Rocket Pharmaceuticals reported positive clinical updates from its phase 2 pivotal trial for Fanconi anemia and phase 1 trials for Danon disease and pyruvate kinase deficiency at the 25th Annual Meeting of the American Society of Gene and Cell Therapy.
Fanconi anemia (FA) is a rare, genetic disorder affecting DNA repair. Approximately two-thirds of FA cases are caused by genetic defects in the FANCA gene, which results in the FA subtype known as FA Complementation Group A (FA-A). FA patients may develop bone marrow failure (very low blood counts), cancers of the blood, or other cancers.
RP-L102 is an experimental gene therapy containing autologous (patient-derived) hematopoietic stem cells (HSCs) that have been genetically modified with a lentiviral vector to contain a functional copy of the FANCA gene. If given early in life, RP-L102 gene therapy has the potential to serve as a preventative measure, correcting bone marrow cells well before bone marrow failure.
In Rocket’s phase 2 pivotal study in Fanconi anemia, five of nine patients sustained increasing bone marrow cell resistance to mitomycin-C (MMC) confirmed over two consecutive timepoints. In these patients, MMC-resistance increased to 51 percent to 94 percent at 18 to 21 months, up from 21 percent to 42 percent at 12 to 18 months. The increase in MMC resistance was accompanied by concomitant genetic markings and hematologic stabilization.
“Addressing the hematologic aspects of Fanconi anemia is essential because this devastating disorder leads to bone marrow failure in the first decade of life,” said Gaurav Shah, CEO of Rocket Pharma. “With these results, we have reached our primary endpoint as defined in the trial protocol and are initiating dialogue with health authorities on next steps forward.”
Danon disease (DD) is a rare genetic disorder that is characterized by severe and primarily hypertrophic cardiomyopathy. Skeletal muscle weakness and mild cognitive impairment are also common. The causative mutation has been identified in the gene encoding for lysosome-associated membrane protein (LAMP2), and in particular the LAMP2B version of the gene which is primarily expressed in heart, skeletal muscle and brain tissue. Affected cells can no longer efficiently digest and recycle protein and other materials, leading to dysfunction in heart, muscle, and brain cells.
RP-A501 is an experimental gene therapy consisting of a recombinant adeno-associated serotype 9 (AAV9) capsid containing a functional version of the human LAMP2B transgene (AAV9.LAMP2B) which is administered as a single intravenous infusion. RP-A501 has the potential to restore normal cardiac function in patients with Danon disease.
“We are highly encouraged by the initial safety data from the two pediatric patients in the phase 1 Danon Disease trial that suggest RP-A501 was well-tolerated,” said Shah. “These two patients had markedly reduced complement activation and no complement-related adverse events. They received preventative therapy with a modified immunosuppressive regimen. We believe today’s results represent an important step forward in optimizing the safety of AAV9-based gene therapy for Danon Disease and the Danon patient community.”
Updated data are anticipated in the third quarter.
Finally, Rocket provided interim results from an ongoing global phase 1 study of its experimental gene therapy for pyruvate kinase deficiency (PKD) in a poster presentation.
PKD is a rare, genetic blood disorder. PKD is caused by a defect in the PKLR gene which is responsible for energy production in red blood cells (RBCs). RBCs carry oxygen to the rest of the body. When the PKLR gene has a defect, RBCs are limited in their ability to produce energy and remain intact. As a result, patients with PKD frequently have anemia, chronic fatigue, yellowing of the skin and eyes (jaundice) and enlarged spleens.
RP-L301 is a gene therapy product containing autologous (patient-derived) hematopoietic stem cells (HSCs) that have been genetically modified with a lentiviral vector to contain a functional copy of the PKLR gene. RP-L301 has the potential to correct multiple disease elements associated with PKD.
The poster presentation includes data (cut-off April 13, 2022) from two adult patients with significant anemia who were treated with RP-L301, Rocket’s ex vivo lentiviral gene therapy candidate for PKD. At 18 months post-infusion, both patients have sustained transgene expression, normalized hemoglobin, improved hemolysis, no red blood cell transfusion requirements post-engraftment, and improved quality of life both reported anecdotally and as documented via formal quality of life assessments.
The safety profile of RP-L301 appears favorable, with no serious adverse events 18 months post-infusion. Transient transaminase elevation was seen in both patients post-therapy/conditioning, with no clinical stigmata of liver injury and subsequent resolution without clinical sequelae.
The pediatric cohort is currently enrolling.
Author: Rare Daily Staff
Stay Connected
Sign up for updates straight to your inbox.