A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults: One-year results

Wasserstein, Melissa P.; Lachmann, Robin; Hollak, Carla E. M.; Arash-Kaps, Laila; Barbato, Antonio; Gallagher, Renata C.; Giugliani, Roberto; Guelbert, Norberto; Ikezoe, Takayuki; Lidove, Olivier; Mabe, Paulina; Mengel, Eugen; Scarpa, Maurizio; Senates, Eubekir; Tchan, Michel; Villarrubia, Jesús; Chen, Yixin; Furey, Sandy A.; Thurberg, Beth L.; Zaher, Atef; Kumar, Monica

doi:10.1016/j.gim.2022.03.021

Cited by 34 publications

(79 citation statements)

References 32 publications

(68 reference statements)

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“…Olipudase alfa (Xenpozyme ® ) is a recombinant human ASM enzyme replacement therapy (ERT) approved for the treatment of the non-central nervous system manifestations of ASMD in children and adults. Olipudase alfa is well-tolerated in adults [11][12][13] and pediatric [14] patients with chronic ASMD after a within-patient dose escalation regimen designed to gradually debulk tissue sphingomyelin [15,16]. Olipudase alfa was associated with clinically significant improvements in disease pathology and multiple endpoints compared with placebo in adults with ASMD [13].…”

mentioning

confidence: 99%

“…Olipudase alfa is well-tolerated in adults [11][12][13] and pediatric [14] patients with chronic ASMD after a within-patient dose escalation regimen designed to gradually debulk tissue sphingomyelin [15,16]. Olipudase alfa was associated with clinically significant improvements in disease pathology and multiple endpoints compared with placebo in adults with ASMD [13]. In pediatric patients with chronic ASMD, an open label single-arm study demonstrated improvements across a range of endpoints after 1 year of treatment [14].…”

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confidence: 99%

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Long-term safety and clinical outcomes of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency: two-year results

Diaz

Giugliani

Guffon

et al. 2022

Orphanet J Rare Dis

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Background Olipudase alfa is a recombinant human acid sphingomyelinase (ASM) enzyme replacement therapy (ERT) for non-central-nervous-system manifestations of acid sphingomyelinase deficiency (ASMD). We report 2-year cumulative safety and efficacy data after olipudase alfa treatment in 20 children (four adolescents [12–17 year], nine children [6–11 year], and seven infants/early child [1–5 year]) with baseline splenomegaly and growth deficits who completed the 1-year ASCEND-Peds clinical trial (NCT02292654) and who continue to receive olipudase alfa in a long-term study (NCT02004704). Efficacy endpoints include spleen and liver volumes, diffusing capacity of the lung for carbon monoxide (DLCO), high-resolution computed tomography (HRCT) lung imaging, lipid profiles, liver function tests, and height Z-scores. Results All 20 former ASCEND-Peds patients completed at least 2 years of olipudase alfa treatment. No patient discontinued and no new safety issue arose during the second year of treatment; 99% of adverse events were mild or moderate. During year 2, one patient had two treatment-related serious events of hypersensitivity that resolved. Mean reductions from baseline in spleen and liver volumes were 61% and 49%, respectively (p < 0.0001) and mean percent-predicted-DLCO increased by 46.6% (p < 0.0001) in nine patients who performed the test at baseline. Lipid profiles and elevated liver transaminase levels that improved or normalized by 1 year remained stable. Mean height Z-scores improved in all age groups (mean change from baseline 1.17, P < 0.0001). Conclusion Olipudase alfa was generally well-tolerated during 2 years of treatment. Improvements in clinically relevant disease endpoints observed during the first year of treatment were maintained or augmented in the second year. Trial registration NCT02004704 registered 26 Nov 2013, https://clinicaltrials.gov/ct2/show/record/NCT02004704.

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confidence: 99%

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confidence: 99%

Long-term safety and clinical outcomes of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency: two-year results

Diaz

Giugliani

Guffon

et al. 2022

Orphanet J Rare Dis

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“…The novel mutation site (c.829 T > C in exon 2 of the SMPD1 gene) in this case has not been reported in the literature thus far and needs to be further confirmed. Of note, specific enzyme replacement therapy for NPDB may soon become available since clinical trials using olipudase alfa in adult and paediatric patients have shown significant improvements across several clinically relevant endpoints, particularly spleen size and DLCO [12][13][14]. This treatment, however, is currently not approved by regulatory agencies, except in Japan.…”

Section: Discussionmentioning

confidence: 99%

Three-years misdiagnosis of Niemann Pick disease type B with novel mutations in SMPD1 gene as Budd-Chiari syndrome

