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High-Cost Therapy Profile: September 2025

Clemidsogene Ianparvovec Intracisternal | Regenxbio / Nippon Shinyaku 

Metabolic-gene therapy
September 22, 2025

Proposed indications 

Mucopolysaccharidosis II (MPS II), also known as Hunter Syndrome 

FDA approval timeline

Feb. 8, 2026 (extended due to longer-term data submission) 

  • Fast Track
  • Priority Review
  • Orphan Drug
  • Rare Pediatric Disease (RPD)
  • Regenerative Medicine Advanced Therapy (RMAT)
  • Seeking Accelerated Approval

Place in therapy 

Clemidsogene lanparvovec (RGX-121) is an adeno-associated virus 9 (AAV9) vector gene therapy designed to deliver the iduronate-2-sulfatase (IDS) gene that encodes the iduronate-2-sulfatase (I2S) enzyme to the central nervous system (CNS). 

  • If approved, RGX-121 will become the first gene therapy to treat MPS II and potentially become a first-line treatment option for some patients with MPS II; it will be a first-in-class one-time gene therapy to treat MPS II in boys ages 4 months up to 5 years old and the second agent approved for MSP II, following idursulfase (Elaprase), an enzyme replacement therapy (ERT) that requires weekly weight-based intravenous (IV) infusions that can last up to 8 hours. 
  • RGX-121 restores the mutated IDS gene and provides a permanent source of secreted I2S protein (structurally identical to normal I2S) across the blood-brain barrier, allowing for long-term cross correction of cells throughout the brain and spinal cord.  
  • RGX-121 will be the first gene therapy used to treat the neurocognitive decline in MPS II and it will potentially address both the neurodevelopmental and systemic effects of MPS II.  
  • RGX-121 demonstrated long-term and sustained reductions in cerebral spinal fluid (CSF) levels of heparan sulfate disaccharide D2S6 (trisulfated disaccharide component of heparan sulfate substrate), which is a key biomarker of brain disease activity in MPS II and a surrogate endpoint that is likely to predict clinical benefit in these patients. 
  • RGX-121 is also being evaluated in a Phase 1/2 study of boys ages 5 years up to 17 years. 
  • If approved, pipeline agent tividenofusp alfa (DNL310), an ERT, will compete with RGX-121. Another pipeline agent is DNL310, an IV fusion protein ERT composed of human I2S that is fused to an enzyme transport vehicle (ETV), engineered to cross the blood-brain barrier (BBB) addressing the CNS symptoms in patients diagnosed with MPS II.

Understanding your data

MPS II is caused by mutations in the IDS gene that controls the production of the I2S enzyme. I2S enzyme is necessary to break down glucosaminoglycans (GAGs) known as large sugar molecules such as heparan sulfate and dermatan sulfate. The deficiency in the IS2 enzyme results in accumulation of GAGs within the cells leading to health problems. RGX-121 is a one-time gene therapy designed to deliver the IDS gene that encodes the I2S enzyme directly addressing the underlying genetic case of MSP II. Clinical trial data on RGX-121 demonstrated long-term sustained reductions in the CSF levels of heparan sulfate D2S6, resulting in long-term systemic effects. Studies evaluating RGX-121 in MPS II include the following: 

  • NCT03566043 CAMPSIITE: A Phase 1/2/3 multicenter, open-label study to evaluate the efficacy, safety, tolerability and pharmacodynamics of RGX-121 in pediatric subjects with MPS II (Hunter Syndrome). 
  • NCT04571970: A Phase 1/2 multicenter, open-label study to evaluate the safety, tolerability and pharmacodynamics of RGX-121 in children 5 years of age and older with MPS II (Hunter Syndrome). 
  • NCT04597385: A long-term follow-up study to evaluate the safety and efficacy of RGX-121. 

