Phase 1 Trial for CF Gene Therapy KB407 to Open in US

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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CF gene therapy | Cystic Fibrosis News Today | US trial of KB407 gene therapy | illustration noting a clinical trial

A Phase 1 clinical trial of an experimental inhalation gene therapy for cystic fibrosis (CF) — KB407 by Krystal Biotech — was given clearance to start by the U.S. Food and Drug Administration (FDA).

Expected to begin this year, the study aims to enroll 20 adults with CF who will be assigned to one of three sequential groups and treated with ascending doses of KB407, administered via a nebulizer. The potential therapy is designed to treat all patients, regardless of underlying CFTR gene mutation.

“We are excited to advance KB407, our investigational gene therapy for patients with CF, into the clinic,” Hubert Chen, MD, senior vice president of clinical development at Krystal, said in a press release.

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The trial’s main goal is to evaluate the safety and tolerability of KB407. Therapy effect on lung function, a secondary goal, will be assessed by measuring forced expiratory volume in one second (FEV1), a test of how much air someone can forcibly exhale in a second.

Phase 1 trial of CF gene therapy underway in Australia

Krystal was given the go-ahead last year for a separate Phase 1 trial (NCT05095246) testing KB407 in up to 13 adults with stable CF at a single site in Australia.

Like the upcoming U.S. trial, this study primarily aims to explore the experimental therapy’s safety profile, with lung function measures as a secondary outcome. Recruitment is currently ongoing at Hunter Medical Research Institute in Newcastle, New South Wales, and this trial is due to conclude in October 2024.

More than 2,000 mutations in the CFTR gene are known to cause CF. KB407 aims to deliver two healthy copies of this gene to cells in the lungs, and it has been specifically designed to allow for repeat and adjusted dosing, according to Krystal.

“[KB407] 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,” Chen said.

The therapy delivers its genetic cargo using a vector that was created by modifying herpes simplex virus 1 (HSV-1), commonly known as causing oral herpes. Preclinical research in animal models suggested that KB407 is safe and can deliver the CFTR gene to lung cells as intended.