Infusion rate adjustment in enzyme replacement therapy with pabinafusp alfa for mucopolysaccharidosis II

Infusion rate adjustment in enzyme replacement therapy with pabinafusp alfa for mucopolysaccharidosis II | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 8 October 2025 V1 Latest version Share on Infusion rate adjustment in enzyme replacement therapy with pabinafusp alfa for mucopolysaccharidosis II Authors : Kimitoshi Nakamura , Norio Sakai , Hideaki Hirai , Naoko Takasao , Ryo Ibaraki , Tatsuyoshi Yamamoto , and Yuji Sato 0000-0002-5185-8643 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.175995009.98204591/v1 294 views 179 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Aims Enzyme replacement therapy (ERT) for mucopolysaccharidosis II (MPS II) involves long-term weekly intravenous infusions often lasting over 3 hours each, which burdens paediatric patients and caregivers and can negatively affect their quality of life and treatment compliance. This study’s aim was to determine whether shortening infusion durations affects the long-term efficacy and safety of ERT. Methods A post-hoc pharmacodynamic analysis was conducted using 260-week clinical data on 27 Japanese patients with MPS II who participated in a phase II/III clinical trial and an extension study of pabinafusp alfa administered at a dose of 2.0 mg/kg/week following a switch from prior ERT with idursulfase. Safety was assessed through the incidence of adverse events, side effects, and infusion-associated reactions, and efficacy was evaluated on the basis of heparan sulfate and dermatan sulfate concentrations in the cerebrospinal fluid (CSF), serum, and urine, along with neurocognitive development and liver and spleen volumes. The weekly infusion duration was ≥3 hours until Week 52, after which discretionary shortening was permitted. Results Shorter infusion times did not correlate with increased infusion-associated reactions or other adverse events. Substrate levels in the CSF, serum, and urine, as well as liver and spleen volumes, remained stable irrespective of infusion rates, indicating sustained therapeutic efficacy. Conclusions Infusion rate adjustments did not significantly affect the safety or efficacy of ERT with pabinafusp alfa in patients with MPS II, indicating that clinicians can have flexibility to shorten infusion times as appropriate to improve patients’ quality of life and treatment compliance. Introduction Mucopolysaccharidosis II (MPS II; Hunter syndrome) is a rare lysosomal storage disorder caused by a genetic deficiency of the enzyme iduronate-2-sulfatase (IDS) 1 , which leads to systemic accumulations of substrates, such as heparan sulfate (HS) and dermatan sulfate (DS), resulting in a wide spectrum of somatic and neuropsychiatric symptoms 2,3 . The clinical presentation and prognosis of MPS II vary widely from the severe (neuronopathic or rapidly progressive) phenotype to the attenuated (non-neuronopathic or slowly progressive) phenotype 4 . Patients with the severe phenotype typically present with progressive and severe central nervous system (CNS) involvement in addition to somatic symptoms, while those with the attenuated phenotype primarily exhibit somatic manifestations with little or no CNS involvement. Enzyme replacement therapy (ERT) with weekly infusions of recombinant human IDS (idursulfase) is the current standard of care, but while it relieves the somatic symptoms, it cannot address the CNS symptoms because the blood-brain barrier (BBB) prevents large molecules, including enzymes, from reaching the CNS 5,6 . To address this limitation, pabinafusp alfa (JR-141), a fusion protein of IDS and an anti-human transferrin receptor antibody, was developed to enable BBB penetration so that both the CNS and somatic symptoms can be treated 7-12 . Pabinafusp alfa was approved for clinical use in Japan in 2021 13 , while a global phase III trial is ongoing in the UK, EU and the Americas (NCT04573023). Early initiation of ERT following diagnosis is important to minimize progressive substrate accumulation and resultant systemic organ damage. However, the requirement for long-term weekly intravenous infusions of enzyme products poses significant