FDA Grants RPDD to AlveoGene's Inhaled Gene Therapy AVG-002 for Lethal Neonatal SP-B Deficiency

AlveoGene, a company dedicated to transforming outcomes for rare respiratory diseases through inhaled gene therapy, recently secured a Rare Pediatric Disease Designation (RPDD) from the US Food & Drug Administration (FDA) for its innovative treatment, AVG-002. This treatment targets lethal neonatal Surfactant Protein B (SP-B) deficiency, a genetic disorder causing fatal respiratory distress syndrome in newborns.

Inherited SP-B deficiency is an extremely rare genetic condition, affecting about 1 in every million live births in the US and Europe. This disorder is caused by mutations in the SP-B gene, which is crucial for lung function and survival. Current treatment options are limited mostly to supportive measures, such as mechanical ventilation and surfactant replacement, which only offer temporary relief. In many cases, once a genetic diagnosis of SP-B deficiency is confirmed, treatment is usually withdrawn, resulting in the infant's death. Lung transplantation is the only definitive treatment, but it is often not feasible due to the scarcity of donor lungs suitable for newborns and the associated risks.

AlveoGene’s AVG-002 is being developed using the company's proprietary InGenuiTy® platform, which utilizes a unique pseudotyped lentiviral vector to efficiently deliver a functional SP-B gene directly to the deep lung alveolar regions of newborns through respiratory instillation. Preclinical studies using SP-B gene knock-out murine models have shown that a single dose of AVG-002 significantly extends survival compared to other SP-B deficiency treatments currently in development. These studies also indicate the potential for lifelong treatment from just one administration, with data showing restored normal lung histology and function in treated lung tissues.

Encouraged by these promising preclinical results, AlveoGene is preparing for the clinical development of AVG-002, aiming to file for marketing authorisation by 2028. David Hipkiss, Executive Chair of AlveoGene, highlighted the importance of the RPDD for AVG-002, emphasizing the urgent need for innovative therapies for fatal genetic lung diseases in children. This designation not only underscores the significance of their approach but also paves the way for potentially life-saving treatments targeting the affected lung tissues directly.

In addition to AVG-002, AlveoGene is also developing AVG-003 for ABCA-3 deficiency, another severe rare pediatric genetic respiratory disorder with a higher incidence than SP-B deficiency. AVG-003 leverages the same InGenuiTy® platform technology, and AlveoGene is hopeful it will also qualify for an RPDD as development progresses.

Moreover, AlveoGene continues to achieve excellent preclinical progress with AVG-001, aimed at treating patients with lung disease resulting from Alpha-1 Antitrypsin Deficiency (AATD). AVG-001 is designed to promote localized production of alpha-1 antitrypsin in the lungs, offering a potential alternative to the current standard-of-care therapy, which involves weekly intravenous protein replacement.

AlveoGene, founded in 2023 by Oxford Science Enterprises, Harrington Discovery Institute, and Old College Capital in collaboration with six leading scientists from the UK Respiratory Gene Therapy Consortium (GTC), is the first company to advance under the Oxford-Harrington Rare Disease Centre’s Therapeutics Accelerator. The GTC, comprising researchers from Imperial College London, and the Universities of Oxford and Edinburgh, has developed the pseudotyped lentiviral vector technology that underpins AlveoGene’s InGenuiTy® platform.

Executive Chair David Hipkiss will present an overview of AlveoGene and its innovative pipeline at the Inv€$tival Showcase on 19 November in London, UK.