Livmarli approved in Japan as itching treatment for Alagille, PFIC
Oral medication expected to have 'meaningful impact' on patients' lives
Livmarli (maralixibat) has been approved in Japan for the treatment of itching in people with Alagille syndrome and progressive familial intrahepatic cholestasis (PFIC), making it the first treatment available for these indications in the country.
The medication will be commercialized by Takeda Pharmaceuticals under an exclusive licensing agreement with Livmarli’s developer Mirum Pharmaceuticals. Takeda submitted the application seeking Livmarli’s approval to Japanese regulators last summer.
The therapy already is approved in more than 40 countries for treating Alagille and in more than 30 for use in PFIC. Livmarli is cleared for both indications in many of these regions, including in the U.S. and the European Union. Its developer welcomed the medication’s approval as an itching treatment for patients in Japan.
“We are thrilled to see Livmarli approved as the first and only medication available in Japan for patients living with pruritus [itching] related to [Alagille syndrome] and PFIC,” Chris Peetz, Mirum CEO, said in a company press release. “We are confident that Livmarli could have a meaningful impact on the lives of patients with [Alagille] and PFIC in Japan.”
Livmarli already approved as itching treatment in over 30 countries
Alagille syndrome is a rare genetic disease that can lead to a wide range of developmental problems and associated symptoms. Most people exhibit a reduced number of bile ducts in the liver, known as intrahepatic bile duct paucity.
The bile ducts are responsible for transporting the digestive fluid bile from the liver to the intestines. When there are problems with them, bile flow is slowed or stalled, known as cholestasis.
Bile subsequently accumulates in the liver, which can seriously harm the organ. It also backs up into the bloodstream, which is what is believed to drive the intense itching that characterizes Alagille and other liver diseases marked by cholestasis.
Another such disease is PFIC, in which genetic mutations interfere with proper bile transport out of the liver.
Livmarli is a liquid oral therapy designed to block the ileal bile acid transporter, or IBAT, which normally helps recycle bile acids in the intestines back to the liver. By suppressing IBAT, Livmarli aims to promote bile clearance through the intestines, thus lowering its levels in the bloodstream and easing pruritus.
In the U.S., where it’s marketed by Mirum, Livmarli is cleared for treating people with Alagille, ages 3 months and older, and for those with PFIC, ages 1 year and older. In the EU, it’s approved for individuals with Alagille, 2 months and older, and for PFIC patients 3 months and older.
[Takeda, which will market Livmarli in Japan, has] demonstrated success in the development and commercialization of medicines for rare diseases.
In Japan, the therapy will be marketed by Takeda under the licensing agreement.
According to Peetz, the company has “demonstrated success in the development and commercialization of medicines for rare diseases.”
Data from clinical trials involving people with Alagille generally showed that the treatment effectively eased pruritus and reduced bile acids in the bloodstream. Other analyses suggested the treatment has sustained clinical benefits with the potential to prolong survival and prevent liver-related clinical events.
Mirum is now sponsoring an observational registry study called LEAP (NCT06193928) that’s designed to monitor long-term outcomes for people with Alagille who have been prescribed Livmarli. That study is recruiting about 50 participants at U.S. sites.
Meanwhile, a Phase 3 clinical trial called EXPAND (NCT06553768) is evaluating the effects of Livmarli against a placebo in a broader group of people with cholestatic liver diseases and pruritus, The participants in that study are individuals who have failed to respond to other therapies and don’t have other treatment options.
The study is seeking 90 participants, ages 6 months and older, at sites worldwide, with the main goal of assessing the treatment’s effects on pruritus severity. The study is not enrolling people with Alagille, PFIC, intrahepatic cholestasis of pregnancy, primary biliary cholangitis, or primary sclerosing cholangitis who have not undergone a liver transplant.
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