Inherited SP-B deficiency is a genetic disorder affecting approximately 1 in 1 million newborns in the US and Europe. It results from mutations in the SP-B gene, which is essential for lung function and survival.
Current 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only provide temporary relief, and once genetic diagnosis of SP-B deficiency is confirmed, treatment is usually withdrawn and patients die.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. This leaves few if any viable options for long-term survival.
Professor Deborah Gill says: 'It must be devastating to be told that your newborn baby has a fatal disease for which there is no treatment. Surfactant protein B (SPB) deficiency is a rare disease where a baby is born with severe breathing difficulties. The babies cannot keep their lungs inflated and need mechanical ventilation to help keep them alive. Currently, there is no cure or treatment for this disease, but we think gene therapy could help. We aim to deliver a functional copy of the gene responsible for SPB deficiency deep into the babies' lungs to help them make normal lung surfactant so they can breathe independently.'
AlveoGene, co-founded in 2023 by Professor Deborah Gill and Professor Steve Hyde, is developing a gene therapy known as AVG-002 using its InGenuiTy® platform. This uses a unique 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.
We have strong evidence that a single dose of our gene therapy could offer a treatment for SPB-deficiency and this has been acknowledged by the Food & Drug Administration in awarding us this Rare Pediatric Disease Designation. The development and testing of new gene therapies takes a long time currently, but this is one way we hope to speed up the process. - Professor Deborah Gill
AlveoGene has now been awarded a Rare Pediatric Disease Designation (RPDD) by the US Food & Drug Administration (FDA) for AVG-002. This means that it will receive a rare paediatric disease Priority Review Voucher (PRV) when the designated drug is approved for the associated indication in the paediatric population.
The voucher will reduce the product's review time and accelerate 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.
Preclinical data in SP-B gene knock-out mouse 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. This offers 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. AlveoGene is therefore 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.
AlveoGene was founded in 2023 by Oxford Science Enterprises, Harrington Discovery Institute and Old College Capital in partnership with six leading scientists from the world-renowned UK Respiratory Gene Therapy Consortium (GTC). It is the first company being advanced under the Oxford-Harrington Rare Disease Centre's Therapeutics Accelerator.