challenges in paediatric clinical practice. These include difficulties with repeated venipunctures, leakages from intravenous lines, complications with central venous port placement 14 , and the need to manage infusion-associated reactions 15 , which may necessitate slower infusion rates and prolonged infusion times. These issues can lead to frequent extended hospital visits that adversely affect patients’ quality of life and undermine long-term treatment compliance, despite the critical need for sustained ERT to treat this progressive life-threatening disease. To manage infusion-associated reactions, such strategies as reducing infusion rates and adjusting prophylactic medication have been implemented 16 , but concerns remain as to whether modifying infusion parameters affects the pharmacodynamics of the enzyme product, potentially compromising the safety and efficacy of ERT. To investigate whether infusion adjustments affect the pharmacodynamics of pabinafusp alfa, we conducted a post-hoc comparative analysis of long-term data on patients with MPS II who participated in clinical trials of pabinafusp alfa. Methods We conducted a post-hoc pharmacodynamic analysis of 260-week safety and efficacy data on 27 patients with MPS II who had been administered with pabinafusp alfa in a phase II/III trial (JR-141-301 study; NCT03568175) 9 , and in a subsequent extension study (JR-141-302 study; NCT04348136). Both studies were conducted in compliance with the Declaration of Helsinki. The protocols and procedures regarding informed consent were reviewed and approved by the Institutional Review Board at each participating institution. Twenty-four of the patients had previously undergone ERT with IDS and were switched to pabinafusp alfa at 2.0 mg/kg but at different infusion rates, while 3 were newly diagnosed patients whose ERT started with pabinafusp alfa at the same dosage as the switched patients. For the purpose of this analysis, the patients were divided into two groups: those who had received pabinafusp alfa at an infusion rate of > 33 mL/h at least once during the treatment period (Group A, “fast”), and those who had received pabinafusp alfa exclusively at infusion rates of ≤ 33 mL/h (Group B, “slow”). The safety data included the incidence of adverse events, side effects attributed to pabinafusp alfa, infusion-associated reactions, and development of anti-drug antibodies during the 260-week period. Efficacy evaluation was based on three sets of data: 1) concentrations of HS and DS in CSF, serum, and urine, reflecting overall systemic substrate accumulation; 2) liver and spleen volumes as assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI) to identify hepatosplenomegaly, a representative sign of MPS II; 3) neurocognitive development as assessed by the Kyoto Scale of Psychological Development (a standardized battery of tests widely used in Japan and known to correlate well with the Bayley Scales of Infant Development, Third edition) to evaluate CNS involvement. Endpoints 1) and 2) were used to evaluate the somatic/peripheral efficacy of pabinafusp alfa, while endpoint 3) was used to evaluate its efficacy against MPS II-associated neuronopathy. not-yet-known not-yet-known not-yet-known unknown Results Safety analysis Figure 1 shows the average total infusion time over each 6-month period during the 260 weeks of ERT with pabinafusp alfa in the 27 patients. The study protocol of the phase II/III trial stipulated a minimum weekly infusion duration of 3 hours until Week 52, but in the subsequent extension study, the investigators were allowed to shorten infusion times at their discretion. This resulted in a tendency for the weekly infusion times to become shorter as the investigators tried to reduce the burden on the patients. Figure 1 Group A (the “fast” group) was made up of 21 patients who had received one or more infusions at >33 mL/h (i.e. less than 90% of the recommended 3-hour duration), while Group B (the “slow” group) consisted of a smaller number of patients (n = 6) who had received pabinafusp alfa exclusively at infusion rates of ≤33mL/h (i.e. always over 90% of the recommended infusion duration). Infusion rates and safety-related events over each 