Gene Therapy for LAD-1 Demonstrates Efficacy


Rocket Pharmaceuticals announced positive data on RP-L201 in leukocyte adhesion deficiency-I, as well as RP-A501 for Danon disease.

RP-L201 has shown preliminary efficacy in treating leukocyte adhesion deficiency-I (LAD-I), according to positive interim data from a phase 1/2 trial (NCT03812263) announced by Rocket Pharmaceuticals.1

The gene therapy has so far been well tolerated and has produced durable CD18 expression and consistent peripheral blood vector copy number (VCN) levels in all patients treated so far, with follow-up times of 3 to 18 months. The data were presented at the 28th Annual Congress of the European Society of Gene & Cell Therapy (ESGCT), October 19-21, 2021. 

“We are excited to share positive data updates from our Phase 1/2 trial for LAD-I and are pleased to report that in each of the initial seven RP-L201 treated patients, CD18 expression has significantly exceeded the 4-10% threshold associated with survival into adulthood, with consistent peripheral blood vector copy number levels,” said Jonathan Schwartz, MD, chief medical officer, Rocket Pharma, in a statement.1

The study plans to enroll 9 participants with severe LAD-I (CD18 expression <2%). Seven patients have been treated to date with a single infusion of RP-L201, which consists of modified CD34+ hematopoietic cells transduced with Chim-CD18-WPRE lentiviral vector. Infusions have been well-tolerated and no serious adverse events (AEs) related to treatment have occurred.

READ MORE: Benefits of RP-L201 in LAD-I Persist With Additional Follow-Up

No patients have required hospitalization for LAD-I—related infections following treatment. In all 7 patients, neutrophil CD18 expression exceeded the 4% to 10% threshold associated with survival into adulthood, contrary to the severe LAD-I phenotype. These improvements were durable, as they were sustained for 3 months (n = 2), 6 months (n = 2), 9 months (n = 2) and 12 months (n = 1) of follow-up. Peripheral VCN levels of 0.5 – 2.5 copy per genome are also stable. 

From shortest to longest follow-up times, patients had sustained CD18 expression in 25.6%, 51.2%, 51.6%, 86.6%, 70.9%, 28.2%, and 43.7% of neutrophils. In the same order, patients had peripheral blood VCN levels of 0.54, 0.79, 1.38, 2.4, 2.49, 0.88, and 1.43 copies per genome. Additionally, the patient with 18 months of follow-up experienced a resolution of their pre-existing skin lesions.

“These positive data continue to support the potential of RP-L201 to yield durable clinical benefit in patients with severe LAD-I and advances our potentially registration-enabling dataset in this fatal disorder and across Rocket’s lentiviral programs at large. We look forward to reporting additional clinical data later in the fourth quarter,” Schwartz added.1

Rocket also recently presented positive data from a phase 1 trial (NCT03882437) of RP-A501, a gene therapy for the potential treatment of Danon disease at the Heart Failure Society of America (HFSA) Annual Scientific Meeting, September 10-13, 2021.2

RP-A501 was well-tolerated, with only transient and reversible AEs. All 3 low-dose (6.7e13 vg/kg) patients had sustained cardiac LAMP2B expression and improvements in the 6-minute walk test (6MWT). Two patients also improved in New York Heart Association class.

“Patients with Danon Disease desperately need a treatment option that provides meaningful therapeutic benefit with a manageable safety profile, and we are excited to be a part of the HFSA Annual Meeting and to share this important work,” Schwartz said in a previous statement.2 “We continue to be encouraged by the safety and durable clinical benefit RP-A501 has demonstrated in the low dose, with one patient now followed to 24 months. Additionally, we are working expeditiously to commence treatment in the low-dose (6.7e13 vg/kg) pediatric patient cohort in the third quarter and expect to provide a comprehensive clinical update from the Phase 1 trial in the fourth quarter.”

1. Rocket Pharmaceuticals announces positive clinical data from RP-L201 trial for the treatment of LAD-I at the 28th Annual Congress of the European Society of Gene & Cell Therapy (ESGCT). News release. Rocket Pharmaceuticals. October 20, 2021.
2. Rocket Pharmaceuticals Presents Clinical Data from RP-A501 Trial in Danon Disease at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2021. News release. Rocket Pharmaceuticals. September 14, 2021.
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