Krystal Biotech Provides Update on the Clinical Trial Evaluating Topical KB105 for the Treatment of TGM-1 Associated Ichthyosis
July 01, 2021 at 04:15 pm EDT
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Krystal Biotech Inc. announced updated results from the Phase 1/2 clinical trial evaluating topical administration of KB105 in patients with autosomal recessive congenital ichthyosis (ARCI) associated with mutations in the TGM1 gene. These data show that repeat doses of KB105 continue to be well tolerated with no adverse events and with no evidence of immune response, systemically or at the sites of application. Phenotypic improvement, based on the IGA scale, was observed at each KB105 dosing site at varying time points throughout the 30-day dosing period, with the maximum effect observed in the treatment areas that received the highest KB105 dose. These results build on previous data showing a dramatic increase in KB105-mediated TGM-1 expression and activity in 3 patients, which correlated with an improvement on the IGA scale after KB105 topical treatment, with or without pretreatment of the area through micro-needling. No drug-related adverse effects were reported. Initial Phase 2 Data: An adult subject, aged 63, was enrolled and four 100cm2 treatment areas were identified. Each treatment area was assigned to receive repeat doses of 4.0x109 PFU (n=2 treatment areas) or 1.0x1010 PFU (n=2 treatment areas). Each area was dosed on Day 1 and 3, after which dosing continued either every 3 days (n=2 treatment areas) or every 6 days (n=2 treatment areas) up to day 30. Treatment areas were clinically evaluated at pre- and post-KB105 application timepoints, using a 5-point IGA scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = very severe). Repeated topical doses of KB105 were well tolerated, and no drug-related adverse effects were reported. No vector shedding or systemic viral exposure was detected at any time point. Improvement on the IGA scale was observed in each treatment area, with the maximum effect observed in TA3 and TA4 that received the highest dose; at day 27, the investigator assigned an IGA score of 2, which was improved as compared to baseline score of 4 in each area. Variable 1-point improvements were observed at other time points and in the treatment areas that received the lowest dose. As in the Phase 1 portion of the trial, TGM1 turnover was observed to be variable but relatively rapid, and the observed IGA improvements were not sustained through day 60.
Krystal Biotech, Inc. is an integrated, commercial-stage biotechnology company. It is focused on the discovery, development, and commercialization of genetic medicines to treat diseases with high unmet medical needs. Its product candidates in various stages of clinical and preclinical development include VYJUVEK, KB407, KB408, KB707, KB105, KB104, KB104, and KB301. Its commercial product VYJUVEK is a non-invasive, topical, redo sable gene therapy designed to deliver two copies of theCOL7A1 gene when applied directly to DEB wounds. VYJUVEK is designed to treat DEB at the molecular level by providing the patientâs skin cells the template to make normal COL7 protein, thereby addressing the fundamental disease-causing mechanism. KB407 is developed for the treatment of Cystic Fibrosis. KB408 is developed for the treatment of Alpha-1 Antitrypsin Deficiency. KB707 is developed for the treatment of solid tumors. KB105 is developed for TGM1-Deficient Autosomal Recessive Congenital Ichthyosis.