Regenxbio and Rocket Receive FDA Regenerative Medicine Advanced Therapy Designation for Gene Therapies

Rare Daily Staff

The U.S. Food and Drug Administration granted Regenerative Medicine Advanced Therapy, or RMAT, designation for two gene therapies in development to treat rare diseases, Regenxbio’s RGX-121 for the treatment of Hunter syndrome and Rocket Pharmaceuticals’ RP-L301 for the treatment of pyruvate kinase deficiency.

MPS II, or Hunter syndrome, is a rare, X-linked recessive disease caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase (I2S) leading to an accumulation of glycosaminoglycans (GAGs), including heparan sulfate (HS) in tissues which ultimately results in cell, tissue, and organ dysfunction, including in the central nervous system. In severe forms of the disease, early developmental milestones may be met, but developmental delay is readily apparent by 18 to 24 months. Specific treatment to address the neurological manifestations of MPS II remains a significant unmet medical need.

Regenxbio’s RGX-121 is an investigational one-time AAV therapeutic for the treatment of Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome. Preliminary clinical evidence from RGX-121 indicates its potential to address unmet medical needs for MPS II. RGX-121 is currently being studied in the phase 1/2/3 CAMPSIITE trial that is enrolling MPS II patients ages 4 months to 5 years as part of a pivotal program. in February 2023, REGENXBIO announced additional interim data from the phase 1/2 part of the trial, demonstrating that RGX-121 continued to be well-tolerated across 15 patients. Patients receiving the pivotal program dose level continued to demonstrate the largest reductions in CSF GAGs, including Heparin Sulfate (HS) and HS D2S6, which approached normal levels at 48 weeks. CSF GAGs have the potential to be considered a surrogate biomarker that is reasonably likely to predict clinical benefit in MPS II disease under the accelerated approval pathway, as buildup of GAGs in the CSF of MPS II patients correlates with clinical manifestations, including neurodevelopmental deficits. In addition, improvements in neurodevelopmental and daily activity skill acquisition were observed up to three years after RGX-121 administration.

Established under the 21st Century Cures Act, a drug is eligible for RMAT designation if it is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug or therapy has the potential to address unmet medical needs for such disease or condition. RMAT designation includes the benefits of early FDA interactions to discuss surrogate or intermediate endpoints, potential ways to support accelerated approval and satisfy post-approval requirements, potential priority review of the BLA and other opportunities to expedite development and review. In addition, sponsors of products that have been granted RMAT designation and which received accelerated approval may be able to fulfill the post-approval requirements from clinical evidence obtained from sources other than the traditional confirmatory clinical trials.

“This is an important regulatory milestone, and we remain on track to complete enrollment of CAMPSIITE in the first half of 2023 to support a BLA filing in 2024 using the accelerated approval pathway,” said Steve Pakola, chief medical officer of Regenxbio.

RGX-121 has also received Orphan Drug, Rare Pediatric Disease, Fast Track designations from the FDA.

Rocket Pharmaceuticals’ RP-L301 is a lentiviral-based gene therapy for pyruvate kinase deficiency (PKD), a rare blood disorder characterized by severe anemia and excessive red blood cell breakdown. RMAT designation was granted based on robust safety and efficacy data from the ongoing phase 1 RP-L301 clinical trial and its potential to cure a life-threatening disease for which no curative therapies currently exist.

PKD is a rare, monogenic red blood cell disorder resulting from a mutation in the PKLR gene encoding for the pyruvate kinase enzyme, a key component of the red blood cell glycolytic pathway. Mutations in the PKLR gene result in increased red blood cell destruction and the disorder ranges from mild to life-threatening anemia. PKD has an estimated prevalence of 4,000 to 8,000 patients in the U.S. and Europe. Children are the most commonly and severely affected subgroup of patients. Patients with PKD have a high unmet medical need, as currently available treatments include splenectomy and red blood cell transfusions, which are associated with immune defects and chronic iron overload.

Results from the phase 1 program presented recently at the 26th Annual Meeting of the American Society of Gene and Cell Therapy demonstrate robust and sustained efficacy in both adult patients up to 30 months post-infusion demonstrated by normalized hemoglobin (from baseline levels in the 7.0-7.5 g/dL range), improved hemolysis parameters, red blood cell transfusion independence and improved quality of life with documented improvements via formal quality of life assessments. The safety profile appears highly favorable, with no RP-L301-related serious adverse events in either of the adult patients.

The first pediatric patient results suggest efficacy similar to the adult cohort with an initial greater than five-point increase in hemoglobin (from median baseline level of 7.9 g/dL). The infusion was well tolerated, with engraftment achieved at day +15, hospital discharge less than one month following infusion, and no RP-L301-related serious adverse events or red blood cell transfusion requirements following engraftment.

Rocket anticipates initiating the phase 2 pivotal trial in the fourth quarter of 2023. In addition to RMAT, RP-L301 has also received Fast Track and Orphan Drug designations.

“Receiving RMAT designation from the FDA for RP-L301 is a major achievement in our pursuit to bring the first, potentially curative gene therapy treatment to patients living with PKD who have high unmet need,” said Kinnari Patel, president and chief operating officer of Rocket Pharma. “Further, all four Rocket-sponsored programs with clinical data now have received RMAT designation from the FDA across both platforms, a unique showcase of our team’s ability both to select appropriate targets and develop gene therapies for them.”

Photo: Steve Pakola, chief medical officer of Regenxbio