Pam Vig, PhD, Head of Research and Development at Mirum Pharmaceuticals, discusses Alagille syndrome and progressive familial intrahepatic cholestasis (PFIC).
Transcription:
I’m Pam Vig, head of Research and Development at Mirum Pharmaceutical. We are a biotech company based in the Bay Area specializing in rare diseases. The company has been going for roughly about five years now, and we have an approval for Livmarli (maralixibat chloride) for cholestatic pruritus for patients with Alagille syndrome and have read out a phase three study in progressive familial intrahepatic cholestasis and currently running a study in biliary atresia. All these three are cholestatic liver diseases.
The mechanism of action of our first compound of Livmarli is that it is an IBAT inhibitor, and it essentially reduces bile acid systemically and intrahepatic ally by interrupting the intrahepatic circulation, meaning that for you and I our bile acids go round and round several times a day. In patients with cholestasis, they’re unable to remove those bile acids, get them out of the liver and into the gut. What this does is it stops the recirculation of those bile acids, and thereby lowering that systemic pool of bile acids and improving the symptoms and also improving long-term outcomes as we’ve seen in some of our long-term data.
As I mentioned, both are genetic diseases, but Alagille syndrome and PFIC differ. They’re both driven by elevated serum bile acids because there is an inability of bile acids to get out of the liver. Bile acids are very toxic in the liver. They’re not supposed to sit there. What happens is it drives inflammation, it drives disease progression, drives fibrosis, and it drives these very burdensome symptoms in these children. I’ll give you an example.
The Alagille and PFIC patients suffer from very debilitating pruritus or itch. Because of this, they will often require a liver transplant for that symptom. Just imagine that it’s so bad that they need a new liver, even in the absence of disease progression. They suffer from poor quality of life, failure to thrive. They’re under the growth curves. They don’t sleep. The family dynamic is very, very difficult. School is problematic, behavior becomes problematic. Ultimately, because it’s unbearable, these patients will go on to receive a liver transplant.
That’s the setting in both Alagille and PFIC, although for different reasons, they have an issue with the bile acids being elevated.
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