50-week period are summarised in Table 1. Overall, there were no notable differences in the incidence of adverse safety-related events between the two groups, indicating that the infusion rate had minimal impact on the safety profile of pabinafusp alfa, and that most patients can tolerate faster infusion rates. Table 1 Tables 2 and 3 provide details of the infusion-associated reactions observed in both groups during Weeks 1-52 and Weeks 53-260 of the extension study, respectively. Figure 2 shows the total number of infusions categorised by duration time, juxtaposed with the corresponding number of infusion-associated reactions. To explore this further, the proportion of infusion-associated reactions relative to the number of infusions was calculated for selected time intervals. For instance, at infusion durations of 3–3.5 hours and 1.5–2 hours, the reaction rates were 2.4% (37/1, 563) and 0.4% (6/1, 343), respectively. These results indicate no apparent correlation between shorter infusion times (i.e. faster infusion rates) and an increased incidence of infusion-associated reactions. Table 2 & 3 Figure 2 Efficacy analysis Concentrations of HS and DS, the two major substrates metabolized by IDS, were quantified according to previously published methods17. Figures 3A and 3B show HS and DS levels, respectively, in the CSF of the 27 patients at baseline (Week 1), and at Weeks 26, 53 and 105. In both groups, the HS and DS levels had decreased by Week 26 and remained low through Week 105, demonstrating that the high levels of HS and DS observed at Week 1 had markedly decreased by Week 26, following the administration of pabinafusp alfa, whose efficacy in addressing the CNS symptoms was sustained throughout the long-term treatment. Figure 3 Figure 4 shows the HS and DS concentrations in the serum (4A, 4B) and urine (4C, 4D) over 260 weeks among the 24 patients who had received prior ERT with idursulfase before the switch to pabinafusp alfa. The levels remained consistently low from Week 1 through Week 261, with no notable differences between the two groups. This suggests that the enzyme activity of ERT, as reflected by serum and urinary HS and DS concentrations, was maintained following the switch from idursulfase to pabinafusp alfa. Figure 4 Figure 5 shows liver and spleen volumes over the 260-week period among the 24 switched patients. These were measured by CT and/or MRI and adjusted for body weight to take account of natural organ growth. The volumes remained stable in both groups, indicating no development of hepatosplenomegaly and suggesting preserved somatic efficacy of ERT after the switch from idursulfase to pabinafusp alfa. Figure 5 Neurocognitive development results for all 27 patients (both the switched patients and those naïve to ERT) as assessed by the Kyoto Scale of Psychological Development are shown in Figures 6A (patients with the attenuated [non-neuronopathic] subtype) and 6B (severe [neuronopathic] subtype). In patients with the attenuated subtype, age-equivalent scores generally increased in line with chronological age, indicating improvement of neurocognitive impairment regardless of infusion rates. In patients with the severe subtype, most showed stabilized or slightly declining development, but again, infusion rates did not appear to affect the age-equivalent scores. In patients with both subtypes (attenuated/severe), early initiation of ERT was associated with better neurocognitive development. Figure 6 In summary, neither the safety nor efficacy data revealed any apparent differences with respect to infusion rates, suggesting that the infusion rate has no significant bearing on the pharmacodynamic effects or safety profile of pabinafusp alfa. Discussion This article summarizes the results of a post-hoc pharmacodynamic analysis of long-term clinical data on Japanese patients with MPS II receiving ERT with pabinafusp alfa. The results indicate that most patients can tolerate faster infusion rates and that different infusion rates do not significantly affect the pharmacodynamics of pabinafusp alfa, suggesting in turn that rates can be adjusted in clinical practice without compromising the safety or efficacy of treatment with the