FDA Approvals Roundup: Livmarli and Tecartus
A weekly update on new drug approvals and indications from the US Food and Drug Administration (FDA).New approval
Livmarli approved for cholestatic pruritus in children with Alagille syndrome
Mirum’s Livmarli (maralixibat oral solution) has been approved for treating cholestatic pruritus in patients aged 1 year or older who have Alagille syndrome (ALGS).
ALGS is a rare genetic disorder caused by abnormalities in bile ducts that can lead to progressive liver disease. Cholestatic pruritus is a sensation of itch associated with liver disease.
The approval of Livmarli, an ileal bile acid transporter inhibitor, was based on findings from the pivotal ICONIC study and supported by 5 years of data from supportive studies in a total of 86 patients.
In the long-term, open-label ICONIC study, which had a double-blind, placebo-controlled, randomized drug withdrawal period, 31 patients from the indicated population received Livmarli once daily for 18 weeks, after which 29 were randomized to receive Livmarli or placebo for 4 weeks. All 29 patients then received open-label Livmarli for an additional 26 weeks. Pruritis severity was rated on a scale of 0 (no itch) to 4 (very severe) twice daily by a caregiver given the young age of most participants (median, 5 years; range, 1-15 years).
Pruritis score was 3.1 at baseline and 1.4 at the end of 18 weeks of open-label treatment. At week 22, the pruritis score was 1.6 for Livmarli patients and 3.0 for placebo, reflecting changes of 0.2 and 1.6, respectively, from the 18-week score. Six weeks after re-entering the open-label retreatment phase, patients from both treatment groups had similar pruritis scores. Caregiver scores were found to be similar to patient-rated scores by patients old enough to self-report.
New indication
Tecartus approved for relapsed/refractory ALL
Kite’s Tecartus (brexucabtagene autoleucel) has been granted a new indication for treating adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
The expanded approval was based on efficacy findings from the phase 1/2 single-arm, multicenter ZUMA-3 trial in which patients from the indicated population received a single infusion of Tecartus after lymphodepletion. Of the 54 evaluable patients, 28 (52%) achieved complete response (CR) within 3 months (median time, 56 days). Median duration of CR was not reached during the median follow-up of 7.1 months but was estimated to exceed 12 months for more than half the patients.
The review used the assessment aid. The application was granted priority review and breakthrough and orphan drug designations.
Tecartus, a CD 19-directed chimeric antigen receptor T-cell therapy, received accelerated approval in 2020 for treating adults with relapsed or refractory mantle cell lymphoma. The prescribing information has a boxed warning for cytokine release syndrome and neurologic toxicities.
