Dismay as FDA blocks Regenxbio's Hunter syndrome therapy
Curran Simpson, Regenxbio's president and CEO.
The FDA has said it needs more information before it can approve Regenxbio's gene therapy for Hunter syndrome, driving the company's share price down 15% after-hours.
In a complete response letter (CRL), the US regulator said it did not agree that multiple data additions sent over by the Rockville, Maryland biotech in support of its marketing application for RGX-121 (clemidsogene lanparvovec) addressed issues with the dossier, which included concerns about the design of the main study submitted in support of the therapy.
Hunter syndrome, also known as mucopolysaccharidosis type II (MPS II), is a rare, X-linked recessive genetic disease caused by a deficiency in the enzyme iduronate-2-sulfatase that can lead to developmental delays, sometimes resulting in severe cognitive and physical problems within the first two years of age.
The news has been greeted with consternation by the National MPS Society in the US, whose president and chief executive, Terri Klein, said she was "extremely disheartened" by the decision.
"Families know the devastating trajectory of this disease all too well and have waited 20 years for new treatment options. They cannot wait any longer," she added.
"Drug development for ultra-rare diseases must be streamlined to allow new medicines to reach patients. We urge the FDA to find a swift path forward so that boys living with MPS II and their families have the chance for a better life."
At the moment, Hunter syndrome patients can be treated with weekly intravenous enzyme replacement therapy (ERT) with Takeda's Elaprase (idursulfase). RGX-121 offered the prospect of a one-shot treatment, however, freeing patients from the need for regular clinic visits by allowing their bodies to produce the defective enzyme directly.
Regenxbio said it had attempted to alleviate the FDA's concerns, which spanned the patient population enrolled in the trial, the comparison with the natural history of MPS II using a historical cohort, and the surrogate marker (cerebrospinal fluid levels of the D2S6 biomarker) used to show the therapy was able to correct the genetic defect.
However, despite "active discussions" during the review process – which was delayed from an earlier action date of 9th November, 2025 – "ultimately, the FDA did not agree the data set provided substantial evidence of effectiveness."
There were also warning signs for the programme in January when the FDA placed a clinical hold on both RGX121 and RGX-111, Regenxbio's gene therapy for Hurler syndrome (MPS I), after a single case of a tumour in a phase 1/2 clinical trial of the latter treatment.
"This decision is devastating for the families of boys living with this progressive, life-threatening disease," said Curran Simpson, Regenxbio's president and CEO, who noted the company has been working on the therapy for more than a decade.
"We are concerned about FDA's feedback regarding the overall development path and evaluation of the data in the context of the urgent need for this irreversible ultra-rare disease," he added.
The company hopes to convene a meeting with the FDA to discuss the CRL and a route to a resubmission of the marketing application for RGX-121 that will include ways to "clarify the neuronopathic patient population" and provide additional long-term follow-up data.