drug. This flexibility should allow clinicians to optimise weekly infusion rates to improve long-term treatment compliance in paediatric patients, along with their quality of life. Although the relationships between infusion rates and changes in pharmacokinetics and pharmacodynamics have been previously investigated 18-23 , few studies have focused on long-term ERT in paediatric patient populations. Most previous discussions of infusion rates in children have centered on maximum allowable infusion volumes in infants 24 . ERT for lysosomal storage disorders requires lifelong weekly intravenous infusions, ideally initiated in infancy. In the absence of other forms of treatment, such as gene therapy 25 , discontinuation of ERT usually leads to disease progression with severe and potentially irreversible consequences. Managing infusion-associated hypersensitivity reactions, which are reported to occur in some 30% of patients with MPS II undergoing ERT 26 , is therefore crucial to avoid treatment interruption. Strategies for managing severe hypersensitivity include intensive immune tolerance induction 27,28 , but infusion rate reduction and/or the administration of antihistamines or antipyretics are generally effective for milder reactions. However, prolonged infusion times may negatively affect patients’ quality of life and treatment compliance, and could potentially alter the pharmacokinetic or pharmacodynamic profiles of the enzyme products used for ERT. Our data indicated that infusion-associated reactions occurred independently of infusion rate adjustments, and that infusion rate had no obvious impact on safety or efficacy in patients experiencing such reactions. This suggests that infusion-associated reactions are more closely associated with individual patients’ specific conditions, such as residual enzyme activity or cross-reactive immunological material (CRIM) status 29 , than with infusion rates. Taken together, the results of this study show that infusion rate adjustments can be made flexibly to respond to actual clinical situations without affecting the pharmacodynamics of ERT with pabinafusp alfa. Several limitations must be acknowledged. First, due to the retrospective nature of the study and limited availability of detailed infusion data, this analysis relied on a binary classification of infusion rates (above or below 33mL/h), which may have oversimplified the actual variability of infusion conditions over the 260-week treatment period. A more detailed analysis of the finer differences in infusion rates and corresponding pharmacodynamic parameters would provide deeper insights into the relationship between infusion rates and pharmacodynamic outcomes. Second, due to the practical difficulties involved in frequent pharmacokinetic data sampling in paediatric patient populations, it was not possible to directly assess the effects of different infusion rates and times on plasma drug concentrations. However, a phase I/II study conducted in Japan 8 showed stable plasma concentrations of pabinafusp alfa across a range of doses (0.01, 0.1, 1.0 and 2.0 mg/kg) administered weekly over a 4-week treatment period, with no apparent effect on safety or tolerability. This supports the view that variations in infusion rates of pabinafusp alfa at the same dosage are unlikely to cause any significant changes in pharmacokinetic parameters, including plasma drug concentrations. Third, it is possible that only those patients who tolerated the standard infusion speed well were subsequently exposed to faster infusion rates, which may have led to lower observed incidences of infusion-associated reactions. Thus, there was a potential bias in infusion rate adjustments reflecting individual patients’ variable tolerability to pabinafusp alfa. In conclusion, this study shows that faster infusion rates do not significantly affect the pharmacodynamics of pabinafusp alfa during long-term ERT in patients with MPS II, and that most patients treated with the drug can tolerate shorter infusion times. Our findings support the clinical flexibility to adjust infusion rates according to individual patient needs without compromising safety or efficacy, which should in turn help improve