Clemidsogene lanparvovec

Regenxbio intends to provide more evidence and clinical data, aiming to resubmit as soon as possible. Credit: Gorodenkoff / Shutterstock.com. REGENXBIO has received a complete response letter (CRL) from the US Food and Drug Administration (FDA) related to its biologics licence application (BLA) for RGX-121 (clemidsogene lanparvovec) to treat mucopolysaccharidosis II (MPS II), also called Hunter syndrome. The FDA accepted the gene therapy’s application under the accelerated approval pathway in May 2025. The CRL indicated that the FDA agreed in principle with the study protocol and cited several reasons for not granting approval at this stage. Issues addressed included uncertainty over study eligibility criteria used to define neuronopathic versus attenuated disease populations, comparability of the natural history external control data to the study population, and whether cerebrospinal fluid heparan sulphate D2S6 (CSF HS D2S6) is an appropriate surrogate endpoint likely to predict clinical benefit. The FDA outlined several potential ways forward in the CRL, which included conducting a new study, treating additional patients with extended follow-up, or incorporating an untreated control arm, each option presenting significant challenges given the ultra-rare nature of MPS II. During ongoing discussions throughout the BLA process, REGENXBIO believed it had provided sufficient responses and additional data to address points raised by the FDA. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence Independent global MPS and biomarker experts also reviewed and analysed data with the FDA. However, the agency concluded that substantial evidence of effectiveness was not demonstrated by current data to support approval. REGENXBIO plans to request a Type A meeting with the FDA to discuss the CRL and its planned resubmission of the application. The company intends to provide more evidence from global MPS II experts and additional longer-term clinical data to further clarify patient populations and demonstrate effectiveness, aiming to resubmit as soon as possible. REGENXBIO president and CEO Curran Simpson said: “This decision is devastating for the families of boys living with this progressive, life-threatening disease. We are concerned about the 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. “We remain confident in the quality and volume of evidence demonstrating the long-term potential of RGX-121 to positively change the trajectory of Hunter syndrome. This programme has been in development for over ten years.” In January 2025, REGENXBIO entered a strategic collaboration worth $810m with Japan-based Nippon Shinyaku to advance gene therapies targeting the rare MPS. Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free eBook Navigating cell therapy process development The cell therapy manufacturing sector is rapidly evolving, driven by the need to balance innovative process development with rigorous GMP standards. This eBook, brought to you by industry leaders Cytiva, explores how biotech firms can address common challenges — including minimizing contamination risks from manual processes, overcoming resource limitations, and creating scalable, robust designs. Industry experts discuss strategies including automation, strategic outsourcing, and flexible equipment selection to streamline processes and reduce regulatory risks. To unlock expert insights on optimizing your cell therapy pathway from clinical development to commercialization, fill in your details now. Thank you. You will receive an email shortly. Please check your inbox to download the eBook. By Cytiva Thematic You have a right to withdraw your consent at any time, by clicking here . We may still continue to send you service-related and other non-promotional communications. For more information relating to our privacy practices, we invite you to review our privacy policy .

iStock, Nuthawut Somsuk The FDA recommended that REGENXBIO run a new study, treat more patients and include a placebo arm to support a resubmission for the gene therapy RGX-121. After waiting through a three-month delay , REGENXBIO’s investigational gene therapy RGX-121 has been rejected by the FDA for the treatment of Hunter syndrome, an ultra-rare neurodegenerative condition. In a complete response letter (CRL), the regulator cited “uncertainty” over the eligibility criteria that REGENXBIO used for the study included in RGX-121’s data package. The agency also questioned the applicability of using natural history external controls and the validity of the surrogate endpoint—cerebrospinal fluid levels of the biomarker DS26—as basis for approval. For a resubmission, the FDA recommended running a new study, adding more patients, following them for longer periods and using an untreated comparator group. REGENXBIO, however, called these options “challenging” in a Monday release , given the ultra-rare nature of Hunter syndrome. RGX-121 had been accepted into the FDA’s accelerated approval program in May 2025. “The CRL indicates the FDA is clearly being cautious on granting accelerated approvals without placebo-controlled data,” William Blair told investors in a Monday note. In turn, this could pose a regulatory risk for Denali Therapeutics, which is also awaiting the agency’s verdict on the Hunter syndrome therapy tividenofusp alfa, for which a target action date has been set for April 5. While Denali did not rely on natural history comparators to establish the efficacy of its therapy, the study also did not have a placebo arm. Regenxbio is trading at $9.05 before the opening bell on Tuesday, down 12% from its previous closing price of $10.31. The FDA had previously agreed to REGENXBIO’s protocol, the biotech said on Monday, adding that throughout the application process, the biotech had “addressed the points raised in the CRL” by submitting additional data and complying with the regulator’s information requests. CEO Curran Simpson called the rejection “devastating for the families of boys living with” Hunter syndrome. The biotech will seek a Type A meeting with the FDA to discuss not just the path forward for RGX-121 but also to “provide additional evidence” from experts to support the effectiveness of the gene therapy. To support the approval application for RGX-121, REGENXBIO filed data from the Phase 1/2/3 CAMPSIITE study, which in February 2024 demonstrated that at 16 weeks, the gene therapy elicited 86% decrease in DS26, a key disease biomarker, in the cerebrospinal fluid of treated patients. CAMPSIITE enrolled 48 boys aged 4 months to 5 years of age with Hunter syndrome. At the time of the readout, 80% of patients treated with the pivotal dose of RGX-121 were able to discontinue or stay naïve of enzyme replacement therapy. Hunter syndrome affects around 500 boys in the U.S. The disease is caused by mutations to the iduronate-2-sulfatase ( IDS ) gene, rendering its corresponding enzyme defective and leading to a toxic buildup of waste inside cells across the body. REGENXBIO’s RGX-121 counters this mechanism by delivering a functioning copy of the IDS gene.