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Background Imiglucerase (Cerezyme; Sanofi, Paris, France), an analogue of β‐glucocerebrosidase produced by recombinant DNA technology, has been a safe and effective treatment for Gaucher disease (GD) for over 25 years. A new imiglucerase, Abcertin (Seongnam‐si, Gyeonggi‐do, Republic of Korea) has shown a similar safety and efficacy profile in previous clinical studies. This study compared the pharmacokinetics, immunogenicity, safety, and tolerability to EU‐sourced Cerezyme following a single 60 IU/kg dose. Methods This phase 1, single‐center, randomized, double‐blind, two‐way crossover study enrolled 36 healthy volunteers aged 18–45 years. Participants were randomly assigned to receive either Abcertin or Cerezyme in a predetermined sequence. Results Abcertin reached peak plasma concentrations at a median tmax of 61 min (range: 40–121 min). The mean Cmax, AUC0–last, and AUC0–inf were 115.4 mU/mL, 12,190 min·mU/mL, and 12,210 min mU/mL, respectively, indicating bioequivalence to Cerezyme. The mean t½, CL, and Vz were 6.88 min, 376.7 mL/min, and 3.62 L, respectively, and were comparable between the two treatments. One participant in the Cerezyme group developed anti‐drug antibodies, which were non‐neutralizing A total of 24 subjects experienced treatment‐emergent adverse event (TEAE). The most common TEAE was headache (3 in the Abcertin group and 5 in the Cerezyme group), followed by general disorders and administration site condition (3 in Abcertin group and 5 in Cerezyme group). Two participants in the Cerezyme sequence experienced severe TEAEs: one had a urinary tract infection, and the other developed urticaria, which leading to study withdrawal. Conclusion Abcertin demonstrated pharmacokinetic equivalence to Cerezyme, with a comparable safety, immunogenicity, and tolerability profile. These findings support its potential as an affordable biosimilar for GD treatment. This study evaluates the pharmacokinetic equivalence, immunogenicity, and safety profiles of Abcertin and Cerezyme in healthy volunteers. It demonstrated the pharmacokinetic bioequivalence of Abcertin to Cerezyme, highlighted favorable safety and tolerability profiles with no clinically significant adverse events for Abcertin, and confirmed its low immunogenic potential.

Gaucher disease is a progressive lysosomal storage disorder caused by the deficiency of glucocerebrosidase leading to the dysfunction in multiple organ systems. Intravenous enzyme replacement is the accepted standard of treatment. In the current report, we evaluate the safety and pharmacokinetics of a novel human recombinant glucocerebrosidase enzyme expressed in transformed plant cells (prGCD), administered to primates and human subjects. Short term (28 days) and long term (9 months) repeated injections with a standard dose of 60 Units/kg and a high dose of 300 Units/kg were administered to monkeys (n = 4/sex/dose). Neither clinical drug-related adverse effects nor neutralizing antibodies were detected in the animals. In a phase I clinical trial, six healthy volunteers were treated by intravenous infusions with escalating single doses of prGCD. Doses of up to 60 Units/kg were administered at weekly intervals. prGCD infusions were very well tolerated. Anti-prGCD antibodies were not detected. The pharmacokinetic profile of the prGCD revealed a prolonged half-life compared to imiglucerase, the commercial enzyme that is manufactured in a costly mammalian cell system. These studies demonstrate the safety and lack of immunogenicity of prGCD. Following these encouraging results, a pivotal phase III clinical trial for prGCD was FDA approved and is currently ongoing. ClinicalTrials.gov NCT00258778.

