FDA Grants RP-L201 RMAT Designation for LAD-I

Kinnari Patel, PharmD, MBA

The FDA has granted a regenerative medicine advanced therapy (RMAT) designation to RP-L201 as a potential treatment for patients with leukocyte adhesion deficiency-I (LAD-I), according to a statement from Rocket Pharmaceuticals, the company developing the gene therapy.

The RMAT designation is intended for cell and gene therapies that address serious or life-threatening diseases and is based on promising preliminary evidence. For RP-L201, the designation was based on findings from a phase 1/2 study, which was presented at the 2020 ASH Annual Meeting. In the preliminary data, there was a demonstration of efficacy with RP-L201 in 2 patients with severe LAD-I (CD18+ PMN <2%). In the announcement of the RMAT designation, Rocket also noted that the phase 1/2 study had completed enrollment.

“Receiving RMAT designation and completing phase 1/2 patient enrollment are important steps in advancing our RP-L201 LAD-I program as efficiently and responsibly as possible,” Kinnari Patel, PharmD, MBA, president and chief operating officer of Rocket, said in a statement. “We look forward to maximizing the opportunity for enhanced dialogue with the FDA as we work closely with the agency on potential registration, thanks to the RMAT designation."

RP-L201 consists of autologous CD34+ enriched cells transduced ex vivo with a lentiviral vector to add the ITGB2 gene, which encodes the CD18 receptor (beta 2 integrin subunit). Once manufactured and cryopreserved, the transduced autologous cells are infused into the patient at a dose of at least 2 x 106 total CD34+ cells/kg, following myeloablative conditioning with intravenous busulfan.

Overall, 3 patients were treated in the data announced at ASH, however, follow up data of ≥6 months was only available for 2. Doses ranged from 2.8 x 106 to 4.3 x 106 cells/kg. The children's ages were 9 years, 3 years, and 7 months. Across all 3 patients, the infusions were well-tolerated with no signs of treatment-related serious adverse events (AEs) or other severe AEs.

In the 9-year-old patient, a vector copy number (VCN) of 1.2 copies per genome was seen 12 months' post-infusion, existing skin lesions had resolved, and durable CD18+ PMN expression of approximately 40% were seen, suggested a marked clinical improvement. In the second evaluable patient, who was 3 years old, the 6-month post-RP-L201 CD18+ PMN was 23%. Moreover, the peripheral blood VCN numbers looked similar to the first patient, although the numbers had not yet leveled off.

The estimated full enrollment for the study was 9 patients, according to ClinicalTrials.gov, and adverse events are the phase 1 primary end point. The phase 2 portion is focused on survival following infusion and AEs (NCT03812263). The company anticipates further updates from the trial in the second half of 2021.

"Importantly, completing phase 1/2 patient enrollment against the backdrop of a global pandemic is a testament to our team, collaborators, and the patients participating in the trial. I am grateful to all of them for their unwavering commitment as we seek to address the life-threatening impact of LAD-I on the lives of many infants, young children, and their families," said Patel. "We look forward to sharing data from our LAD-I trial in the second quarter in addition to the remainder of the pipeline throughout 2021.”