Rocket Pharmaceuticals (RCKT) Reports Preliminary Data from Phase 1/2 Trial of RP-L201 for Leukocyte Adhesion Deficiency-I
Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) today announces preliminary data from its Phase 1/2 clinical trial of RP-L201, the Company’s lentiviral vector (LVV)-based gene therapy for the treatment of Leukocyte Adhesion Deficiency-I (LAD-I). LAD-I is a rare immune disorder characterized by low or absent neutrophil CD18 expression, predisposing affected individuals to recurrent and fatal infections in childhood. Data from the first patient treated with RP-L201 demonstrated early evidence of efficacy.
“We believe the preliminary data from this first patient are impressive and demonstrate that RP-L201 has the potential to correct deficient CD18 expression that is the hallmark of LAD-I,” said Jonathan Schwartz, M.D., Chief Medical Officer and Senior Vice President of Rocket. “In LAD-I, stem cells are not believed to be compromised by the underlying disorder. Based on this, and an established RP-L201 treatment process that includes a tailored conditioning regimen, we intend to create a standardized and predictable platform for reversing LAD-I. We believe this treatment approach will enable us to reliably correlate drug product to both early and long-term patient outcomes. We look forward to continued evaluation of this first-in-class gene therapy in the ongoing trial and believe that RP-L201 has the potential to be a favorable therapeutic option for this difficult and frequently fatal disease.”
Initial results from the first pediatric patient treated with RP-L201 demonstrate early evidence of safety and potential efficacy. Analyses of peripheral vector copy number (VCN) and CD18-expressing neutrophils were performed through three months after infusion of RP-L201 to evaluate engraftment and phenotypic correction. The patient exhibited early signs of engraftment with myeloid-lineage VCN levels of 1.5 at three months and CD18 expression of 45%, compared to pre-treatment CD18 expressions of <1%. The patient also displayed visible improvement of multiple disease-related skin lesions after receiving therapy. The drug product VCN was 3.8. No safety or tolerability issues related to RP-L201 administration (or investigational product) have been identified to-date. These data are consistent with Rocket’s preclinical studies, which demonstrated that administration of RP-L201 in murine models resulted in stable engraftment and phenotypic correction with restored neutrophil migration capability.
Donald Kohn, M.D., Professor of Microbiology, Immunology and Molecular Genetics, Pediatrics (Hematology/Oncology), Molecular and Medical Pharmacology, member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and principal investigator of the trial said, “Natural history studies indicate a correlation between higher CD18 expression and survival, with 4% to 10% CD18 expression associated with survival into adulthood. Natural history studies have also demonstrated a devastating mortality rate in children with severe LAD-I, as high as 60-75% by 2 years of age, and very limited survival beyond age 10. For these reasons, we’re encouraged to see preliminary evidence that investigational RP-L201 may lead to an increase in the percent of CD18-expressing neutrophils, suggesting it has potential as a life-changing, life-saving treatment option for these young patients.”
The non-randomized open-label Phase 1/2 study of RP-L201 is designed to evaluate the safety and efficacy of RP-L201 in pediatric patients with severe LAD-I and is expected to enroll nine patients globally. The Phase 1 portion of the trial is expected to enroll two patients and will assess the safety, tolerability and preliminary efficacy of RP-L201. The Phase 2 portion of the trial will evaluate overall survival at several leading U.S. and EU centers. RP-L201 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 Fundación Jiménez Díaz (IIS-FJD). The lentiviral vector was developed in a collaboration between The University College of London (UCL) and CIEMAT. Further information about the clinical program is available here.
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 (less than 2% normal expression) 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 California Institute for Regenerative Medicine (Grant Number CLIN2-11480). The contents of this press release are solely the responsibility of Rocket and do not necessarily represent the official views of CIRM or any other Agency of the State of California.