Background Fabry disease and Gaucher disease are rare genetic disorders characterized by defective degradation of glycosphingolipids caused by enzymatic deficiencies in α–galactosidase A and β–glucocerebrosidase, respectively, and often require life-long treatment. Treatment options for these disorders include replacing the deficient enzymes via enzyme replacement therapy (ERT). Agalsidase alfa for Fabry disease and velaglucerase alfa for Gaucher disease are two ERT options with demonstrated efficacy, safety, and tolerability. ERT infusions administered by a health care provider (HCP) in the clinic/hospital, or at the patient’s home are considered HCP-supported infusions. Self-administration of ERT (by patient, partner, relative, or caregiver) is optional in patients who tolerate the HCP-supported infusions at home and have a suitable home environment. This analysis explored the safety profiles of self-administered agalsidase alfa (202 patients) and velaglucerase alfa (30 patients) versus HCP-supported infusions using data from the Fabry Outcome Survey (FOS) and Gaucher Outcome Survey (GOS) registries. Results The frequency of infusion-related reactions (IRRs) adverse events (AEs) recorded in the two registries was lower in patients self-administering (FOS: 4.5%, GOS: 0%) versus patients receiving HCP-supported infusions (FOS: 13.6%, GOS: 1.6%). In the FOS registry, AE rates per 100 patient-years (100PY) of follow-up were similar between the self-administration (7.99) and HCP-supported infusion (6.78) groups. In patients self-administering agalsidase alfa, cardiac disorders were the most frequently reported AEs (19 [9.4%] patients) and serious AEs (12 [5.9%]) and gastrointestinal disorders were the most frequently reported IRRs (3 [1.5%]). In the GOS registry, AE rates per 100PY were similar between self-administration (4.97) and HCP-supported infusion (4.67) groups. In patients self-administering velaglucerase alfa, skin and subcutaneous disorders (4 [13.3%]) and infections and infestations (2 [6.7%]) were the most reported AEs and serious AEs, respectively, and no IRRs were reported. Conclusions These findings suggest that self-administration of agalsidase alfa or velaglucerase alfa infusions are not associated with additional safety risks compared with HCP-supported infusions and are a suitable option for qualifying patients. Further research is warranted to support these findings and to explore further the long-term safety and efficacy of ERT self-administration. FOS trial registration: ClinicalTrials.gov, NCT03289065. Registered 01 April 2001, https://clinicaltrials.gov/study/NCT03289065 . GOS trial registration: ClinicalTrials.gov, NCT03291223. Registered 27 July 2010, https://classic.clinicaltrials.gov/ct2/show/NCT03291223 .

Objective This study aims to evaluate the adverse drug reactions associated with imiglucerase in the treatment of Gaucher disease by analyzing data from the FDA Adverse Event Reporting System (FAERS) database. Methods A comprehensive analysis was conducted on 166,800,135 adverse event reports from the FAERS database, covering the period from the first quarter of 2004 to the fourth quarter of 2023. The data were processed using R software and analyzed using multiple disproportionality methods, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS). These methodologies were applied to identify significant adverse reaction signals across various System Organ Classes (SOCs) and Preferred Terms (PTs). Results The analysis revealed significant adverse reaction signals in multiple SOCs, including general disorders and administration site conditions, injury, poisoning and procedural complications, infections and infestations, and nervous system disorders. Notably, general disorders and injury-related conditions had the highest number of reports. At the PT level, the term \"Gaucher disease\" yielded the highest statistical signal. This was identified as a critical reporting artifact, likely representing perceived treatment failure or disease progression, rather than a true adverse reaction. After accounting for this artifact, other significant adverse event signals included increased chitotriosidase, elevated acid phosphatase, and bone infarction, with musculoskeletal and connective tissue disorders being a key area of concern. A comparative analysis against other Gaucher therapies suggests this strong skeletal signal likely reflects confounding by indication rather than a drug-specific risk. Conclusion The findings underscore the importance of ongoing pharmacovigilance to monitor the safety of imiglucerase, especially among vulnerable populations such as pregnant women, long-term users, and those with comorbid hepatobiliary or skeletal conditions.