Zhou

Wang

et al. 2022

BMC Med Genomics

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Background The chronic visceral subtype of acid sphingomyelinase deficiency, commonly known as Niemann Pick disease type B (NPDB), is a relatively rare autosomal recessive genetic disorder that is caused by mutations in the SMPD1 gene. NPDB with sea-blue histiocytes (SBH) clinically mimics Budd-Chiari syndrome (BCS), as it lacks specific clinical characteristics. This makes its diagnosis difficult. Case presentation Here, we report a case of NPDB with SBH that was misdiagnosed as BCS for three years. A 20-year-old female with abdominal distension, hepatosplenomegaly, and haematological anomalies was initially diagnosed with BCS based on her imaging finding of a thin hepatic vein and rapid blood flow at the confluence of the hepatic vein and inferior vena cava. Her bone marrow cytology found sea-blue histiocytes. Liver biopsy showed foamy cytoplasm in hepatocytes surrounded by numerous Kupffer cells. Sequencing analysis of the SMPD1 gene led to the finding of two missense mutations in the heterozygous state: C.829 T > C (p.Trp277Arg) in exon 2 (novel) and c.1805G > A (p.Arg602His) in exon 6 (already described). These findings established the diagnosis of NPDB. Conclusion The patient presented with hepatosplenomegaly, haematological anomalies, and dyslipidaemia. Thus, NPDB should be considered following the exclusion of related diseases. The diagnosis of NPDB was suspected by clinical symptoms and routine laboratory tests and was confirmed by liver biopsy and gene sequencing. The novel mutation c.829 T > C in exon 2 of the SMPD1 gene has never been reported and needs to be further investigated.

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“…Xenopus is the first disease-specific peptide approved by the FDA for treating the non-central nervous system (CNS) manifestations of acid sphingomyelinase deficiencies in adult and pediatric patients (19). Over time, deficiency in acid sphingomyelinase leads to decreased lung function, enlarged liver and/or spleen, and growth delay in children (20). Xenopus delivers olipudase alfa-rpcp, an enzyme replacement therapy, to cells to reduce sphingomyelin production by providing acid sphingomyelinase that allows sphingolipids to be destroyed (21).…”

Section: Xenpozyme™ (Olipudase Alfa-rpcp)mentioning

confidence: 99%

“…Xenopus delivers olipudase alfa-rpcp, an enzyme replacement therapy, to cells to reduce sphingomyelin production by providing acid sphingomyelinase that allows sphingolipids to be destroyed (21). Olipudase alfa-rpcp is a hydrolytic lysosomal sphingomyelin-specific enzyme composed of 570 amino acids with a molecular weight of 76 kDa, produced in a Chinese hamster ovary cell line using recombinant DNA technology (20). XENPOZYME (olipudase alfa-rpcp) was approved in Japan on 28 March 2022 for the first time.…”

Section: Xenpozyme™ (Olipudase Alfa-rpcp)mentioning

confidence: 99%

Current Status of Peptide Medications and the Position of Active Therapeutic Peptides with Scorpion Venom Origin

Baradaran

2023

Jundishapur J Nat Pharm Prod

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: Peptides are highly potent, selective, and relatively safe therapeutics. Over the past two decades, natural peptides have been obtained, studied, and eventually approved by the Food and Drug Administration (FDA) due to advancements in identification, production, modification, and analytical technologies. Some peptide therapeutics has been derived from the venom gland of venomous animals, including snake, leech, lizard, snail, and scorpion. Scorpion was identified as a reservoir of important peptides with pharmaceutical properties. The scorpion uses these peptides for capturing prey and defense. However, their pharmacological properties in treating different diseases, including cardiac problems, autoimmune and infectious diseases, and diverse cancers, have been confirmed. Ion channel modifiers are the greatest components of the scorpion venom glands. Due to advances in proteomic and transcriptomic approaches, the identification of new scorpion venom peptides is steadily increasing. In this review, we tried to represent the current status of peptide medicines and describe the last peptide medications approved by FDA in 2022. Moreover, we will further explain potent peptides originating from scorpion venom, which have gone through important steps to be approved.

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A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults: One-year results

Cited by 34 publications

References 32 publications

Long-term safety and clinical outcomes of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency: two-year results

Long-term safety and clinical outcomes of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency: two-year results

Three-years misdiagnosis of Niemann Pick disease type B with novel mutations in SMPD1 gene as Budd-Chiari syndrome

Current Status of Peptide Medications and the Position of Active Therapeutic Peptides with Scorpion Venom Origin

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