New drug for rare liver diseases! EU CHMP recommends approval of Livmarli: Treatment of cholestatic itching associated with Alagille syndrome (ALGS)!

Livmarli is the first drug
approved for the treatment of cholestatic pruritus in ALGS.
It is an oral apical sodium-dependent ileal bile acid transporter (ASBT) inhibitor that results in more bile acids being eliminated from the stool and reduces bile acid-mediated liver injury and complications
.

October 20, 2022 /BioValleyBIOON/ --Mirum Pharma is a biopharmaceutical company
dedicated to developing innovative therapies to treat rare liver diseases.
Recently, the company announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive review recommending the approval of Livmarli (maralixibat) oral solution: the drug is taken orally once daily for the treatment of cholestatic pruritus in patients older than 2 months of age with Alagille syndrome (ALGS
).
The European Commission (EC) will review the CHMP's comments and expect a final review decision
within the next 2 months.

In addition, Mirum announced that its partner Neopharm has received marketing authorization from the Israeli Ministry of Health: approval of Livmarli for the treatment of cholestatic pruritus in ALGS patients aged ≥ 1 year
.
This approval represents Livmarli's second regulatory approval globally and for markets outside the United States
.

In September 2021, Livmarli was approved by the US FDA for the treatment of cholestatic pruritus in ALGS patients aged 1 year and older
.
It is worth mentioning that Livmarli is the first drug approved for the treatment of cholestatic pruritus in ALGS, which will bring a meaningful shift
in the treatment model of ALGS.

ALGS is a rare and devastating inherited liver disease that affects 1 in 30,000 people worldwide
.
ALGS is caused by abnormalities in the bile ducts, which can lead to progressive liver disease
.
Abnormal or narrowed bile ducts can lead to cholestasis, where bile acids build up, leading to inflammation and liver damage, and preventing the liver from working properly
.
Cholestasis of ALGS is associated
with itching.
Pruritus is one of the most common and severe symptoms associated with ALGS and one of
the most common indications for liver transplantation in ALGS patients.

The active pharmaceutical ingredient of Livmarli oral solution is maralixibat, an orally administered ileal bile acid transporter (IBAT) inhibitor
with minimal absorption.
ALGS is a rare liver disease for which there is no recognized treatment, so there is a significant and urgent unmet medical need
.
The approval of Livmarli, which brings the first-ever drug treatment option for this devastating disease, will provide a meaningful treatment option that will ultimately reduce the need for
liver transplants.

The positive review opinion of the EU CHMP, based on data from key ICONIC studies, including more than 5 years of data from Livmarli's clinical program, together form a strong body
of evidence for Livmarli for the treatment of ALGS patients.
Data from the ICONIC study showed a statistically significant and clinically significant reduction in pruritus symptoms (mean difference: -1.
4 points, p<0.
0001) and serum bile acids in patients treated with Livmarli compared with placebo, both of which were sustained over several years of treatment
.
The CHMP recommended label also includes reducing xanthoma severity
.

Maralixibat's mechanism of action and chemical structure (Image source: drugfuture.
com)

Marialixibat, a novel, minimally absorbed, oral ileal bile acid transporter (IBAT) inhibitor, is being evaluated for
several rare cholestatic liver diseases.
Marialixibat inhibits apical sodium-dependent bile acid transporters (ASBTs), causing more bile acids to be excreted in the feces, leading to a decrease in systemic bile acid levels, potentially reducing bile acid-mediated liver injury and associated effects and complications
.

Alagille syndrome (ALGS) is a rare genetic disorder caused by abnormalities of the bile ducts (strictures, malformations, decreased number) that lead to a buildup of bile in the liver and eventually progress to liver disease
.
The incidence of ALGS is estimated at 1 in 30,000 people
.
In ALGS patients, multiple organ systems may be affected by mutations, including the liver, heart, kidneys, and central nervous system
.

The accumulation of bile acids prevents the liver from working normally to remove waste products from the blood, and according to recent reports, 60%-75% of ALGS patients receive a liver transplant
before adulthood.
Signs and symptoms of ALGS liver injury may include jaundice (yellowing of the skin), xanthelasma (deforming cholesterol deposits under the skin), and itching
.
The itching experienced by ALGS patients is the most severe of all chronic liver diseases and appears
at age 3 in most affected children.

In addition to ALGS, maralixibat is in late-stage clinical development for the treatment of other rare cholestatic liver diseases, including progressive familial intrahepatic cholestasis (PFIC) and biliary atresia
.
Previously, the U.
S.
FDA granted maralixibat breakthrough therapy designation (BTD) and orphan drug designation (ODD)
for the treatment of these three diseases.
(Bio Valley Bioon.
com)

Mirum Pharmaceuticals Announces Positive CHMP Opinion for LIVMARLI® (maralixibat) Oral Solution for Cholestatic Pruritus in Patients with Alagille Syndrome Two Months of Age and Older