BOSTON — Maralixibat demonstrated durable control of serum bactericidal antibody, pruritus, and xanthoma in children with Alagille syndrome, according to data from the ICONIC study presented at The Liver Meeting 2019.
“Alagille syndrome is a rare genetic, multisystem, development disease,” Emmanuel M. Gonzales, MD, from the University Hospitals of Paris-Sud Bicêtre in France, said during his presentation. “Alagille syndrome may involve many different organs and is associated with growth deficit. Currently, there are no approved pharmacological treatments for this syndrome and liver transplantation may be used to improve quality of life in these children.”
Maralixibat (Mirum Pharmaceuticals) is an oral, minimally absorbed, selective inhibitor of apical sodium-dependent bile acid transporter (ASBT). Clinical effects of ASBT inhibition have demonstrated decreases in pruritus, serum bactericidal antibody (sBA) levels, and cholesterol, while increasing C4 in primary biliary cholangitis.
Gonzales presented data from a long-term open extension of the core ICONIC study. Twenty-nine patients who reached week 48 of the ICONIC study and were eligible to continue treatment with maralixibat 400 µg/kg, increasing from once daily to twice daily.
Fifteen patients remained on maralixibat with a median duration of 44.5 months (range, 42.1-51.7 months).
Patients had significant reductions in serum bactericidal antibody (sBA) levels (259 vs. 97.3 µmol/L; P = .0047), Itch Reported Outcome (ItchRO) score (2.8 vs. 0.33; P < .0001), serum cholesterol (414.3 vs. 277.5 mg/dL; P < .01), C4 levels (7.4 vs. 30.4 ng/mL; P = .04), xanthoma score (0.9 vs. 0.1; P = .0285), and height z scores (–1.82 vs. –1.37; P < .01) compared with baseline.
Maralixibat was generally safe and well tolerated during long-term treatment with no increases in frequency or severity of adverse events from the core study. Gonzales and colleagues observed asymptomatic and reversible ALT and aspartate aminotransferase elevations that were isolated and similar to those reported in natural history studies.
Additionally, treatment with 400 µg/kg twice daily had a similar efficacy and safety profile compared with once-daily dosing.
“Long-term treatment with maralixibat in patients with Alagille syndrome was associated with significant and durable improvements in pruritus, serum bile acids, quality of life, cholesterol, xanthoma, and height growth,” Gonzales concluded. – Talitha Bennett
Reference: Gonzales EM, et al. Abstract LO3. Presented at: The Liver Meeting; Nov. 7-12, 2019; Boston.
Disclosure: Gonzales reports he is a consultant for Albireo, Laboratories CTRS and Mirum Pharmaceuticals.