News Release Details
Rocket Pharmaceuticals Presents Positive Data from LV Hematology and AAV Cardiovascular Gene Therapy Programs at the 26th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT)
May 19, 2023
Robust and sustained efficacy in both adult PKD patients up to 30 months post-RP-L301; first pediatric patient results suggest efficacy similar to adult cohort with initial greater than five-point increase in hemoglobin
Sustained genetic correction observed in eight of 12 evaluable Fanconi Anemia patients, and phenotypic correction and concomitant hematologic stabilization observed in seven of 12 patients 12-42 months after RP-L102 in Phase 2 pivotal trial
100% overall survival at 12 months post-RP-L201 and favorable safety profile for all LAD-I patients with 12-24 months of follow-up
Robust preclinical proof of concept studies showed RP-A601 for PKP2-ACM decreased arrhythmias and increased survival
“I am pleased that we continue to deliver outstanding clinical results that highlight the momentum across both our LV hematology and AAV cardiovascular platforms,” said
Global Phase 1 Study Results of Lentiviral Mediated Gene Therapy for Severe Pyruvate Kinase Deficiency (PKD)
The oral presentation includes positive updated data (cut-off
- Robust and sustained efficacy in both adult patients up to 30 months post-infusion demonstrated by normalized hemoglobin (from baseline levels in the 7.0-7.5 g/dL range), improved hemolysis parameters, and red blood cell transfusion independence.
- Both adult patients reported improved quality of life with documented improvements via formal quality of life assessments.
- The safety profile appears highly favorable, with no RP-L301-related serious adverse events in either of the adult patients. Previously reported transient transaminase elevation seen in both adult subjects post conditioning and infusion with no clinical stigmata of liver injury have fully resolved.
- Insertion site analyses in peripheral blood and bone marrow in both adult patients through 24 months post-RP-L301 demonstrated highly polyclonal patterns and there has been no evidence of insertional mutagenesis.
- First pediatric results suggest similar efficacy as observed in long-term efficacy data in the adult cohort.
- The first pediatric patient infusion of RP-L301 was well tolerated, with engraftment achieved at day +15, hospital discharge less than one month following infusion, and no RP-L301-related serious adverse events.
- Hemoglobin normalized six weeks post-infusion and measured 13.4 g/dL at eight weeks (from median baseline of 7.9 g/dL). There were no red blood cell transfusion requirements following engraftment.
- Adult and pediatric enrollment is completed in the Phase 1 study. Phase 2 pivotal trial initiation is anticipated in the fourth quarter of 2023.
Lentiviral-Mediated Gene Therapy for Fanconi Anemia [Group A]: Results from Global RP-L102 Clinical Trials
The oral presentation includes positive, updated data (cut-off
- RP-L102 conferred sustained genetic correction in eight of 12 evaluable patients and comprehensive phenotypic correction in seven of 12 evaluable patients with ≥12 months of follow up as demonstrated by increased resistance to mitomycin-C (MMC) in bone marrow (BM)-derived colony forming cells and hematologic stabilization.
The safety profile of RP-L102 remains highly favorable with no significant safety signals, and the treatment, administered without any cytotoxic conditioning, continues to be well tolerated. No signs of bone marrow dysplasia, clonal dominance or insertional mutagenesis related to RP-L102 have been observed.
- Polyclonal integration patterns have been observed in each of the seven patients with phenotypic, genetic, and hematologic evidence of engraftment.
- Pivotal trial enrollment and treatment have been completed, and the final two patients have been treated with commercial drug product in preparation for launch.
- Based on the positive efficacy and safety data from the Phase 2 pivotal FA trial, Rocket anticipates filing the Biologics License Application (BLA) with the FDA in the fourth quarter of 2023.
Autologous Ex Vivo Lentiviral Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I): Interim Results from an Ongoing Phase 1/2 Study
The poster presentation includes positive, updated top-line data (cut-off
Observed 100% overall survival at 12 months post-infusion via
Kaplan Meierestimate for all nine LAD-I patients with 12 to 24 months of available follow-up. Data also showed evidence of resolution of LAD-I-related skin rash and restoration of wound repair capabilities.
- The safety profile of RP-L201 was highly favorable in all patients with no RP-L201-related serious adverse events to date. Adverse events related to other study procedures, including busulfan conditioning, have been previously disclosed and are consistent with the safety profiles of those agents and procedures.
