Sustained reduction in pruritus seen with MRX in children with Alagille syndrome
Children with Alagille syndrome who received 48 weeks of Maralixibat had clinically meaningful reduction in pruritus and improvements in quality of life, according to a presentation at The Liver Meeting Digital Experience.
Benjamin L. Shneider, MD, from the department of pediatrics and the division of pediatric gastroenterology, hepatology and nutrition at Baylor College of Medicine and Texas Children’s Hospital, said the changes persisted for 96 weeks in patients who continued to receive Maralixibat (MRX; Mirum Pharmaceuticals).
“Initial data from the multi-institutional IMAGINE II clinical trial, demonstrated that prolonged treatment with maralixibat resulted in clinically meaningful improvements in debilitating itching (pruritus) and related quality of life outcomes for children with Alagille syndrome,” Benjamin Shneider, MD, chief of pediatric gastroenterology, hepatology and nutrition at Texas Children’s Hospital, and George Peterkin endowed chair and professor of pediatrics at Baylor College of Medicine, told Healio Gastroenterology. “At the end of over 96-weeks of treatment, 90% and 80% of the participants who were able to receive maralixibat to that time point had clinically meaningful responses. We were particularly excited to see that 25% of participants showed dramatic four-point reduction in itching on the clinician scratch scale.”
Shneider and colleagues selected 34 patients from the 37 patients with Alagille syndrome who were enrolled in the ITCH multi-center, placebo-controlled trial for the new IMAGINE II trial. Blinded dose escalation of maralixibat occurred during the first 4 weeks of the IMAGINE II trial among patients who were on placebo during the ITCH trial. During weeks 5 through 12, investigators optimized the dose up to 280 g/kg per day.
“As tolerated, MRX dosing was then unchanged for up to 216 weeks with monitoring of pruritus using patient reported outcomes [ItchRO(observer), 0 to 4 (increasing pruritus severity)], [pediatric quality of life (PedsQL)] and clinician scratch score (CSS, 0 to 4),” Shneider and colleagues wrote. “Clinically meaningful response (CR) from baseline of ItchRO and CSS was defined as –1, while PedsQL was +5.”
Every 12 weeks, investigators conducted safety and efficacy evaluations.
Results showed mean ItchRO and CSS decreased from ITCH baseline to week 48 of IMAGINEII; whereas PedsQL increased (percentage of patients with CR: ItchRO –1.9; 80.8%, CSS –1.9; 77.8%, PedsQL +10.2; 53.8%). Investigators reported a stability of response through week 96 (ItchRO –2.2; 86.4%, CSS –2.1; 83.3%, PedsQL +9.7; 61.1%) and after for an average of 92 additional weeks in selected patients (ItchRO –2.3; 90.5%, CSS –2; 80.0%, PedsQL +6.5; 44.4%). Cholesterol, serum bile acids and platelets decreased and ALT and GGT increased at week 48; whereas total bilirubin and albumin did not change.
According to researchers, with 96 weeks of maralixibat, the height and weight z scores increased. During IMAGINE II, seven patients had a least one serious adverse event. Fourteen patients withdrew prior to the completion of IMAGINE II.
“Although further complex analyses of this data and others is still needed to determine the impact of maralixibat on other aspects of the liver disease in Alagille syndrome, finding a drug that effectively treats pruritus is truly a game-changer for children and families who struggle with Alagille syndrome,” Shneider said.