Autor:innen:
S. Jones (Manchester, GB)
S. Vijay (Birmingham, GB)
S. Fecarotta (Naples, IT)
A. Gosh (Manchester, GB)
K. Allen (New Haven, CT, US)
M. Friedman (New Haven, CT, US)
F. Abel (New Haven, CT, US)
Two studies (VITAL/CL08) are evaluating the safety and efficacy of enzyme replacement with sebelipase alfa (SA) in infants with rapidly progressive lysosomal acid lipase deficiency (LAL-D). Nineteen infants were enrolled (VITAL, n=9; CL08, n=10). Median age at treatment initiation for VITAL/CL08 was 3.0/2.8 months. As of August 2017, 13 patients continue on study or completed the study; 6 have died. Five are ≥3 years old (all in VITAL) and have been receiving SA for 228-263 weeks. All patients experienced ≥1 serious adverse event (SAE). Seven (37%) had treatment-related SAEs; of these, 5 had infusion-associated reactions (IARs), including 1 patient with an IAR who also had pyrexia. Among patients who did not have an IAR, 1 developed anti-drug antibodies (ADAs), and 1 had pyrexia, pallor, chills, and tachycardia. All SAEs resolved. None discontinued treatment because of tolerability/IARs. Of 17 patients tested for ADAs, 10 had detectable titers; of these, 8 developed neutralizing antibodies, with no apparent effects on safety/efficacy. Median serum alanine aminotransferase levels, 145.0 U/L at baseline (BL, n=9) in VITAL, decreased by 29.6% at week 48 (n=4), 7.4% at week 96 (n=5), and 12.5% at week 144 (n=5); 37 U/L at BL (n=9) in CL08, they showed no change at week 48 (n=7), decreased by 55.2% at week 96 (n=5), and decreased by 90.3% at week 144 (n=2). Serum hemoglobin and albumin levels also improved. Median weight centile, 3.1 (n=8) at BL, increased by 7.5 (n=4) at week 48, 21.8 (n=5) at week 96, and 14.0 (n=5) at week 144 in VITAL; and 0.2 (n=9) at BL in CL08, increased by 27.2 (n=7) at week 48, 45.5 (n=5) at week 96, and 61.7 (n=3) at week 144.
In conclusion, SA is associated with prolonged survival, favorable tolerability, and sustained improvements in disease activity parameters in infants with LAL-D.