Background Gaucher disease (GD) is caused by reduced lysosomal enzyme β-glucocerebrosidase activity. Heterogeneous genotypes and phenotypes have been observed within GD types and across ethnicities. Enzyme replacement therapy is generally recommended for patients with type 1 GD, the least severe form of GD. In Japan, velaglucerase alfa has a broad indication covering type 1, 2 or 3 GD.  Methods All patients with type 1, 2, or 3 GD administered velaglucerase alfa 60 U/kg every 2 weeks via intravenous infusion after its launch date in Japan in 2014, were enrolled in a non-interventional, observational post-marketing surveillance (PMS). Individual patient data were reported via case report forms (CRFs). Key safety endpoints investigated included the incidence of infusion-related reactions (IRRs), the safety of velaglucerase alfa in patients with types 2 and 3 GD, from patients under one year of age to elderly patients (≥ 65 years of age). Long-term efficacy was also assessed.  Results In total, 53 patients with GD were registered. CRFs were available for 41 (77.4%) patients at the 6-year interim analysis. Fourteen adverse drug reactions (ADRs) were reported in seven patients. All reported ADRs occurred in patients with type 2 GD. ADRs were reported by 63.6% (7/11) of patients with type 2 GD. Ten ADRs were reported in five patients aged < 4 years. No elderly patients experienced any ADR during the surveillance period. Five ADRs occurring in three (10.0%) patients were classified as IRRs, with one case of vomiting (moderate severity) resulting in treatment discontinuation. Ten serious adverse events were reported in five (16.7%) patients. Three fatal events were considered to be unrelated to treatment with velaglucerase alfa. Platelet counts increased after the administration of velaglucerase alfa and were generally maintained within the normal range over the administration period. Among eleven patients tested for neutralizing anti-velaglucerase alfa antibodies, two (18.2%) were assessed as positive results.  Conclusion PMS data from patients with types 1–3 GD in Japan indicate that long-term treatment with velaglucerase alfa was well-tolerated and associated with increased platelet counts, which is consistent with observations made in studies outside of Japan. Trial registration : NCT03625882 registered July 2014.

Background Limited real-world data from routine clinical care are available on the safety and effectiveness of treatment with taliglucerase alfa in patients with Gaucher disease (GD). Methods Taliglucerase Alfa Surveillance (TALIAS), a multinational prospective Drug Registry of patients with GD, was established to evaluate the long-term safety (primary objective) and effectiveness (secondary objective) of taliglucerase alfa. We present an interim analysis of the data from the Drug Registry collected over the 5-year period from September 2013 to January 2019. Results A total of 106 patients with GD (15.1% children aged < 18 years; 53.8% females) treated with taliglucerase alfa have been enrolled in the Drug Registry, as of January 7, 2019. The median duration of follow-up was 795 days with quartiles (Q1, Q3) of 567 and 994 days. Fifty-three patients (50.0%) were from Israel, 28 (26.4%) were from the United States, and 25 (23.6%) were from Albania. At the time of enrollment, most patients (87.7%) had received prior enzyme replacement therapy (ERT). Thirty-nine of the 106 patients had treatment-emergent adverse events (AEs). Twelve of the 106 patients experienced serious AEs; two patients experienced four treatment-related serious AEs. Four patients died, although none of the deaths was considered to be related to taliglucerase alfa treatment by the treating physicians. Nine patients discontinued from the study, including the four who died. At baseline, patients with prior ERT had a higher mean hemoglobin concentration and platelet counts than treatment-naïve patients, likely reflecting the therapeutic effects of prior treatments. During follow-up, the hemoglobin concentration and platelet counts increased in the treatment-naïve patients and remained relatively constant or increased slightly in patients with prior ERT. Spleen and liver volumes decreased in treatment-naïve patients. Conclusions The interim data showed no new or emergent safety signals. The overall interim data are consistent with the clinical program experience and known safety and effectiveness profile of taliglucerase alfa.

The scientific and therapeutic development of imiglucerase (Cerezyme(®)) by the Genzyme Corporation is a paradigm case for a critical examination of current trends in biotechnology. In this article the authors argue that contemporary interest in treatments for rare diseases by major pharmaceutical companies stems in large part from an exception among rarities: the astonishing commercial success of Cerezyme. The fortunes of the Genzyme Corporation, latterly acquired by global giant Sanofi SA, were founded on the evolution of a blockbuster therapy for a single but, as it turns out, propitious ultra-orphan disorder: Gaucher disease.

