FDA Grants Rare Pediatric Disease Designation for Treatment of Neonatal SP-B Deficiency

The FDA has granted rare pediatric disease designation to AVG-002 (AlveoGene), an inhaled gene therapy, for lethal neonatal surfactant protein B (SP-B) deficiency. SP-B deficiency has an estimated incidence of 1 in 1 million live births, according to a case study published in APJ Reports.^1,2

Pediatric, FDA, Rare Pediatric Disease Designation, SP-B Deficiency | Image Credit: ©jakkapan | stock.adobe.com

The disorder presents as a severe lung disease that requires mechanical ventilation and sometimes cardiopulmonary bypass, with lung transplantation as the only current therapeutic option for long-term survival, according to the authors. SP-B is inherited in SFTPB on chromosome 2, causing partial or complete absence of SP-B. A diagnosis for SP-B can be made via genetic testing in the child as well as both parents. The disorder has a poor prognosis, with children being unlikely to survive beyond the first few months of life, according to the company. Treatment options remain scarce, but gene therapy shows promise as future treatment.^2,3

“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,” David Hipkiss, executive chair of AlveoGene, said in a news release.¹

APV-002 is being developed with the InGenuiTy planform from AlveoGene, which uses a pseudo-typed lentiviral vector to deliver the SP-B gene directly into the neonatal deep lung alveolar region. In preclinical data of murine models, investigators found that a single dose extended survival substantially longer when compared with reported data of other SP-B deficient candidates in development. Investigators also reinforced the findings with restoration of lung histology and function post-treatment in disease-induced lungs.¹

“We similarly expect exciting results with AVG-003, our program in ABCA-3 deficiency, also a life-threatening rare pediatric genetic respiratory disorder, but with 3 to 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,” Hipkiss said in the news release. “In addition, our excellent preclinical progress with AVG-001 for patients with lung disease as a consequence of alpha-1 antitrypsin deficiency, 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.”¹

The company is preparing for clinical development of the drug, with the possibility of filing for marketing authorization by 2028. According to the company, AVG-002 has the potential to be a “first and best-in-class, life-changing product together” than can provide a solution for a disease that currently has none.^1,3

REFERENCES

1. AlveoGene Receives Rare Pediatric Disease Designation (RPDD) from FDA for AVG-002, its Novel, Inhaled Gene Therapy for Lethal Neonatal Surfactant Protein B (SP-B) Deficiency. News release. AlveoGene. November 15, 2024. Accessed November 15, 2024. https://www.globenewswire.com/news-release/2024/11/15/2981801/0/en/AlveoGene-Receives-Rare-Pediatric-Disease-Designation-RPDD-from-FDA-for-AVG-002-its-Novel-Inhaled-Gene-Therapy-for-Lethal-Neonatal-Surfactant-Protein-B-SP-B-Deficiency.html

2. Kurath-Koller S, Resch B, Kraschl R, Windpassinger C, Eber E. Surfactant Protein B Deficiency Caused by Homozygous C248X Mutation-A Case Report and Review of the Literature. AJP Rep. 2015;5(1):e53-e59. doi:10.1055/s-0035-1545668

3. Pipeline. AlveoGene. Accessed November 15, 2024. https://alveogene.com/product-pipeline/