dm+d

Unassigned

New Medicines

Leukocyte adhesion deficiency-1 (LAD-1)

Information

New molecular entity
Rocket Pharmaceuticals
Rocket Pharmaceuticals

Development and Regulatory status

Phase II Clinical Trials
Phase I Clinical Trials
Phase II Clinical Trials
Yes
Yes
Mar 21EMA grants PRIME (PRIority MEdicine) status to RP L201 for treatment of immunodeficiency disorders like LAD-1, on the basis of preliminary safety and efficacy data from the ongoing PI/II trial [3].
Mar 21FDA grants regenerative medicine advanced therapy (RMAT) designation for RP L201 for treatment of immunodeficiency disorders like LAD-1. Also has orphan drug status in US and EU [3].
Apr 20Granted Advanced Therapy Medicinal Product (ATMP) designation by EMA [3].
Dec 18Granted fast track status in US [3].
Nov 18Granted Rare Pediatric Disease status in US [3].

Category

An autologous gene therapy where CD34+ stem cells are taken from the patient and modified genetically ex vivo using a Chim-CD18-WPRE lentiviral vector carrying the therapeutic ITGB2 gene, encoding for the human CD18 receptor. Given as a single dose.
Leukocyte adhesion deficiency (LAD) is a primary immunodeficiency characterized by defects in the leukocyte adhesion process, marked leukocytosis and recurrent infections. Prevalence is unknown, but less than 350 cases have been reported so far [1].
Leukocyte adhesion deficiency-1 (LAD-1)
Intravenous infusion

Trial or other data

Mar 21PI study (NCT03825783) is recruiting [2].
Oct 20PI/II study (NCT03812263) is recruiting [2].
Aug 19PI/II trial to assess the safety and efficacy of RP-L201 in patients with immunodeficiency disorders like LAD-1) starts (RP-L201-0318; NCT03812263). 9 patients aged 3 months and older will be recruited in the US and UK (at Great Ormond Street Hospital). Phase I will assess the therapeutic safety and preliminary efficacy of the infusion of RP L201 in two patients and PII portion of the trial will evaluate overall survival. Collection of primary outcome data is expected to complete Nov 22 [2].
Apr 19PI trial to assess the safety and efficacy of RP L201 in patients with immunodeficiency disorders like LAD-1 starts (RP-L201-0218; NCT03825783). Two patients will be enrolled in Spain. They will undergo mobilization and collection of peripheral blood hematopoietic stem cells (HSCs) with granulocyte-colony stimulating factor (G-CSF) and plerixafor or bone marrow harvest in select circumstances. HSCs will then be transduced with the therapeutic vector (Chim.hCD18-LV), with the intent of enabling stable integration of the provirus in the genome of stem and progenitor cells. If the number of CD34+ cells that are cryopreserved is at least 4×10E6 total CD34+ cells/kg, subjects will receive myeloablative conditioning with intravenous busulfan. The gene-modified CD34+ cells will be then transplanted back into the subject. Once engrafted, it is anticipated that the gene-modified stem and progenitor cells will enable hematopoiesis, generating blood cells in which the integrated therapeutic gene (ITGB2) will be transcribed and translated to produce the therapeutic CD18 protein with a preferential high expression in mature myeloid cells. Leukocytes expressing a functional CD18 will have the capability to arrest on endothelial surfaces and extravasate to infectious sites, enabling a competent antimicrobial response and reversing the clinical disorder. Primary outcomes are safety and survival (as determined by the proportion of subjects alive at age 24 months and at least 1-year post infusion without allogeneic hematopoietic stem cell transplant); collection of these data is due to complete Oct 21 [2].