Hunter Syndrome Gene Therapy Stalls... GC Green Cross's Hunterase Presence Grows

FDA Requests Additional Data for Regenxbio's RGX-121 Approval
"Insufficient Evidence of Clinical Benefit" Delays Gene Therapy Commercialization
Hunterase Expected to Benefit Amid Continued Dominance of Enzyme Replacement Therapy

The world's first gene therapy for Hunter syndrome aiming for commercial use has failed to clear the hurdle set by U.S. health authorities, increasing the likelihood that the current competition structure centered on enzyme replacement therapy (ERT) will continue for the time being. As the commercialization of the gene therapy, which had been expected to prevent even cognitive decline in the brain unlike existing treatments, is delayed, some analysts say that GC Green Cross will maintain its advantage with its Hunter syndrome treatment.

Product image of Green Cross's Hunter syndrome treatment 'Heonteoraje'. Green Cross

According to the industry on February 11, the U.S. Food and Drug Administration (FDA) recently issued a Complete Response Letter (CRL) requesting additional information for RGX-121, a Hunter syndrome gene therapy developed by U.S. biotech company Regenxbio. The FDA stated that, based on the submitted clinical trial data alone, it is difficult to determine that there is a real clinical benefit for patients. It pointed out that the patient population was not clearly defined and also raised concerns about the reliability of the trial design, which used a natural history control group instead of a placebo control group. The agency also concluded that the biomarker presented as evidence of treatment effect does not provide sufficient grounds to be accepted as a clinical surrogate endpoint.

RGX-121 is a therapy that delivers a gene so that the deficient enzyme in the body is continuously produced with just a single administration. Because it can overcome the structural limitations of existing enzyme replacement therapy, which requires repeated lifelong dosing for patients, the market had regarded it as a candidate that could change the existing treatment paradigm if commercialized. Its competitiveness over existing therapies was highlighted in particular as the possibility of improving central nervous system symptoms was raised.

With the entry of gene therapy into the North American market delayed, the Hunter syndrome treatment landscape is expected to remain centered on enzyme replacement therapy (ERT) products for the time being. Currently, ERT accounts for more than about 80% of the global Hunter syndrome treatment market.

Against this backdrop, expectations are emerging that Hunterase by GC Green Cross, which is leading the ERT market along with Elaprase by Takeda Pharmaceutical Company, could enjoy a windfall. Hunterase is an intravenously administered ERT treatment. Recently, an intraventricular (ICV) formulation targeting improvement of central nervous system symptoms has also been developed and approved in countries including Japan. In 2025, its sales reached 74.4 billion won, up about 20% from the previous year, solidifying its position as one of GC Green Cross's flagship profit drivers.

The possibility that gene therapies will enter the Hunter syndrome market remains open. In its latest decision, the U.S. Food and Drug Administration (FDA) did not explicitly cite safety concerns as a direct reason for rejecting approval. Although the clinical trial of RGX-111, a gene therapy candidate for Hurler syndrome and a counterpart to RGX-121, was halted due to a brain tumor case during the trial, it is understood that the FDA did not present this issue as a direct reason for refusing approval of RGX-121. Regenxbio has also stated that it plans to secure additional data and resubmit RGX-121.

Industry observers believe that, for gene therapies targeting rare diseases, regulatory authorities are raising the bar for clinical trial design and proof of efficacy. Some predict that it will take a considerable amount of time before such products reach actual commercialization. An industry official said, "Recently, the FDA has been shifting away from accelerated approvals based on biomarkers and is instead demanding rigorous efficacy data that prove actual improvement in patients' lives," adding, "If the sophistication of clinical trial design is not ensured, even an innovative new drug will likely require a long period of time before it can be commercialized."

This content was produced with the assistance of AI translation services.