Agalsidase alfa

A 10-year-old boy diagnosed with Fabry disease was also found to have a rare blood disorder called congenital dyserythropoietic anemia (CDA) in a case researchers said was highly unusual.In CDA, anemia, that is, a shortage of red blood cells that transport oxygen in the bloodstream, results in symptoms like fatigue, weakness, and pale skin.“CDA … and [Fabry disease] co-occurring in the same patient is a very rare medical finding [that] has never been reported,” the researchers wrote. “This case … underscores the need for further investigation into potential genetic and [disease-causing] links between these seemingly disparate conditions.”The case was described in “The unlikely combination: Anderson–Fabry disease and congenital dyserythropoietic anemia type II in a pediatric patient,” in Clinical Case Reports.The boy was started on treatment with agalsidase alfa, an enzyme replacement therapy for Fabry, but no follow-up data regarding his treatment outcomes was provided.Fabry disease is caused by mutations in the GLA gene, which provides instructions for producing the alpha-galactosidase A (alpha-Gal A) enzyme. The mutations typically affect the activity of alpha-Gal A and lead to fat molecules — mainly globotriaosylceramide (Gb3) and lyso-Gb3 —  accumulating in several tissues and organs. Symptoms include pain, gastrointestinal issues, and skin rash, and may involve the kidneys, heart, and nervous system.The boy was admitted to a pediatric clinic having had a pale appearance and recurrent infections in the previous months. A physical exam showed his vital signs were stable and he had normal growth, but an ultrasound revealed an enlarged spleen.Laboratory work indicated low hemoglobin, the protein that carries oxygen in red blood cells, and high levels of total bilirubin, although direct bilirubin was in the normal range. Total bilirubin includes indirect bilirubin, the one that results from the breakdown of red blood cells, and direct bilirubin, an indicator of liver function.The boy had ferritin levels that were just above the lower normal range. Ferritin is a protein that stores iron needed to make healthy red blood cells. The boy was treated with folic acid and iron supplements, which didn’t significantly increase his hemoglobin or reduce the levels of total bilirubin.Whole genome sequencing, which allows for the sequencing of a person’s complete genetic information, revealed genetic mutations consistent with Fabry disease, which, together with lower than normal alpha-GalA activity confirmed the disease diagnosis.The boy also had a mutation that led to a CDA type 2 diagnosis. This CDA type is the most common one and is marked by anemia, and liver and spleen enlargement. He was referred to a pediatric neurologist and started treatment with agalsidase alfa every two weeks. Agalsidase alfa is an enzyme replacement therapy, meaning it provides a working version of the alpha-Gal A enzyme to ease Fabry symptoms. The treatment is approved as Replagal in Europe and other countries, but not in the U.S.No information about the result of treatment was provided by the researchers.“The combined form of both entities of disorders isn’t widely known. Since both CDA and [Fabry disease] are rare genetic disorders, the likelihood of an individual having both conditions simultaneously is exceedingly low,” the researchers wrote. “To the best of our knowledge, it is the first case of [Fabry disease] and CDA type II, coexisting in a 10-year-old boy.”

Chiesi has announced that the Scottish Medicines Consortium (SMC) has approved its two rare disease therapies, Elfabrio (pegunigalsidase alfa) and Filsuvez (birch bark extract gel), to treat Fabry disease and junctional and dystrophic epidermolysis bullosa (EB), respectively. Elfabrio has been indicated for use in adults living with the debilitating genetic disease, while Filsuvez has been approved for use in patients aged six months and older, subject to data collection under the SMC’s ultra-orphan medicines framework expected by September. Rare diseases affect around 436,000 people in Scotland and the SMC’s approval aligns with the Scottish government’s action plan for rare diseases by improving access to specialist treatments, one of the four key priorities outlined in the UK Rare Diseases Framework. The SMC’s decision on Elfabrio, a novel enzyme replacement therapy, was based on positive results from phase 3 clinical trials involving 142 Fabry disease patients, of whom 112 received Elfabrio 1mg every other week, and comes after the National Institute for Health and Care Excellence recommended the therapy in 2023. The studies showed that Elfabrio was well tolerated and was similarly clinically effective and more cost-effective compared to the current treatments being used in the NHS, agalsidase alfa and migalastat. Affecting around one in 40,000 people, Fabry disease is a rare, progressive, X-linked inherited lysosomal storage disorder that causes chronic pain and progressive damage to vital organs, including the heart, kidneys and brain. Previously approved by the European Medicines Agency, Filsuvez is a sterile gel for cutaneous application used for the treatment of partial-thickness wounds associated with dystrophic and junctional EB and is currently the only licenced therapy for this patient population. EB is a heterogenous group of rare inherited skin disorders caused by mutations in the genes that encode skin anchoring proteins of the dermo-epidermal junction and is characterised by fragile skin that is prone to blistering and erosions due to minor trauma or friction anywhere on the body. Commenting on the approvals, David Garzón Lafuente, head of rare diseases, Chiesi UK and Ireland, said: “The positive announcements for [Elfabrio] and [Filsuvez] by the SMC are a result of close collaborative working between patient organisations… to support as many people living with a rare disease as possible.”