Purpose: To evaluate the safety of velaglucerase alfa in patients with type 1 Gaucher disease who received velaglucerase alfa in the US treatment protocol HGT-GCB-058 (ClinicalTrials.gov identifier NCT00954460) during a global supply shortage of imiglucerase. Methods: This multicenter open-label treatment protocol enrolled patients who were either treatment naïve or had been receiving imiglucerase. Patients received intravenous velaglucerase alfa every other week at a dose of 60 U/kg (treatment naïve) or 15–60 U/kg (previously treated). Results: A total of 211 (including six treatment-naïve) patients were enrolled. Among the 205 previously treated patients, 35 (17.1%) experienced an adverse event considered related to study drug. Among the six treatment-naïve patients, one had an adverse event considered related to study drug. Infusion-related adverse events occurred in 28 (13.3%) of the 211 patients and usually occurred during the first three infusions. De novo, nonneutralizing, anti–velaglucerase alfa antibodies developed during treatment in one (<1.0%) previously treated patient and none of the treatment-naïve patients. Conclusion: The currently observed safety profile was consistent with those previously reported for imiglucerase and velaglucerase alfa phase III clinical trials. These results support the safety of initiating treatment with velaglucerase alfa or transitioning patients from imiglucerase therapy to velaglucerase alfa therapy. Genet Med 16 5, 359–366.

Gaucher disease is the most common lysosomal storage disorder, and enzyme replacement therapy, such as administration of imiglucerase, is the standard therapy. Anaphylaxis to imiglucerase is rarely reported. Here, we report a 26-year-old female who was diagnosed with type 1 Gaucher disease and referred to our Allergy Outpatient Clinic because of an anaphylactic reaction due to imiglucerase enzyme therapy. A desensitization protocol was administered with two different dilutions with an increasing rate of administration delivered in 10 consecutive steps by intravenous infusion in an intensive care setting. No reactions occurred during the procedure, and the total final dose of 2,000 U was successfully administered. To our knowledge, this is the first adult case with successful desensitization to imiglucerase. Desensitization protocols to drugs in chronic disease patients for whom no alternative therapies are available can be lifesaving.

