EMA Initiates Review of Rocket Pharma's Gene Therapy for Fanconi Anaemia
The European Medicines Agency (EMA) has commenced a review of Rocket Pharmaceuticals' RP-L102, a pioneering gene therapy aimed at treating Fanconi anaemia (FA). This development could herald the first gene therapy option for FA patients in the European Union, offering a new beacon of hope for those affected by this severe genetic disorder.
Understanding Fanconi Anaemia
Fanconi anaemia is an inherited condition that disrupts the body's chromosomal repair mechanisms, leading to bone marrow failure, congenital malformations, and an elevated risk of cancers. Typically diagnosed in children under the age of 12, FA can sometimes remain asymptomatic until adulthood. The disorder is primarily caused by mutations in the FANCA gene, which is crucial for DNA repair, affecting approximately 60% to 70% of FA patients.
RP-L102: A Novel Gene Therapy Approach
RP-L102 utilizes stem cells harvested from the peripheral blood of FA patients, which are then genetically modified using a lentiviral vector to incorporate a functional copy of the FANCA gene. This innovative approach aims to correct the underlying genetic defect responsible for FA, potentially offering a safer alternative to the current standard treatment, allogeneic haematopoietic stem cell transplantation (HSCT). HSCT, while effective, is associated with significant toxicities, especially in the 80% of FA patients lacking an HLA-identical sibling donor.
Clinical Trial Results and Future Prospects
The EMA's review is based on encouraging results from a phase 1/2 trial involving patients with FA-A. The trial demonstrated that a single administration of RP-L102 achieved phenotypic correction in eight out of twelve evaluable patients, with follow-up periods ranging from 12 to 42 months. This correction was evidenced by increased resistance to mitomycin-C (MMC) in bone marrow-derived colony-forming cells, alongside genetic correction and stabilization in blood cell levels. Importantly, the treatment was well-tolerated, with no significant safety signals reported.
Rocket Pharmaceuticals has submitted RP-L102 to the EMA with the aim of preventing bone marrow failure in FA patients, a critical condition that affects 80% of patients within the first decade of life. The company also plans to explore the therapy's efficacy in other forms of FA caused by FANC C and G mutations.
Broader Implications for Rocket Pharmaceuticals
As the FA program nears completion, Rocket Pharmaceuticals is also awaiting a decision from the FDA on Kresladi (marnetegragene autotemcel) for severe leukocyte adhesion deficiency-I (LAD-I), its lead product. The FDA's decision, expected by June 30th, follows a priority review and a request for additional chemistry, manufacturing, and controls (CMC) data, which delayed the application by three months.
Additionally, Rocket is conducting two phase 2 trials of gene therapies for Danon disease and pyruvate kinase deficiency (PKD), further underscoring the company's commitment to advancing gene therapy treatments for rare genetic disorders.
This review of RP-L102 by the EMA represents a significant milestone in the quest for effective treatments for Fanconi anaemia, potentially transforming the therapeutic landscape for patients with this challenging condition.