patients’ quality of life and long-term treatment compliance. not-yet-known not-yet-known not-yet-known unknown Author contributions KN (principal investigator) and NS were responsible for acquisition of the data from the patients enrolled in the phase II/III study and its extension study of pabinafusp alfa. RI was responsible for the study conduct and clinical operation. TY planned the post-hoc analysis. HH and NT handled data management and analysis. YS wrote the first manuscript, which all others reviewed and revised, and the final manuscript was approved by all. Acknowledgements The authors thank Pascal Yoshida, Robin LeWinter, Rob Van Maanen, Toshiaki Ikeda and Naoya Oishi of JCR pharmaceuticals for their assistance and suggestions in finalizing the manuscript. The editorial help provided by Timothy Minton of Keio University is also much appreciated. Conflict of interest statement KN has received consulting fees or honorarium from JCR Pharmaceuticals and Orphan Pacific, and research grant from KM Biologics. NS has received consulting fees or honorarium from JCR Pharmaceuticals and Sanofi, and research grant from JCR pharmaceuticals. HH, NT, RI, TY and YS are employees of JCR pharmaceuticals, the intellectual property owner and manufacturer of pabinafusp alfa. not-yet-known not-yet-known not-yet-known unknown Funding information The post-hoc analysis and the clinical trials on which the analysis is based are all funded by JCR pharmaceuticals. Data availability The data used for this study is available from the corresponding author upon reasonable request. N Occur-rence (%) Events N Occur-rence (%) Events N Occur-rence (%) Events N Occur-rence (%) Events N Occur-rence (%) Events Adverse events (AEs) 21 100 278 21 100 163 18 100 118 16 100 118 15 100 132 Serious AEs 3 14.3 3 2 9.5 2 0 0 0 1 6.3 1 2 13.3 4 Side effects* 10 47.6 49 5 23.8 18 6 33.3 8 5 31.3 16 4 26.7 5 Serious side effects 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Infusion-associated reactions 9 42.9 41 5 23.8 17 5 27.8 6 4 25 14 3 20 4 Group B 1 – 53 weeks (n = 6) 53 – 105 weeks (n = 6) 105 – 157 weeks (n = 5) 157 – 209 weeks (n = 5) 209 – 261 weeks (n = 5) N Occur-rence (%) Events N Occur-rence (%) Events N Occur-rence (%) Events N Occur-rence (%) Events N Occur-rence (%) Events Adverse events (AEs) 6 100 57 6 100 38 4 80 41 5 100 34 4 80 31 Serious AEs 2 33.3 5 2 33.3 4 0 0 0 0 0 0 2 40 2 Side effects 5 83.3 10 3 50 4 3 60 7 1 20 1 1 20 1 Serious side effects 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Infusion-associated reactions 5 83.3 10 3 50 4 3 60 7 0 0 0 1 20 1 Table 1. Safety-related events observed in Group A (infusion rate *Side effects refer to adverse events that the investigators considered to be related to pabinafusp alfa. Number of subjects 21 6 Number of subjects with IARs (%) [95%CI] 9 (42.9) [21.8, 66.0] 5 (83.3) [35.9, 99.6] Number of IARs 41 10 Preferred Terms in MedDRA Version 27.0 N (%) 95% CI Events N (%) 95% CI Events Dizziness 1 (4.8) 0.1, 23.8 1 0 (0.0) 0.0, 45.9 0 Headache 1 (4.8) 0.1, 23.8 1 0 (0.0) 0.0, 45.9 0 Syncope 1 (4.8) 0.1, 23.8 1 0 (0.0) 0.0, 45.9 0 Erythema 1 (4.8) 0.1, 23.8 4 0 (0.0) 0.0, 45.9 0 Rash 1 (4.8) 0.1, 23.8 4 0 (0.0) 0.0, 45.9 0 Urticaria 0 (0.0) 0.0, 16.1 0 3 (50.0) 11.8, 88.2 3 Pyrexia 8 (38.1) 18.1, 61.6 26 3 (50.0) 11.8, 88.2 5 Fatigue 1 (4.8) 0.1, 23.8 4 0 (0.0) 0.0, 45.9 0 Chills 0 (0.0) 0.0, 16.1 0 2 (33.3) 4.3, 77.7 2 Table 2. Details of infusion-associated reactions observed during the extension study in Groups A and B in Weeks 1 through 52 IAR: stands for infusion-associated reaction, which is defined in the protocol as reactions harmful to the living body caused by an infusion (e.g. fever, nausea, high blood pressure). Number of subjects 21 6 Number of subjects with IARs (%) [95%CI] 8 (38.1) [18.1, 61.6] 3 (50.0) [11.8, 88.2] Number of IARs 41 12 Preferred Terms in MedDRA Version 27.0 N (%) 95% CI Events N (%) 95% CI Events Seizure 1 (4.8) 0.1, 23.8 1 0 (0.0) 0.0, 45.9 0 Orthostatic intolerance 1 (4.8) 0.1, 23.8 1 0 (0.0) 0.0, 45.9 0 Conjunctival hyperaemia 1 (4.8) 0.1, 23.8 1 0 (0.0) 0.0, 45.9 0 Abdominal pain 1 (4.8) 0.1, 23.8 3 0 (0.0) 0.0, 45.9 0 Diarrhoea 1 (4.8) 0.1, 23.8 1 0 (0.0) 0.0, 45.9 0 