Identification of patients would reflect the clinical trials criteria listed in the studies above, as well as diagnosis codes identified from claims data requiring among others: 

Common measurable inclusion criteria: 

  • Diagnosis of MPS II

Common measurable exclusion criteria: 

  • Prior treatment with an AAV-based gene therapy product
  • Received an HSCT

Appendix

Category Procedure codes
MPS II International Classification of Diseases, Tenth Revision (ICD-10): E76.1, E76.3
AAV-based gene therapy products Healthcare Common Procedure Coding System (HCPCS): J3398 (Luxturna), C9032 (Luxturna), J3399 (Zolgensma), J1411 (Hemgenix), J1413 (Elevidys), J1412 (Roctavian), J9029 (Adstiladrin), J1414 (Beqvez), C9172 (Beqvez)
National Drug Code (NDC): 2856060101, 52856060111
HSCT ICD-10: Z94.84, T86.5, M31.11
Current Procedural Terminology (CPT): 38241, 38243, 38205, 38206, 38230, 38240
ICD-10-procedural coding system (PCS): 30230G2,30230G3, 30230Y2, 30230Y3, 30233G2, 30233G3, 30233Y2, 30233Y3, 30240G2, 30240G3, 30240Y2, 30240Y3, 30243G2, 30243G3, 30243Y2, 30243Y3, 30230C0, 30230G0, 30230Y0, 30233G0, 30233C0, 30233Y0, 30240C0, 30240G0, 30240Y0, 30243C0, 30243G0, 30243Y0, 30233Y1, 30243Y1, 30233Y1, 30263Y0, 30263Y1 

Clinical deep dive 

Disease state overview

Mucopolysaccharidosis II, also known as Hunter syndrome, is a rare inherited progressive lysosomal storage disorder that results from deficiency or absence of the lysosomal enzyme, I2S, caused by mutations in the IDS gene. The lack of I2S enzyme results in the accumulation of toxic substances (dermatan sulfate and heparan sulfate) in tissues and organs leading to their dysfunction. Patients can present with either a severe, early-onset type or a less severe, late-onset type. Symptoms can include coarse facial features, a large head, joint stiffness, skeletal abnormalities, respiratory issues, hearing loss, cardiovascular issues and neurological issues (e.g., seizures). Developmental delays become apparent around ages 18 to 24 months. Death due to upper airway disease or cardiovascular failure occurs between 10 to 20 years of age. 

There are two types of MPS II, non-neuronopathic and neuronopathic. The neuronopathic form is more severe and accounts for about two-thirds of cases; it is characterized by cognitive impairment and CNS involvement. The non-neuronopathic form has no neurological symptoms or has less severe symptoms and mental function is usually normal.

Epidemiology 

Mucopolysaccharidosis II usually affects only boys and occurs in about 1 in 100,000 to 1 in 170,000 male births. It has been seen in females on rare occasion. There are about 500 boys diagnosed with Hunter syndrome in the U.S. 

Treatment

There is no cure for MPS II and there is no treatment to address the neurodevelopmental decline. Current treatment includes weekly IV idursulfase (Elaprase), HSCT in younger patients and symptomatic management. Current ERT manages some physical symptoms and slows the progression of disease (reducing liver volume, increasing mobility and reducing respiratory infection frequency) but it does not cross the blood brain barrier and therefore does not impact neurodegeneration associated with MPS II. 

Drug and clinical trial overview 

An open-label, single-arm, two-part, Phase 1/2/3 ongoing dose-escalation study, CAMPSIITE, enrolled boys ages 4 months to 59 months diagnosed with neuronopathic MPS II to evaluate efficacy and safety of RGX-121. Patients were administered a one-time intracisternal gene therapy injection of RGX-121 given at varying doses, 1.3 x 10¹⁰, GC/g brain mass, 2.9 x 10¹¹ GC/g brain mass (pivotal dose) or 6.5 × 10¹⁰ GC/g brain mass. RGX-121 was administered directly into CSF via the subarachnoid cistern (base of the skull).  

In the Phase 1/2 clinical trial (Part 1), 16 patients diagnosed with severe MPS II were enrolled. Patients received the varying doses in three cohorts in addition to receiving IV ERT or they remained ERT naïve. The primary endpoint was safety at 24 weeks. Patients were invited to enroll in the long-term follow-up study. At week 48, CSF heparan sulfate D2S6 levels continued to demonstrate dose-dependent reductions in all three cohorts while 5 patients in Cohort 3 received the pivotal dose and demonstrated CSF heparan sulfate D2S6 levels almost near normal levels.  

