Orphan drugs used to treat diseases caused by inborn errors of metabolism like lysosomal acid lipase deficiency (LAL-D) show many disparities in effectiveness and a high economic impact, according to a new study published in Anales de Pediatría. However, they have an easy toxicity profile to manage.

“The cost-effectiveness ratio for orphan drugs is a controversial issue due to their high cost and the inconclusive clinical evidence,” the authors said.

To describe the effectiveness of orphan drugs in treating children with inborn errors of metabolism, a team of researchers from Hospital San Pedro in Logroño, Spain conducted a retrospective descriptive study in patients diagnosed with such diseases during childhood and who attended their hospital.

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A total of 15 children, median age 17.8 years were diagnosed with 7 different inborn errors of metabolism, of which 1 was LAL-D. The patient with LAL-D was a 14-year-old boy who had faltering growth since he was aged 2 years.

He was asymptomatic and disease manifestations were limited to sinus bradycardia and hepatosplenomegaly with microvesicular steatosis. He was treated with the enzyme replacement therapy sebelipase alfa every 2 weeks at a dose of 35 mg. This led to an improvement in his lipid profile and liver enzymes.

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The children who attended Hospital San Pedro were treated with 9 different drugs. These were sodium phenylbutyrate, succinate, miglustat, velaglucerase, 5-hydroxytryptophan, sebelipase, sapropterin, idursulfase, and riboflavin. 

Most patients tolerated the drugs well with only 1 patient with Hunter syndrome developing paroxysmal supraventricular tachycardia following idursulfase treatment. Although some drugs cleared the symptoms of the disease, others only led to modest improvements.

The cost of orphan drugs accounted for 1.3% of hospital drug costs. Multicentre studies with larger sample sizes are necessary to assess the effectiveness of orphan drugs in the treatment of inborn errors of metabolism, the authors concluded.


Caso-González A, Núñez-Rodríguez J, Nebot-Villacampa MJ, et al. Clinical experience with orphan drugs for rare metabolic diseases. An Pediatr. 2022;96(1):8-16. doi:10.1016/j.anpede.2020.09.014