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FDA Accepts IND Application for Cystic Fibrosis Gene Therapy KB407

The phase 1 clinical trial from Krystal Biotech is expected to begin this year.

The FDA has accepted the investigational new drug (IND) application for Krystal Biotech’s KB407, a gene therapy candidate being evaluated for the treatment of cystic fibrosis (CF).1 A phase 1 clinical trial for KB407 (NCT05095246) is expected to begin in the second half of 2022.

KB407 is redosable and functions via a modified replication-incompetent HSV-1 vector which delivers 2 full-length functional copies of the cystic fibrosis transmembrane conductance regulator gene (CFTR) to respiratory cells in the lungs, allowing for restoration of ion and water flow into and out of lung cells, regardless of a patient's specific disease-causing mutation.

“We are excited to advance KB407, our investigational gene therapy for patients with CF, into the clinic. It is designed to treat the root cause of the disease regardless of an individual patient’s mutation by giving the body instructions to produce its own functional protein,” Hubert Chen, MD, senior vice president of clinical development at Krystal Biotech said in a statement.1 “In addition, this IND acceptance represents an important milestone for us as it allows us to demonstrate the power of our platform to deliver genes, beyond skin cells, to respiratory cells.”

The open label clinical trial is expected to enroll up to 20 male and female participants aged 18 years and older who have a confirmed diagnosis of CF that is deemed clinically stable. Patients who have initiated or changed a chronic therapy within 28 days of Day 0, patients with a history of lung transplantation, and those with an active oral herpes infection within 30 days of Day 0 or an HSV-1 wild type seropositive screening will be excluded from the study.

The trial will consist of 3 experimental cohorts. Four patients in cohort 1 will receive a single dose of KB407 via nebulized solution or intradermal injection at Day 0; 4 patients in cohort 2 will receive 2 doses of KB407 administered at Day 0 and Day 14 via nebulized solution; and 5 patients in cohort 3 will receive 4 doses of KB407 administered at Day 0, Day 7, Day 14, and Day 21 via nebulized solution. Patients in the first cohort may roll over into cohort 2 at their 28-day visit, and all patients will be followed for 1 year after their last dose. The primary end point is safety and tolerability measured by the number of participants who experience treatment-related adverse events. The secondary end point will evaluate changes in lung function from baseline via assessment of forced expiratory volume in 1 second.

Krystal Biotech previously received approval for a phase 1 clinical trial from the Bellberry Human Research Ethics Committee in Australia in September of last year.2 

“There remains need for a genetically corrective CF therapy that can help lung cells make full-length, normal CFTR protein in any CF patient - KB407 was designed to do just that,” Suma Krishnan, chief operating officer of Krystal Biotech, said in a statement at that time.2 “While COVID related delays have presented a challenge, we look forward to initiating this proof-of-concept trial in Australia in the coming weeks and initiating a clinical trial in the US in 2022.”

The US study is now estimated to be completed by October 30, 2024.

1. Krystal Biotech announces FDA acceptance of KB407 IND application for cystic fibrosis clinical trial. News release. Krystal Biotech, Inc. August 1, 2022. https://ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-announces-fda-acceptance-kb407-ind-application
2. Krystal Biotech receives approval from the Human Research Ethics Committee in Australia for phase 1 trial of KB407 for cystic fibrosis. News release. Krystal Biotech, Inc. September 29, 2021.https://ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-receives-approval-human-research-ethics