November 07, 2017
2 min read

Novel therapy increases survival in infants with Wolman disease

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Eight out of 10 infants treated with Kanuma for lysosomal acid lipase deficiency survived beyond age 1 year, according to a press release from Alexion Pharmaceuticals. Patients also had improved weight gain and lipid biomarker levels.

“This was a universally fatal disease for which we now have a treatment,” Simon Jones, MD, from the University of Manchester, United Kingdom, told “This lysosomal storage disorder is like all of the other [lysosomal storage diseases] in that there’s a spectrum.”

Simon Jones, MD
Simon Jones

“Kids who have no functional enzyme at all present very early in life, even sometimes before birth there is enlarged liver, and have a very rapidly progressive disease with a very early death,” he said. “Children who have slightly less severe disease, with a little bit of residual enzyme activity, usually present much later on, usually in childhood or young adulthood with a much more slowly progressive disease.”

Jones and colleagues presented data from their ongoing study at the recent NASPGHAN Annual Meeting in Las Vegas. The study included 10 patients aged younger than 8 months with lysosomal acid lipase deficiency (LAL-D), also known as Wolman disease. Patients received 1 mg/kg of Kanuma (sebelipase alfa, Alexion) once per week. The dose increased to at least 3 mg/kg for those who survived to age 12 months.

As of August 2017, eight patients have survived, with a median age of 29.8 months (range, 16.5-39.4 months). One of the 10 patients died at age 5 months and one died at age 13.8 months. The researchers do not consider either death related to treatment.

Investigators estimated a 90% chance of survival to 12 months in infants treated with sebelipase alfa for LAL-D.

“What is critical at this point is to recognize and diagnose these patients early,” Jones said. “They can report to a range of different pediatric specialties. They can present to the general pediatrician, they can present to the gastroenterologist with diarrhea, vomiting ... and to the hepatologist with liver disfunction, and they can even present to the hematologist/oncologist because they often have a very inflammatory appearance.”

Based on percentiles from the WHO growth chart, median weight-for-age percentile increased from 0.15 at baseline to 37.8 at week 48 of treatment for an overall median increase of 27.2 from baseline.

Additionally, LDL decreased in two patients from 118.8 mg/dL at baseline by a median 47.5% at 48 weeks and HDL increased in three other patients from 9.4 mg/dL at baseline by 33.3% at 49 weeks.


While alanine aminotransferase levels did not change by week 48, median aspartate aminotransferase levels decreased from 99.5 U/L by 35.3% in six patients. At week 48, albumin levels increased by 30% from 20 g/L at baseline in seven patients; hemoglobin increased by 27.1% from 90 g/L in five patients; and platelet count increased by 54.3% from 146 µL in five patients.

Treatment emergent adverse events occurred in all patients and six patients experienced serious adverse events related to treatment that later resolved.

“This disease needs to be diagnosed within days or weeks if we are to have an opportunity to treat them. Early diagnosis is key; yes, it’s a rare disease, but early diagnosis gives us a chance to treat them,” Jones concluded. “This was a hugely important group to try and treat because really there has been nothing formal up until this point. We had tried occasionally bone marrow transplants in this group before, but the vast majority did not survive that. I’ve spent a lot of time developing enzyme replacement therapy for lysosomal disorders and this has been the most dramatically affective treatment for a long time.” – by Talitha Bennett

Disclosure: Jones reports he was an investigator for Kanuma and has served as a consultant to Alexion.