From The Editor | May 31, 2022

Rocket Pharma's Phase 2 For RP-L201


By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1


Rocket Pharma’s new positive long-term data from its Phase 1/2 trial of lentiviral-based gene therapy RP-L201 for the treatment of Leukocyte Adhesion Deficiency-I (LAD-I). RP-L201 is being developed for LAD-I, a rare genetic immune disorder that predisposes patients to recurrent and fatal infections, often resulting in death within the first two years of life.

The Phase 2 portion of the clinical trial for RP-L201 is currently underway. The Phase 1/2 trial aims to enroll 9 patients is designed to assess the therapeutic safety and efficacy in pediatric patients with severe LAD-I. The primary endpoint in the Phase 2 study is overall survival. The investigational gene therapy works by first collecting blood stem cells from a patient.  These stem cells are then genetically modified to introduce a correct copy of the ITGB2 gene using a virus that has been changed in the laboratory, so that the virus cannot grow, spread, or cause an infection. The genetically modified stem cells are returned to the patient after the patient receives a type of chemotherapy medication called busulfan to remove existing bone marrow cells in order to make room for the genetically modified stem cells to grow. Patients with severe LAD-I who are at least 3 months old and who do not have an available HLA-matched sibling donor for bone marrow transplant are eligible to participate in the clinical trial.

“RP-L201 is Rocket’s ex-vivo lentiviral gene therapy candidate for severe LAD-I,” says Gaurav Shah, M.D., CEO, Rocket Pharma. “This program is near and dear to our hearts at Rocket because leukocyte adhesion deficiency-I is one of the most aggressive and highly fatal immunodeficiencies ever characterized. In fact, two-thirds of these patients unfortunately don’t live past the age of two.

Dr. Shah explains that the top-line data presented at ASGCT last week from the company’s Phase 2 pivotal study showed that all nine patients who received RP-L201 sustained restoration and expression of a protein called CD18. This protein is important in LAD-I because its absence prevents neutrophils from fighting infection, which leads to recurrent pneumonia, fungal infections, hospitalizations, and death.

 “CD18 levels of even 4% can be predictive of long-term lifespan. In our Phase 2 pivotal study, all nine patients sustained CD18 expression, with a median of 56%, at three to 24 months of follow-up,” says Dr. Shah. “All of the patients showed clinical reversal of disease course, including decreases in hospitalizations and severe infections. The top-line Phase 2 pivotal data represents a key milestone for Rocket, as we anticipate regulatory filings in the first half of 2023, but also helps elevate the class of lentiviral-based gene therapies being researched today. Most importantly, these top-line safety and efficacy data point to the potential of RP-L201 to change the treatment paradigm for patients living with severe LAD-I.”

Episode 20 of Cell & Gene: The Podcast features Dr. Shah, and during our conversation, he offers his take on why gene therapy developers have been plagued by clinical holds, whether the FDA’s AAV-focused CTGTAC meeting's takeaways will hold up throughout 2022, and more.