Lusutrombopag: A Review in Thrombocytopenia in Patients with Chronic Liver Disease Prior to a Scheduled Procedure.

Lusutrombopag (Mulpleta®), an orally bioavailable, small molecule thrombopoietin receptor agonist, is approved for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. In placebo-controlled phase 3 clinical trials, lusutrombopag significantly increased the proportion of patients who did not require a platelet transfusion prior to the procedure or rescue therapy for bleeding up to 7 days after the scheduled procedure. Lusutrombopag also significantly increased the proportion of patients who were responders (i.e. had a platelet count ≥ 50 × 109/L and an increase of ≥ 20 × 109/L from baseline) compared with placebo. Lusutrombopag is well tolerated, with headache being the most common adverse reaction in lusutrombopag recipients in clinical trials. Thus, lusutrombopag represents a promising emerging therapeutic option for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure.

Correction to: Migalastat: A Review in Fabry Disease.

The article Migalastat: A Review in Fabry Disease, written by Emma H. McCafferty, Lesley J. Scott, was originally published Online First without open access. After publication in volume 79, issue 5, pages 543-554 [funder] requested that the article be Open Choice to make the article an open access publication. Post-publication open access was funded by [funder]. The article is forthwith distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

Correction to: Vestronidase Alfa: A Review in Mucopolysaccharidosis VII.

The article Vestronidase Alfa: A Review in Mucopolysaccharidosis VII, written by Emma H. McCafferty and Lesley J. Scott, was originally published Online First without open access.

Vestronidase Alfa: A Review in Mucopolysaccharidosis VII.

Mucopolysaccharidosis VII is an extremely rare, autosomal recessive lysosomal storage disorder characterized by a deficiency of ß-glucuronidase activity, resulting in partial degradation and accumulation of GAGs in numerous tissues throughout the body, with consequent cellular damage and organ dysfunction. Enzyme replacement therapy (ERT) with intravenous vestronidase alfa (Mepsevii™), a recombinant form of human ß-glucuronidase, is the first disease-specific therapy approved for the treatment of mucopolysaccharidosis VII in pediatric and adult patients. In the pivotal, blind start, phase 3 trial, 24 weeks of vestronidase alfa therapy significantly reduced urinary GAG (uGAG) excretion in patients with mucopolysaccharidosis VII. Based on a Multi-Domain Responder Index (MDRI; comprises six clinically important morbidity domains, with prespecified minimally important differences for each domain), most evaluable patients experienced an improvement in ≥ 1 domain during the 24-week primary assessment period (overall positive mean change of 0.5 domains). The clinical benefits of vestronidase alfa were sustained during longer-term treatment, as was the reduction in uGAG excretion. Vestronidase alfa has a manageable tolerability profile, with most adverse reactions of mild to moderate severity. Given the lack of treatment options and the clinical benefits it provides, intravenous vestronidase alfa is an important emerging ERT for patients with mucopolysaccharidosis VII.

Migalastat: A Review in Fabry Disease.

Fabry disease is a rare lysosomal disorder characterized by deficient or absent α-galactosidase A activity resulting from mutations in the GLA gene. Migalastat (Galafold™), a pharmacological chaperone, stabilizes and facilitates trafficking of amenable mutant forms of α-galactosidase A enzyme from the endoplasmic reticulum to lysosomes and increases its lysosomal activity. Oral migalastat is the first pharmacological chaperone approved for treating patients [aged ≥ 18 years (USA and Canada) or ≥ 16 years in other countries] with Fabry disease who have a migalastat-amenable GLA mutation. In the FACETS trial in enzyme replacement therapy (ERT)-naive patients with GLA mutations amenable or non-amenable to migalastat, there was no significant difference between the migalastat and placebo groups for the proportion of patients achieving a ≥ 50% reduction in the number of globotriaosylceramide (GL-3) inclusions/kidney interstitial capillary (KIC) at 6 months [primary endpoint; intent-to-treat (ITT) population]. In the modified ITT population (i.e. patients with migalastat-amenable GLA mutations), relative to placebo, migalastat treatment significantly reduced the mean number of GL-3 inclusions/KIC and plasma lyso-globotriaosylsphingosine levels at 6 months. Among evaluable patients, migalastat maintained renal function and reduced cardiac mass after ≤ 24 months' therapy. In the ATTRACT trial in ERT-experienced patients, renal function was maintained during 18 months of migalastat or ERT; however, migalastat significantly reduced cardiac mass compared with ERT. Migalastat was generally well tolerated in both of these trials. Given its convenient oral regimen and the limited therapeutic options available, migalastat is an important treatment option for Fabry disease in patients with migalastat-amenable GLA mutations.

Dasatinib: A Review in Pediatric Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is a rare hematopoietic stem cell disease that is typically characterized by the abnormal BCR-ABL1 fusion gene on the Philadelphia (Ph) chromosome in neoplastic cells. Dasatinib (Sprycel®) is an orally administered, small molecule tyrosine kinase inhibitor indicated for the treatment of certain hematological malignancies, including Ph-positive CML in the chronic phase (Ph+ CML-CP) in adult and pediatric patients. In open-label phase 1 and phase 2 clinical trials, dasatinib produced early and durable target responses (i.e. molecular, cytogenetic and/or hematologic) in pediatric patients with Ph+ CML-CP that was newly diagnosed or resistant/intolerant to imatinib, with some recipients of the drug also experiencing deep molecular responses. Dasatinib therapy in pediatric patients with Ph+ CML-CP was reported to have a similar safety profile to that observed in adults, except there were no occurrences of pleural effusion, pericardial effusion, pulmonary edema, or pulmonary hypertension adverse events. Although long-term outcomes remain to be determined, dasatinib expands the first- and second-line options available for the treatment of Ph+ CML-CP in pediatric patients.