- Based on the positive efficacy and safety data from the Phase 2 pivotal LAD-I trial, Rocket anticipates filing the Biologics License Application (BLA) with the FDA during this second quarter of 2023.
Danon Disease Phase
The spotlight oral presentation includes positive, previously disclosed data (cut-off
- As previously disclosed, RP-A501 was associated with favorable safety at the low dose with an appropriate immunomodulatory regimen. There have been no RP-A501-related or steroid-related serious adverse events reported to date in the pediatric cohort.
- Efficacy results continue to demonstrate sustained improvement or stabilization in all patients with preserved left ventricular systolic function at time of treatment (n=6, across all cohorts) across key clinical, biomarker, echocardiographic, and quality of life parameters.
- Improvement or stabilization of disease progression in these patients treated with RP-A501, as measured by natriuretic peptides, is in direct contrast to progressive worsening observed over three to 30 months in patients in the prospective natural history study.
- As of the presentation, all six patients that remain in follow-up continue to show signs of improvement or stabilization; additional follow-up data to be provided at a future date.
- The Phase 2 pivotal trial of RP-A501 for Danon Disease remains on track for initiation during this second quarter of 2023.
Preclinical Efficacy of AAVrh.74-PKP2a (RP-A601): Gene Therapy for PKP2-associated Arrhythmogenic Cardiomyopathy
The late-breaking abstract presentation includes robust preclinical proof of concept for RP-A601, Rocket’s investigational AAV gene therapy for the treatment of arrhythmogenic cardiomyopathy due to plakophilin 2 pathogenic variants (PKP2-ACM), a devastating inherited heart disease that can lead to life-threatening arrhythmias, cardiac structural abnormalities, and sudden cardiac death. PKP2-ACM affects approximately 50,000 people in the
- The current standard of care for patients with PKP2-ACM consists of medical therapy, implantable cardioverter defibrillators (ICDs), and ablations, which are not curative. Even with treatment, life-threatening arrhythmias and progression of disease still occur.
- Preclinical proof of concept from a translationally relevant animal model has been demonstrated following Rocket-sponsored studies with academic partners. The preclinical studies with a cardiomyocyte-specific PKP2 knockout mouse model of ACM evaluated initial proof of concept and dose-related effects of AAV vectors (RP-A601), including survival, functional and anatomic benefits. Notably, the studies evaluated the delivery of RP-A601 at seven- and 14-days following induction of PKP2 knockout and subsequent disease onset.
Results demonstrated increased survival and preserved cardiac function in the PKP2 knockout mouse model following administration of RP-A601.
- 100% of adult PKP2 knockout mice receiving RP-A601 seven days after knockout induction demonstrated survival to the five-month duration of evaluation, compared to 100% mortality by approximately day 50 in PKP2 knockout mice receiving formulation control. PKP2 knockout mice receiving RP-A601 displayed preserved ejection fraction and right ventricular area at 28 days, sustained to five months.
- Fourteen days following RP-A601 administration, PKP2 knockout mice demonstrated robust survival with a similar degree of cardiac benefit through five months. RP-A601 was also associated with mitigation of isoproterenol-induced premature ventricular contractions (PVCs) and arrhythmias, which are major morbidity components of ACM.
- Based on robust preclinical proof of concept that has demonstrated decreased arrhythmias and increased survival and the completion of extensive IND-enabling toxicology studies, Rocket has received IND clearance from the FDA for a Phase 1 study of RP-A601 that will assess the impact of RP-A601 on PKP2 myocardial protein expression, cardiac biomarkers, and clinical predictors of life-threatening ventricular arrhythmias and sudden cardiac death.
- Rocket is initiating Phase 1 study start-up activities and rapidly advancing the first investigational gene therapy for PKP2-ACM into the clinic.
About Pyruvate Kinase Deficiency
Pyruvate Kinase Deficiency (PKD) is a rare, monogenic red blood cell disorder resulting from a mutation in the PKLR gene encoding for the pyruvate kinase enzyme, a key component of the red blood cell glycolytic pathway. Mutations in the PKLR gene result in increased red blood cell destruction and the disorder ranges from mild to life-threatening anemia. PKD has an estimated prevalence of 4,000 to 8,000 patients in the
RP-L301 was in-licensed from the Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) and Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz (IIS-FJD).