Erythema 1 (4.8) 0.1, 23.8 1 0 (0.0) 0.0, 45.9 0 Rash 1 (4.8) 0.1, 23.8 10 2 (33.3) 4.3, 77.7 2 Urticaria 1 (4.8) 0.1, 23.8 14 1 (16.7) 0.4, 64.1 5 Pyrexia 5 (23.8) 8.2, 47.2 9 2 (33.3) 4.3, 77.7 5 Table 3. Details of infusion-associated reactions observed during the extension study in Groups A and B in Weeks 53 through 260 not-yet-known not-yet-known not-yet-known unknown Figure legends (figures are submitted in separate files) Figure 1. Average total infusion time over each 50-week period from Week 1 through Week 261 of ERT with pabinafusp alfa X represents the mean infusion time during the respective weeks. Figure 2. Total number of infusions classified according to the duration of each one (blue bars), and the number of infusion-associated reactions that arose during each infusion (red bars) IAR occurrence rates (actual number of observed IARs / number of infusions) for infusion durations of 0-1.0 h, 1.0-1.5 h, 1.5-2.0 h, 2.0-2.5 h, 2.5-3.0 h, 3.0-3.5 h, 3.5-4.0 h, and over 4 h were 0.0%, 3.7%, 0.4%, 0.6%, 1.9%, 2.4%, 1.6%, and 1.7%, respectively. A total of 5,765 completed infusions were included in this analysis. Nine infusions were discontinued due to various causes, including 19 IARs, and were excluded from analysis. Figure 3. Concentrations of heparan sulfate (HS; 3A) and dermatan sulfate (DS; 3B) in the cerebrospinal fluid (CSF) at Week 1 (baseline), and at Weeks 26, 53, and 105 CSF samples were collected from 21 subjects in Group A (administered with pabinafusp alfa at an infusion rate of >33 mL/h) in Week 1, and from 21, 16, and 18 subjects in Weeks 26, 53, and 105, respectively. The corresponding figures for Group B subjects (pabinafusp alfa at infusion rates ≤ 33 mL/h) were 6 in Week 1, and 6, 6, and 4 in Weeks 26, 53, and 105, respectively. The error bars represent standard deviations. Figure 4. Concentrations of heparan sulfate (HS) and dermatan sulfate (DS) in the serum (4A, 4B) and urine (4C, 4D) at Week 1 (baseline), and at Weeks 26, 53, and 105 Data were available for 19 of the subjects in Group A in Week 1, and for 19, 19, 16, 14, 13, and 13 in Weeks 26, 53, 105, 157, 209, and 261, respectively. The corresponding figures for Group B subjects were 5 in Week 1, and 5, 5, 4, 4, 4, and 3 in Weeks 26, 53, 105, 157, 209, and 261, respectively. The error bars represent standard deviations. Figure 5. Liver and spleen volumes as measured by computed tomography and adjusted for body weight Data were available for 19 of the subjects in Group A in Week 1, and for 19, 19, 19, 16, 14, 13, and 13 in Weeks 26, 53, 105, 157, 209, and 261, respectively. The corresponding figures for Group B were 5 in Week 1, and 5, 5, 4, 4, 4, and 3 in Weeks 26, 53, 105, 157, 209, and 261, respectively. The error bars represent standard deviations. Figure 6. 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Aug 2011;13(8):729-36. doi:10.1097/GIM.0b013e3182174703 Supplementary Material File (figure 1.docx) Download 59.62 KB File (figure 2.docx) Download 56.46 KB File (figure 3.docx) Download 104.16 KB File (figure 4.docx) Download 207.50 KB File (figure 5.docx) Download 74.56 KB File (figure 6.docx) Download 171.01 KB Information & Authors Information Version history V1 Version 1 08 October 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Kimitoshi Nakamura Kumamoto Daigaku Daigakuin Seimei Kagaku Kenkyubu View all articles by this author Norio Sakai Iseikai Kokusai Sogo Byoin View all articles by this author Hideaki Hirai JCR Pharma Kabushiki Kaisha View all articles by this author Naoko Takasao JCR Pharma Kabushiki Kaisha View all articles by this author Ryo Ibaraki JCR Pharma Kabushiki Kaisha View all articles by this author Tatsuyoshi Yamamoto JCR Pharma Kabushiki Kaisha View all articles by this author Yuji Sato 0000-0002-5185-8643 [email protected] JCR Pharma Kabushiki Kaisha View all articles by this author Metrics & Citations Metrics Article Usage 294 views 179 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Kimitoshi Nakamura, Norio Sakai, Hideaki Hirai, et al. Infusion rate adjustment in enzyme replacement therapy with pabinafusp alfa for mucopolysaccharidosis II. Authorea . 08 October 2025. 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