Rare Daily Staff

The U.S. Food and Drug Administration has granted Fast Track designation to Regenxbio for RGX-121, its experimental gene therapy for mucopolysaccharidosis type II, also known as Hunter syndrome, a rare lysosomal storage disorder that causes progress damage throughout the body and in many cases cognitive impairment.

MPS II is caused by a deficiency of iduronate 2-sulfatase (IS2), an enzyme that is needed to break down certain carbohydrates in the body. Without this enzyme, waste fragments from these carbohydrates accumulate in cells and damage various organs, causing a range of disease-related signs and symptoms, such as hearing loss, declined cardiac function, obstructive airway disease, enlargement of the liver and spleen and decreased range of motion and mobility. In many cases the central nervous system may also be affected. Roughly two of every three patients with Hunter syndrome are also affected with progressive cognitive decline.

Enzyme replacement therapy is used to treat MPS II, but because it is delivered intravenously, the treatment does not address CNS manifestations of the disease.

Regenxbio is developing RGX-121 as a one-time, direct-to-CNS treatment for MPS II. The gene therapy uses the NAV AAV9 vector encoding for human I2S, the gene that produces the enzyme that is deficient in MPS II.

Treatment with RGX-121 has been shown to restore I2S enzyme activity in animal models of MPS II to levels equivalent to or greater than those in non-affected animals. The extent of CNS correction in animal studies suggests that RGX-121 has the potential to be an important and suitable therapeutic option for MPS II patients.

The FDA Fast Track program is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. Fast Track-designated drugs often qualify for priority review, which expedites the FDA review process.

“Children living with MPS II have limited treatment options, making this Fast Track designation tremendously important,” said Kenneth Mills, president and CEO of Regenxbio. He said the company expects to begin a phase I/II trial of the gene therapy in the coming months.

The multi-center, open-label, multiple-cohort, dose-escalation study in pediatric subjects with MPS II will be in patients with documented evidence of early-stage neurocognitive deficit due to MPS. Approximately six male subjects with MPS II greater than or equal to four months old and less than five years old will be treated in two dose cohorts and will receive a single dose of RGX-121 administered by an injection directly in the cerebrospinal fluid. Patients will receive immunosuppression for the first year after RGX-121 is administered.

The primary purpose of the clinical study is to assess the safety and tolerability of RGX-121 at 24 weeks. The primary endpoint will be a safety assessment. The secondary and exploratory endpoints include the effect of RGX-121 on biomarkers of I2S activity in the cerebrospinal fluid, serum and urine and effect of RGX-121 on neurocognitive deficits, as well as other outcome measures. Following completion of the primary study period, subjects will continue to be assessed for a total of 104 weeks following treatment with RGX-121 and then be asked to participate in a long-term follow-up.

“My family has seen firsthand the unmet needs of children with MPS II,” said Jeanette Henriquez, founder of the Hunter Syndrome Foundation. “As we prepare to recognize International MPS Awareness Day on May 15, we are encouraged to see recognition from the FDA on important research exploring new treatment options for children with MPS II.”

May 2, 2018
Photo:
Kenneth Mills, president and CEO of Regexbio