Livmarli Approved for Cholestatic Pruritus in Progressive Familial Intrahepatic Cholestasis

The Food and Drug Administration (FDA) has approved Livmarli^® (maralixibat) for the treatment of cholestatic pruritus in patients 5 years of age and older with progressive familial intrahepatic cholestasis (PFIC).

The approval was based on data from the 26-week randomized, placebo-controlled phase 3 MARCH-PFIC trial (ClinicalTrials.gov Identifier: NCT03905330), which evaluated the efficacy and safety of maralixibat, an ileal bile acid transporter (IBAT) inhibitor, in patients 5 years of age and older with PFIC with presence of biallelic known pathogenic variants (eg, PFIC1, PFIC2, PFIC3, PFIC4, or PFIC6). 

At baseline, most patients were on stable ursodeoxycholic acid (89.1%) or rifampicin (51.6%) therapy. Pruritus symptoms were assessed on a 5-point ordinal response scale, with scores ranging from 0 (none observed/reported) to 4 (very severe). To be included in the trial, participants had an average pruritus score of at least 1.5 in the 4 weeks prior to baseline. These patients were randomly assigned to receive oral maralixibat 570mcg/kg (n=33) or placebo (n=31) twice daily. 

Pruritus symptoms were reported by the patient’s caregiver twice daily on the Itch Reported Outcome Instrument (ItchRO[Obs]). Results showed treatment with maralixibat met the primary endpoint demonstrating a statistically significant difference from placebo in pruritus symptoms based on the mean change in average morning ItchRO(Obs) pruritus severity score between baseline and weeks 15 to 26 (mean difference from placebo, -1.2 [95% CI, -1.7, -0.7]; P <.0001).

The most common adverse reactions reported were diarrhea, fat soluble vitamin deficiency, abdominal pain, liver test abnormalities, hematochezia, and bone fractures.

“Livmarli’s approval in cholestatic pruritus for patients with PFIC is a result of years of investigation and a collection of a strong body of clinical evidence showing meaningful improvements across a number of important parameters, including pruritus, affecting children with PFIC,” said Richard Thompson, professor of molecular hepatology at King’s College London and an investigator in the MARCH study. “I am pleased that we will have a well-studied and efficacious option to offer patients whose life has been disrupted by itch.”

Livmarli is supplied as an oral solution containing 9.5mg of maralixibat per mL in a 30mL bottle. Mirum Pharmaceuticals is also seeking approval from the FDA for a higher concentration formulation (used during the MARCH study) for patients with PFIC.

Livmarli is also approved for the treatment of cholestatic pruritus in patients 3 months of age and older with Alagille syndrome.