In the Phase 3 clinical trial (Part 2) 30 patients were enrolled and patients received the pivotal dose in addition to either receiving IV ERT or remaining ERT naïve. The primary endpoint was CSF GAGs and the co-primary endpoint assessed neurodevelopment with the Bayley and Mullen scores. Interim analysis of data reported that 80% of patients demonstrated significant reductions in CSF levels of D2S6, a key biomarker of brain disease activity, below the maximum attenuated level at 16 weeks. Heparan sulfate D2S6 levels in the CSF demonstrated 85% mean reduction approaching normal levels and were sustained for up to 2 years. Up to four years after treatment, patients exceeded expectations in neurodevelopmental function compared to natural history data.  

Patients who received the pivotal dose demonstrated long-term, sustained reductions in the CSF biomarker. Additionally, most patients (80%) either discontinued IV ERT or remained treatment naïve. RGX-121 was well tolerated with one potentially serious drug-related adverse event (increase in liver enzymes). The most common treatment-related adverse events were vomiting, pyrexia, cough and gastroenteritis.

Pipeline (late-stage development)

Name Manufacturer Route of administration Mechanism of action Proposed / studied indication Status
Tividenofusp alfa (DNL310) AstraZeneca IV a fusion protein ERT (human IDS) MPS II PDUFA 1/5/2026
Pabinafusp alfa (JR-141) JCR Pharmaceuticals IV ERT MPS II Phase 3

The information provided has been developed based on available information as of Sept. 10, 2025. This therapy is NOT FDA approved, and content may change as more information becomes available. Caution should be used when developing formulary and utilization management strategies.

The information contained in this report is intended for educational purposes only and is not intended to define a standard of care or exclusive course of treatment, nor be a substitute for treatment.

All brand names are property of their respective owners. 

