Drugs
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Spinal muscular atrophy (SMA) is a rare autosomal recessive disorder characterized by muscle atrophy and weakness resulting from motor neuron degeneration in the spinal cord and brainstem. It is most commonly caused by insufficient levels of survival motor neuron (SMN) protein (which is critical for motor neuron maintenance) secondary to deletions or mutations in the SMN1 gene. Nusinersen (SPINRAZA™) is a modified antisense oligonucleotide that binds to a specific sequence in the intron, downstream of exon 7 on the pre-messenger ribonucleic acid (pre-mRNA) of the SMN2 gene. ⋯ Nusinersen is approved in the USA for intrathecal use in paediatric and adult patients with SMA. Regulatory assessments for nusinersen as a treatment for SMA are underway in the EU and several other countries. This article summarizes the milestones in the development of nusinersen leading to this first approval for SMA in paediatric and adult patients.
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Adoptive immunotherapy with chimeric antigen receptor-modified (CAR)-T cells is a rapidly growing therapeutic approach to treating patients with refractory cancer, with over 100 clinical trials in various malignancies in progress. The enthusiasm for CAR-T cells has been driven by the clinical success of CD19-targeted CAR-T cell therapy in B-cell acute lymphoblastic leukemia, and the promising data in B-cell non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Despite the success of targeting CD19 with CAR-T cells in early clinical studies, many challenges remain to improve outcomes, reduce toxicity, and determine the appropriate settings for CAR-T cell immunotherapy. Reviewing the lessons learned thus far in CD19 CAR-T cell trials and how some of these challenges may be overcome will help guide the development of CAR-T cell therapy for malignancies of B-cell origin, as well as for other hematopoietic and non-hematopoietic cancers.
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Subcutaneous teduglutide (Revestive®), a glucagon-like peptide-2 analogue that increases intestinal absorption, is approved in the EU for the treatment of short bowel syndrome (SBS) in patients aged ≥1 year who are stable following a period of postsurgical intestinal adaptation. In a phase III trial in adults with SBS intestinal failure (IF) dependent on parenteral support (PS), a significantly greater proportion of teduglutide 0.05 mg/kg/day than placebo recipients achieved a ≥20% reduction in weekly PS volume from baseline to week 20 and maintained it to week 24. The proportion of patients who had a reduction in one or more days on PS was also significant with teduglutide compared with placebo. ⋯ Results from a phase III trial in paediatric patients with SBS-IF dependent on PS were consistent with those in adults. Adverse events were mostly of mild to moderate severity and generally consistent with the underlying condition or known mechanism of the drug (e.g. central line-related issues, gastrointestinal events). Teduglutide is therefore a useful treatment option in children (aged ≥1 year), adolescents and adults with SBS.