patients with a TGM-1-deficiency exhibit life-long pronounced scaling with increased transepidermal water loss. The scales are plate-like, often of a dark color, and cover the whole body surface area. TGM-1-deficient ARCI is associated with increased mortality in the neonatal period and has a dramatic impact on quality of life. No efficient treatment is available; current therapy only relieves some symptoms.

KB105 is Krystal’s second product candidate, currently in preclinical development, and seeks to use gene therapy to treat patients with TGM-1 deficient ARCI. KB105 is a replication-defective, non-integrating viral vector 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. HSV-1 is Krystal’s replication-deficient, non-integrating viral vector that can penetrate skin cells more efficiently than other viral vectors. Its high payload capacity allows it to accommodate large or multiple genes and its low immunogenicity makes it a suitable choice for direct and repeat delivery to the skin.

The FDA grants Rare Pediatric Disease designation for serious or life-threatening diseases with manifestations in individuals aged from birth to 18 years, including access to the FDA’s expedited review and approval process. The designation makes the KB105 program eligible for a Rare Pediatric Disease Priority Review Voucher upon approval of KB105 by the FDA.

The vouchers can be used to reduce the time of an FDA new drug approval review to six months from ten months. The vouchers are potentially lucrative because they are transferable. Most recently, Ultragenyx and Kyowa Hakko Kirin sold their Priority Review Voucher for $80.6 million.

“We are motivated by compassion and urgency for the patients, families and caregivers affected by ARCI and other serious, life-threatening conditions with high unmet needs,” said Suma Krishnan, founder and chief operating officer of Krystal Biotech. “This designation, combined with our receipt of the FDA’s Orphan Drug designation for KB105 earlier this month, will help support our efforts to speed up the drug development efforts in this indication and, when successful, enable this new therapeutic candidate to be made available to patients as soon as possible.”

August 23, 2018
Photo: Suma Krishnan, founder and chief operating officer of Krystal Biotech