Rocket Pharmaceuticals To Publish Manuscript Evaluating Mosaicism In Fanconi Anemia

Rocket Pharmaceuticals Inc. a clinical-stage company that is advancing an integrated as well as sustainable pipeline of genetic therapies for rare childhood disorders, has announced that it will publish a peer-reviewed manuscript.

In the journal Annals of Hematology, this manuscript is the first comprehensive review of somatic mosaicism in Fanconi Anemia (FA). The review has been titled as “Mosaicism in Fanconi Anemia: Concise review and evaluation of published cases with focus on clinical course of blood count normalization.”

This review summarizes the existing literature regarding mosaicism in FA. Earlier the term used to describe mosaicism was “natural gene therapy.” Mosaicism occurs when a spontaneous second mutation occurs in an (already-mutated) FA gene. This mutation results in a functional FA protein and restored cellular DNA-repair capacity. When this type of reversion or compensatory mutation happens in hematopoietic stem cells (HSCs), then sometimes, these cells can be capable of restoring a more normalized blood and bone marrow environment.

In some cases, restoration takes multiple decades. The review provides the FA community with an additional resource, ensuring a better understanding of the phenomenon. It also supports Rocket’s approach of treating patients with RP-L102, the Company’s gene therapy candidate for FA. This approach does not have any pre-treatment conditioning regimen.

Jonathan Schwartz, M.D., Chief Medical Officer and Senior Vice President of Rocket says:

“Although mosaicism in FA has been discussed within the physician and research community for more than two decades, uncertainty about the clinical significance of reversion mutations has remained. Importantly, findings from this review support the selective growth advantage for gene corrected stem cells over diseased stem cells which potentially obviates the need for conditioning in FA gene therapy. In addition to allowing us to better understand how RP-L102 may best help patients, we hope that bringing these data together into a cohesive review can better help the entire FA community as we work together to optimize treatment options.”

This upcoming publication covers not only a literature-based assessment of FA mosaicism, but also it also identifies a cohort of cases that most likely emanated from reversion in long-term repopulating HSC populations.

Additionally, the manuscript does detail the diagnostic methods, along with the outcomes of published cases of mosaicism. Based on evaluation, the cases have been selected on the basis of FA mosaic patients being followed long-term in a clinical setting. These findings shed light on what happens after treatment with Rocket’s gene therapy candidate, RP-L102. Here, additional detail on the mechanism and chronology by which gene corrected cells can repopulate patients’ blood as well as bone marrow, have been listed. RP-L102 is currently being investigated in a global Phase 2 registration-enabling study.