About Fanconi Anemia
Fanconi Anemia (FA) is a rare pediatric disease characterized by bone marrow failure, malformations, and cancer predisposition. The primary cause of death among patients with FA is bone marrow failure, which typically occurs during the first decade of life. Allogeneic hematopoietic stem cell transplantation (HSCT), when available, corrects the hematologic component of FA, but requires myeloablative conditioning. Graft-versus-host disease, a known complication of allogeneic HSCT, is associated with an increased risk of solid tumors, mainly squamous cell carcinomas of the head and neck region. Approximately 60-70% of patients with FA have a Fanconi Anemia complementation group A (FANCA) gene mutation, which encodes for a protein essential for DNA repair. Mutations in the FANCA gene leads to chromosomal breakage and increased sensitivity to oxidative and environmental stress. Increased sensitivity to DNA-alkylating agents such as mitomycin-C (MMC) or diepoxybutane (DEB) is a ‘gold standard’ test for FA diagnosis. Somatic mosaicism occurs when there is a spontaneous correction of the mutated gene that can lead to stabilization or correction of a FA patient’s blood counts in the absence of any administered therapy. Somatic mosaicism, often referred to as ‘natural gene therapy’ provides a strong rationale for the development of FA gene therapy because of the selective growth advantage of gene-corrected hematopoietic stem cells over FA cells. There is a high unmet medical need for patients with FA.
About Leukocyte Adhesion Deficiency-I
Severe Leukocyte Adhesion Deficiency-I (LAD-I) is a rare, autosomal recessive pediatric disease caused by mutations in the ITGB2 gene encoding for the beta-2 integrin component CD18. CD18 is a key protein that facilitates leukocyte adhesion and extravasation from blood vessels to combat infections. As a result, children with severe LAD-I are often affected immediately after birth. During infancy, they suffer from recurrent life-threatening bacterial and fungal infections that respond poorly to antibiotics and require frequent hospitalizations. Children who survive infancy experience recurrent severe infections including pneumonia, gingival ulcers, necrotic skin ulcers, and septicemia. Without a successful bone marrow transplant, mortality in patients with severe LAD-I is 60-75% prior to the age of 2 and survival beyond the age of 5 is uncommon. There is a high unmet medical need for patients with severe LAD-I.
Rocket’s LAD-I research is made possible by a grant from the
About Danon Disease
Danon Disease is a rare X-linked inherited disorder caused by mutations in the gene encoding lysosome-associated membrane protein 2 (LAMP-2), an important mediator of autophagy. This results in accumulation of autophagosomes and glycogen, particularly in cardiac muscle and other tissues, which ultimately leads to heart failure, and for male patients, frequent death during adolescence or early adulthood. It is estimated to have a prevalence of 15,000 to 30,000 patients in the
About PKP2-Arrhythmogenic Cardiomyopathy (PKP2-ACM)
PKP2-ACM is an inherited heart disease caused by mutations in the PKP2 gene and characterized by life-threatening ventricular arrhythmias, cardiac structural abnormalities, and sudden cardiac death. PKP2-ACM affects approximately 50,000 adults and children in the
Rocket Cautionary Statement Regarding Forward-Looking Statements
Various statements in this release concerning Rocket’s future expectations, plans and prospects, including without limitation, Rocket’s expectations regarding the safety and effectiveness of product candidates that Rocket is developing to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), Danon Disease (DD) and other diseases, the expected timing and data readouts of Rocket’s ongoing and planned clinical trials, the expected timing and outcome of Rocket’s regulatory interactions and planned submissions, Rocket’s plans for the advancement of its Danon Disease program, including its planned pivotal trial, and the safety, effectiveness and timing of related pre-clinical studies and clinical trials, may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. You should not place reliance on these forward-looking statements, which often include words such as “aim,” “anticipate,” "believe," “can,” “continue,” “design,” “estimate,” "expect," "intend," “may,” "plan," “potential,” "will give," "seek," "will," "may," "suggest" or similar terms, variations of such terms or the negative of those terms. Although Rocket believes that the expectations reflected in the forward-looking statements are reasonable, Rocket cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Rocket’s ability to monitor the impact of COVID-19 on its business operations and take steps to ensure the safety of patients, families and employees, the interest from patients and families for participation in each of Rocket’s ongoing trials, patient enrollment, trial timelines and data readouts, our expectations regarding our drug supply for our ongoing and anticipated trials, actions of regulatory agencies, which may affect the initiation, timing and progress of pre-clinical studies and clinical trials of its product candidates, our ability to submit regulatory filings with the