References 

  1. ClinicalTrials.gov. NCT03566043 CAMPSITE. A Phase 1/2/3 multicenter, open-label study to evaluate the efficacy, safety, tolerability, and pharmacodynamics of RGX-121 in pediatric subjects with MPS II (Hunter Syndrome). 
  2. ClinicalTrials.gov. NCT04571970. A Phase 1/2 multicenter, open-label study to evaluate the safety, tolerability, and pharmacodynamics of RGX-121 in children 5 years of age and older with MPS II (Hunter Syndrome). 
  3. ClinicalTrials.gov. NCT04597385. A long-term follow-up study to evaluate the safety and efficacy of RGX-121.  
  4. ClinicalTrials.gov. NCT04573023. A Phase 3 study of JR-141 in patients with mucopolysaccharidosis II (STARLIGHT).  
  5. ClinicalTrials.gov. NCT05371613. A Phase 2/3, multicenter, double-blind, randomized study to determine the efficacy and safety of tividenofusp alfa (DNL310) vs idursulfase in pediatric and young adult participants with neuronopathic or non-neuronopathic mucopolysaccharidosis type II.  
  6. Ficicioglu C. RGX-121 gene therapy for the treatment of severe mucopolysaccharidosis Type II (MPS II): CAMPSIITE Phase 1/2/3: A clinical study update. Available at: https://www.regenxbio.com/getmedia/11fe4b70-9e3c-4210-9cff-0532c8ed4eb0/WORLD23-RGX-121-101-PLATFORM-FINAL.pdf?ext=.pdf. Accessed August 22, 2025.   
  7. Giugliani R. CAMPSIITE Phase I/II/III: Interim clinical update of clemidsogene lanparvovec (RGX-121), an investigational gene therapy for treatment of neuronopathic mucopolysaccharidosis type II (MPS II). September 5, 2025. Available at: https://www.regenxbio.com/getmedia/5b470e1c-62f3-429e-94ea-1a4db12e3639/CAMPSIITE-RGX-121-ICIEM-Final-September-2025.pdf?ext=.pdf. Accessed September 12, 2025. 
  8. Harmatz P, Escolar M, Ficicioglu C, et al. RGX-121 gene therapy for severe Mucopolysaccharidosis Type II (MPS II): Interim neurodevelopmental outcomes and biomarker results (4164). Neurology. Volume 96 • Number 15_supplement. April 13, 2021. 
  9. Hulshizer R, Lynch M, De Lurio J, et al. PCORI Health Care Horizon Scanning System Database. Patient-Centered Outcomes Research Institute; Clemidsogene lanparvovec (RGX-121) to treat neuronopathic mucopolysaccharidosis type II; Topic ID: 1149. 2021. Updated 7/3/25. Available at: https://horizonscandb.pcori.org/report/topics/149. Accessed Date: July 23, 2025. 
  10. Hunter syndrome overview. Available at: What is Hunter syndrome | Project Alive. Accessed August 25, 2025. 
  11. Meglio M. FDA grants Priority Review, sets Prescription Drug User Fee Act (PDUFA) Date for Hunter syndrome treatment tividenofusp alfa. July 7, 2025. Available at: https://www.neurologylive.com/view/fda-grants-priority-review-sets-pdufa-date-hunter-syndrome-treatment-tividenofusp-alfa. Accessed September 1, 2025. 
  12. Meglio M. Gene therapy RGX-121 demonstrates promising results in pivotal CAMPSIITE trial of Hunter syndrome. September 13, 2024. Available at: https://www.neurologylive.com/view/gene-therapy-rgx-121-demonstrates-promising-results-pivotal-campsiite-trial-hunter-syndrome. Accessed August 22, 2025. 
  13. Muenzer J, Bodamer O, Burton B, et al. The role of enzyme replacement therapy in severe Hunter syndrome-an expert panel consensus. Eur J Pediatr. 2012 Jan;171(1):181-8. DOI: 10.1007/s00431-011-1606-3. Epub 2011 Oct 29.  
  14. National Library of Medicine. IDS gene iduronate 2-sulfatase. Available at: https://medlineplus.gov/genetics/gene/ids/. Accessed August 20, 2025.   
  15. National Organization for Rare Disorders. Mucopolysaccharidosis Type II. Available at:  https://rarediseases.org/rare-diseases/mucopolysaccharidosis-type-ii-2/. Accessed August 20, 2025.  
  16. REGENXBIO announces positive data from pivotal dose level of RGX-121 demonstrating long-term systemic effect. September 3, 2024. Available at: https://ir.regenxbio.com/news-releases/news-release-details/regenxbio-announces-positive-data-pivotal-dose-level-rgx-121. Accessed August 21, 2025. 
  17. REGENXBIO announces FDA review extension of BLA for RGX-121 to treat patients with MPS II. August 18, 2025. Available at: https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-fda-review-extension-bla-rgx-121-treat. Accessed August 21, 2025.  
  18. REGENXBIO announces closing of strategic partnership with Nippon Shinyaku for MPS diseases. March 4, 2025. Available at: https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-closing-strategic-partnership-nippon/#:~:text=About%20RGX%2D121,from%20the%20European%20Medicines%20Agency. Accessed August 21, 2025. 
  19. REGENXBIO reports second quarter 2025 financial results and operational highlights. August 7, 2025. Available at:  https://ir.regenxbio.com/news-releases/news-release-details/regenxbio-reports-second-quarter-2025-financial-results-and. Accessed August 25, 2025. 
  20. Regenxbio's RGX-121 could become the new standard of care in Hunter syndrome. June 6, 2025. Available at: https://seekingalpha.com/article/4793086-regenxbios-rgx-121-could-become-the-new-standard-of-care-in-hunter-syndrome. Accessed August 25, 2025. 
  21. Scarpa M, Almássy Z, Beck M, et al. Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease. Orphanet J Rare Dis. 2011 Nov 7;6:72. DOI: 10.1186/1750-1172-6-72. 
  22. Scarpa M, Lampe C. Mucopolysaccharidosis Type II. 2007 Nov 6 [Updated 2025 Jan 16]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1274/. Accessed February 2025. 
  23. Shapiro EG, Eisengart JB. The natural history of neurocognition in MPS disorders: A review. Mol Genet Metab. 2021 May;133(1):8-34. DOI: 10.1016/j.ymgme.2021.03.002. Epub 2021 Mar 11. PMID: 33741271.  
  24. Wraith JE, Scarpa M, Beck M, et al. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. 2008 Mar;167(3):267-77. Epub 2007 Nov 23. 
  25. Zhou J, Lin J, Leung WT, Wang L. A basic understanding of mucopolysaccharidosis: Incidence, clinical features, diagnosis, and management. Intractable Rare Dis Res. 2020 Feb;9(1):1-9. DOI: 10.5582/irdr.2020.01011.  
  26. Żuber Z, Kieć-Wilk B, Kałużny Ł, Wierzba J, Tylki-Szymańska A. Diagnosis and management of mucopolysaccharidosis Type II (Hunter Syndrome) in Poland. Biomedicines. 2023 Jun 8;11(6):1668. DOI: 10.3390/biomedicines11061668. 
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