AlveoGene (or ‘the Company’, www.alveogene.com), a company focused on transforming rare respiratory disease outcomes using inhaled gene therapy, announces that it has been granted a Rare Pediatric Disease Designation (RPDD) by the US Food & Drug Administration (FDA) for AVG-002, its novel inhaled gene therapy for lethal neonatal Surfactant Protein B (SP-B) deficiency.

Inherited SP-B deficiency is an ultra-rare monogenic cause of fatal respiratory distress syndrome in newborn infants with very limited treatment options. This genetic disorder, affecting approximately 1 in 1 million newborns in the US and Europe, results from mutations in the SP-B gene, which is essential for lung function and survival. Current treatments are mainly supportive, including mechanical ventilation and surfactant replacement, however these interventions only provide temporary relief and once genetic diagnosis of SP-B deficiency is confirmed, treatment is usually withdrawn and patients die. The only definitive treatment, lung transplantation, is often not accessible owing to the scarcity of donor organs for newborns and the risks involved, leaving few if any viable options for long-term survival.

AVG-002 is being developed by AlveoGene using its InGenuiTy® platform, which employs a unique pseudotyped lentiviral vector to deliver a functional SP-B gene directly to the neonatal deep lung alveolar region with high efficiency and efficacy via respiratory instillation.

Preclinical data in SP-B gene knock-out murine models demonstrate that a single dose of AVG-002 extends survival substantially longer when compared with reported data of other SP-B deficiency candidates in development, offering the possibility of a lifelong treatment from a single administration. These data are further reinforced by findings that confirm the restoration of normal lung histology and function following AVG-002 treatment in disease-induced lung tissues. Based on these highly encouraging findings, AlveoGene is advancing its preparations for the clinical development of AVG-002 in lethal neonatal SP-B deficiency with the possibility of filing for marketing authorisation by 2028.

David Hipkiss, Executive Chair of AlveoGene, said: “This Rare Pediatric Disease Designation (RPDD) for AVG-002 marks a significant step forward in our mission to develop transformative treatments for children with fatal genetic lung diseases. Receiving this RPDD not only underscores the urgent need for innovative therapies in this area but also highlights the potential of our approach in SP-B deficiency in newborn infants, which is designed to target the affected lung tissues directly, restore vital function and provide a viable therapeutic solution where presently there is none.

“We similarly expect exciting results with AVG-003, our programme in ABCA-3 deficiency, also a life-threatening rare pediatric genetic respiratory disorder, but with 3-5 times greater incidence than SP-B deficiency. AVG-003 leverages the same novel InGenuiTy® platform technology as AVG-002, and we are optimistic that it might also meet the criteria for an RPDD as we advance its development.

“In addition, our excellent preclinical progress with AVG-001 for patients with lung disease as a consequence of Alpha-1 Antitrypsin Deficiency (AATD), continues to give us confidence that it could become a best-in-class treatment that targets the lung directly where its impact on morbidity and mortality is highest and patient numbers are the greatest.”

Rare pediatric diseases are defined by the FDA as serious or life-threatening conditions primarily affecting children under 18, with fewer than 200,000 cases in the US. Companies awarded an RPDD receive a rare pediatric disease Priority Review Voucher (PRV) from the FDA when the designated drug is approved for the associated indication in the pediatric population. The voucher allows the recipient company to obtain FDA priority review of either a New Drug Application (NDA) or Biologics License Application (BLA) for a different product and/or indication, reducing the review time and accelerating any granted approval and subsequent market entry by at least four months. The PRV may be used by the original recipient, or it can be sold to another company for the purchaser’s use, with PRVs recently achieving sales prices of $100-$150 million.

Executive Chair, David Hipkiss, will present an overview of AlveoGene and its innovative technology and pipeline  at the Inv€$tival Showcase on Monday 19 November at 15.00 hrs GMT at the Tobacco Dock in London, UK.