This article explores the significance of this clearance, the potential benefits of KB408, and the path forward for addressing Alpha-1 Antitrypsin Deficiency.
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In a significant development for the treatment of Alpha-1 Antitrypsin Deficiency (AATD), Krystal Biotech, Inc. has received clearance from the U.S. Food and Drug Administration (FDA) for its Investigational New Drug Application (IND) for KB408. This modified, replication-defective, non-integrating HSV-1-derived vector carries two full-length copies of the serpin family A member 1 (SERPINA1) gene, enabling the expression of alpha-1 antitrypsin (AAT). KB408 is formulated for inhaled delivery to the respiratory cells of the lungs via nebulization.
Understanding Alpha-1 Antitrypsin Deficiency
Alpha-1 Antitrypsin Deficiency (AATD) is a rare genetic disease caused by mutations in the SERPINA1 gene. These mutations lead to decreased levels and/or functionality of the AAT protein. In individuals with a PI*ZZ genotype, the most common form of AATD, the body produces misfolded AAT protein that gets trapped inside the liver. This results in low levels of AAT protein in the blood. The deficiency allows inflammation to proceed unchecked and can cause progressive enzymatic destruction of lung tissue, leading to severe respiratory insufficiency and potentially life-threatening pulmonary impairment.
Currently, there is no cure for AATD, and the available treatment options have limitations. Intravenous plasma-derived AAT augmentation therapy, which requires weekly infusions, is one such option. However, its clinical benefits remain to be fully established. The clearance of KB408’s IND by the FDA represents a significant milestone in addressing this serious lung disease with limited treatment options.
KB408, is an inhaled (nebulized) formulation of a novel replication-defective, non-integrating HSV-1-based vector. It is designed to deliver two copies of the SERPINA1 transgene, which encodes for human alpha-1 antitrypsin protein. This innovative gene therapy approach holds promise for the treatment of AATD by increasing levels of functional AAT protein in the lungs.
The inhaled delivery of KB408 via nebulization offers several potential advantages. By directly targeting the respiratory cells of the lungs, KB408 aims to address the root cause of AATD and mitigate the progressive destruction of lung tissue. This targeted approach may also reduce potential off-target effects and enhance the safety and efficacy of the treatment.
Krystal Biotech submitted the IND application for KB408 on August 15th, seeking FDA authorization to initiate a Phase 1 clinical trial. After a 30-day review period, the FDA cleared the IND, allowing the company to proceed with the clinical trial. This clearance is a significant step forward in the development of KB408 as a potential treatment for AATD.
Additionally, on September 5th, the FDA granted orphan drug designation to KB408 for the treatment of AATD. This designation recognizes the need for therapies to address rare diseases and provides incentives to encourage their development.
Phase 1 Clinical Trial and Study Details
The Phase 1 clinical trial of KB408 will be an open-label, single-dose escalation study in adult patients with AATD who have a PI*ZZ genotype. The trial aims to evaluate the safety, tolerability, and efficacy of KB408. Three planned dose levels of KB408 will be evaluated, with three patients in each cohort.
The trial will be conducted in accordance with the clinical trial protocol registered on www.clinicaltrials.gov under the NCT identifier: NCT06049082. The study details, including participant eligibility criteria, treatment procedures, and assessment measures, are available on the clinical trials website.
The FDA’s clearance of Krystal Biotech’s Investigational New Drug Application for KB408 represents a significant step forward in the development of a potential treatment for Alpha-1 Antitrypsin Deficiency. This innovative gene therapy approach, with its targeted inhaled delivery, holds promise for addressing the underlying cause of AATD and improving lung function in affected individuals.
The Phase 1 clinical trial of KB408, set to begin in Q1 2024, will further evaluate the safety, tolerability, and efficacy of this potential treatment. If successful, KB408 could provide a much-needed therapeutic option for individuals with AATD, offering hope for improved quality of life and better disease management.
To learn more about Alpha-1 Antitrypsin Deficiency (AATD) and other gastrointestinal diseases, visit https://checkrare.com/diseases/gastrointestinal-diseases/