# Twice weekly dosing with Sebelipase alfa (Kanuma®) rescues severely ill infants with Wolman disease

## TL;DR

A higher dosing schedule of Sebelipase alfa improves survival in infants with severe Wolman disease by boosting lipid clearance.

## Contribution

Demonstrates the efficacy and safety of a twice-weekly dosing regimen of Sebelipase alfa in severely ill infants.

## Key findings

- Twice-weekly dosing increases LAL activity and reduces oxysterol levels effectively.
- The regimen is well tolerated and leads to improved clinical outcomes in infants.
- Lipid accumulation still occurs between doses, indicating potential for further optimization.

## Abstract

Sebelipase alfa (Kanuma®) is approved for patients with Wolman disease (WD) at a dosage of 3–5 mg/kg once weekly. Survival rates in the second of two clinical trials was greater, despite recruiting more severely ill patients, probably related to higher initial and maximal doses. We aimed to evaluate the effective pharmacokinetics and pharmacodynamics of Sebelipase alfa when administered to patients with severe WD at 5 mg/kg twice weekly, an intensive regimen which was not assessed in the trials.

We recruited 3 patients receiving Sebelipase alfa 5 mg/kg twice weekly. We measured LAL activity in leukocytes and plasma oxysterol concentration in two patients and LAL activity in fibroblasts in one patient. Clinical follow up was also assessed.

Analyses of LAL activity and oxysterols demonstrate that there is short-lived enzyme activity post-dosing which is associated with the release of stored lipids. Clinical data demonstrate that 5 mg/kg twice weekly dosing is well tolerated and effective.

5 mg/kg twice weekly dosing with Sebelipase alfa rescues severely ill infants with WD by increasing substrate clearance. There is biologically relevant lipid accumulation in the ‘trough’ periods before the next dosing, even with this intensive regimen.