Gaucher disease (GD) is the most common lysosomal storage disease, (frequency of 1:40,000 to 1:60,000). Ninety-Five percent of patients have type 1 (nonneuropathic type). Symptomatic patients with type 1 GD are treated with enzyme replacement therapy (ERT) to improve disease-induced effects on hemoglobin, platelets, and liver and spleen volume. Currently, several ERTs are available. The goal of this article was to review the pharmacology, efficacy, and safety data available for the use of a recently approved ERT, velaglucerase alfa, for the treatment of type 1 GD in symptomatic pediatric and adult patients. Serial searches of MEDLINE, EMBASE, and Cochrane databases for English-language, peer-reviewed, clinical data (using the search term velaglucerase alfa) were completed, with the final search in November 2011. All identified, peer-reviewed published human data were used for this review. Due to minimal peer-reviewed published data, those data reported via clinical trial registries or in the form of published abstracts were included. The manufacturer was contacted and given the opportunity to submit supplemental data for consideration of inclusion by the author. Velaglucerase alfa is produced through gene activation technology and is identical to wild-type enzyme. As with other ERTs for type 1 GD, velaglucerase alfa targets accumulated glucocerebroside primarily within the lysosome of the macrophages in the affected organs and systems. When administered at doses of 60 U/kg intravenously, velaglucerase alfa follows linear pharmacokinetics and is rapidly eliminated, with a mean (SD) residence time or time for 63% of the dose to be cleared from systemic circulation of 14 (4) minutes. Four trials and early access program data reporting efficacy were identified for this review: 5 peer-reviewed publications, 3 clinical trial registry reports, and 1 abstract-only publication. Phase I/II data with an extension phase (n = 12) showed significant improvements (all, P < 0.004) in hemoglobin concentrations (21.7%), platelet counts (157.8%), and hepatic (−42.8%) and spleen (−79.3%) volumes at 48 months. Bone mineral density data reported out to 69 months for this extension population noted significant improvements in z score slope for both lumbar spine (0.14 z score unit per year; P < 0.01) and femoral head (0.08 z score unit per year; P < 0.01). Benchmarking of 7 patients with complete clinical datasets at 57 months identified achievement and maintenance of therapeutic goals set by the International Collaborative Gaucher Group for anemia, platelet counts, hepatosplenomegaly, and bone mineral density. Thirty-eight patients enrolled in an open-label, therapy-switch trial who received velaglucerase alfa at doses consistent with current doses of imiglucerase maintained hemoglobin (−0.101 g/dL [95% CI, −0.272 to 0.07]) and platelet counts (7.04% [95% CI, 0.54% to 13.53%]) at 53 weeks after therapy change. Phase III data evaluating 2 dosing regimens of velaglucerase alfa 60 and 45 U/kg intravenously every other week reported significant improvements in most measured clinical parameters at 12 months: hemoglobin concentrations (60 U/kg, 2.429 [0.324] g/dL [P < 0.0001]; 45 U/kg, 2.438 g/dL [95% CI, 1.488 to 3.389]), platelet counts (60 U/kg, 50.88 × 109/L [95% CI, 23.97 to 77.78]; 45 U/kg, 40.92 × 109/L [95% CI, 11.2 to 70.64]), spleen volumes (60 U/kg, −1.92% of body weight [95% CI, −3.04 to −0.79]; 45 U/kg, −1.87% of body weight [95% CI, −3.17 to −0.57]), and hepatic volumes (60 U/kg, −0.84% of body weight [95% CI, −1.58 to −0.11]). A subanalysis of the pediatric population showed clinical improvements at 12 months in both dosing groups: hemoglobin concentrations (60 U/kg, 1.74 g/dL [95% CI, 0.72 to 2.78]; 45 U/kg, 2.77 g/dL [95% CI, −0.99 to 6.53]), platelet counts (60 U/kg, 49.9 × 109/L [95% CI, −32.1 to 131.9]; 45 U/kg, 60.3 × 109/L [95% CI, −103.1 to 223.7]), spleen volumes (60 U/kg, −2.1 cm3 [95% CI, −5.3 to 1.1]; 45 U/kg, −0.7 cm3 [95% CI, −2.6 to 1.2]), and hepatic volumes (60 U/kg, −0.7 cm3 [95% CI, −1.4 to 0.0]; 45 U/kg, −0.3 cm3 [95% CI, −1.7 to 1.1]). Data comparing velaglucerase alfa with imiglucerase identified similar changes in hemoglobin concentrations at 1.624 g/dL and 1.488 g/dL, respectively, after 9 months of therapy. Safety was reported in 3 identified studies and in data reported from the early access program: 3 peer-reviewed publications, 3 studies reported in clinical trial registries, and 1 abstract publication. Patients experienced a minimal number of adverse effects, and most reactions were mild to moderate in severity; 1 patient developed an anaphylactoid reaction and was discontinued from the trial. Antibody formation has been described with velaglucerase alfa but when compared with that of imiglucerase, seroconversion is less frequent (1% and 23%, respectively). Dosing regimens, from 30 to 60 U/kg intravenously every other week, have been assessed. Currently, the manufacturer recommends 60 U/kg intravenously every other week; however, further studies and evaluation of current study dosing regimens are needed to determine if there is a lower effective dose. Although a minimal amount of data are available for this relatively new biological agent, velaglucerase alfa reportedly is effective in the achievement and maintenance of therapeutic goals in type 1 GD in both treatment-naive and patients previously treated with imiglucerase. This agent has been reasonably well tolerated in clinical trials and may be considered for use in symptomatic patients with type 1 GD.