The Food and Drug Administration rejected Regenxbio’s gene therapy, RGX-121, for the treatment of Hunter syndrome on February 9, 2026, the company announced Monday. The decision represents a setback for the biotechnology firm and the broader field of gene therapy development, coming after the agency halted testing of the treatment due to safety concerns earlier in the month.
According to a complete response letter issued by the FDA, the rejection stemmed from concerns regarding the study’s population, controls and the use of surrogate markers to measure efficacy. Even as the agency indicated it “agreed in principle” to Regenxbio’s proposed study protocol, it consistently voiced concerns throughout the development program regarding its design, according to documents released Monday.
A key issue identified by the FDA was the “heterogeneity” of the patient population enrolled in the pivotal study. Regenxbio had sought a broad label for RGX-121, intending it to be applicable to patients with varying degrees of disease severity. However, the FDA determined the study sample included individuals with an “uncertain phenotype,” raising doubts about whether the participants accurately represented the target population.
The FDA also took issue with Regenxbio’s reliance on external controls, stating they “lack the comparability” with the trial patients. The agency indicated that a resubmission should provide evidence of normalized or improved biomarker levels or neurodevelopmental outcomes. The regulator suggested several potential paths forward, including conducting a new trial, utilizing an untreated control group, or expanding the study to include more patients with longer follow-up periods, but Regenxbio acknowledged that each of these options would present significant challenges given the rarity of Hunter syndrome.
The rejection follows a recent trend of regulatory hurdles for gene therapy developers in the United States. UniQure is currently navigating a similar situation with its Huntington’s disease gene therapy, AMT-130, after FDA Commissioner Marty Makary publicly questioned the therapy’s efficacy. The FDA has requested a sham surgery-controlled study before considering approval of AMT-130.
Regenxbio stated it will request a meeting with the FDA to discuss the complete response letter and explore potential pathways for resubmission. The company did not provide a timeline for when it expects to meet with the agency.
