FDA approves Livmarli oral tablets for PFIC, Alagille
Trial data show treatment eases pruritus, lowers bile acid
The U.S. Food and Drug Administration (FDA) has approved an oral tablet formulation of Livmarli (maralixibat) to treat progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome.
Livmarli, which has been available as an oral liquid formulation, is indicated in the U.S. for the treatment of itching, or pruritus, in PFIC patients 1 and older, and those with Alagille 3 months and older. The new tablets can be used for patients weighing at least 25 kg (around 55 pounds) who are able to swallow pills.
“The approval of Livmarli in tablet form provides a meaningful additional treatment option for patients with [Alagille] and PFIC,” Peter Radovich, president and chief operating officer at Mirum Pharmaceuticals, Livmarli’s developer, said in a company press release. “It allows flexibility for patients and physicians, with the liquid dosing used by the youngest patients and a convenient one-tablet per dose option for older patients.”
The company expects that the tablets, which will come in 10 mg, 15 mg, 20 mg, and 30 mg strengths, will be available in June through Mirum Access Plus, the company’s support program designed to facilitate access and insurance coverage for the oral therapy.
PFIC refers to a group of rare liver diseases caused by genetic mutations that interfere with the transport of the digestive fluid bile out of the liver, leading to stalled bile flow, or cholestasis. There are several PFIC types, each caused by mutations in different genes.
Easing cholestasis by getting rid of bile acids
In PFIC, bile builds in the liver, damaging it, and backs up into the bloodstream, leading to cholestasis symptoms such as pruritus. Alagille is a rare genetic disease that commonly affects the liver, leading to cholestasis and itching.
Livmarli is a cholestasis treatment designed to promote the excretion of bile acids, bile’s main components, in the feces, lowering their levels in the bloodstream and easing symptoms like itching. It does so by blocking a protein called the ileal bile acid transporter that usually recycles bile acids from the digestive tract back to the liver.
Clinical trial data have demonstrated Livmarli’s ability to ease pruritus and lower blood bile acid levels across PFIC types.
The recommended maintenance dose of Livmarli for PFIC, regardless of the formulation, is 570 micrograms per kilogram of body weight (mcg/kg), taken twice daily before a meal, and titrated up from a starting dose of 285 mcg/kg once daily. The maximum daily dose is 38 mg for the liquid formulation and 40 mg for the oral tablets.
As with the liquid formulation, Livmarli tablets can be used across PFIC types, but are not recommended for a subgroup of PFIC type 2 patients who have rare mutations in the ABCB11 gene that lead to a nonworking or completely absent bile salt export pump protein. These mutations make the therapy useless in these cases.
The therapy is not recommended for patients who have had clinical complications related to liver decompensation, when the liver fails to keep up with its usual functions.
“We have had tremendous success with Livmarli since its launch and we hope that the availability of the tablet will provide convenience that positively impacts patients’ lives,” Radovich said.
Beyond its U.S. approvals, the liquid formulation of Livmarli is approved in countries including Japan and countries of the European Union to treat PFIC and Alagille, although the indicated age ranges vary.
The ongoing Phase 3 EXPAND clinical trial (NCT06553768) is also evaluating the possible benefits of Livmarli in people with other types of cholestatic liver diseases and related pruritus for whom treatments are lacking or ineffective.
The trial is enrolling participants ages 6 months and older at sites globally, but will not include people with PFIC, Alagille, intrahepatic cholestasis of pregnancy, primary biliary cholangitis, or primary sclerosing cholangitis who have not undergone a liver transplant.
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