SLC10A2

Welcome to our podcast today, which is a medication review of linorixabat, a targeted ileal bile acid transporter, or IBAT.

My name is Christina Hansen, and I am a nurse practitioner at South Denver Gastroenterology and a board member of GAP.

I am joined today by my colleague, Dr. Marcelo Kugelmas, who serves as the Director of Hepatology and Research at South Denver GI and is also a board member for the Chronic Liver Disease Foundation.

Yeah, happy to.

So Lenorexibat, it's an ileal bile acid transporter inhibitor.

So we call this an IBAT inhibitor.

It's minimally absorbed in the gut and it interrupts the enterohepatic circulation of bile acids by inhibiting reabsorption in the ileum, therefore promoting their excretion in feces and thereby lowering circulating bile acids and other mediators linked to itch.

In Phase II studies, including Glimmer, Lenarixabat demonstrated a significant dose-dependent reduction in pruritus in the per-protocol population.

We had a small group of patients who were already on iBAT inhibitors, and we used the MDM as a way to make sure we were using this correctly.

And generally, we recommended that individuals continued with iBAT inhibitors.

But in another group with difficult to control pruritus, after putting together their genetic findings and their clinical picture, we were then able to potentially access IBAT inhibitors for either chronic cholestatic pruritus or to be used if they have future acute episodes.

And then this slide is slightly confusing, but in about a third of our patients, we identified variants where we didn't think they were contributing to the phenotype.

So that's where, yes, we found a variant, but we weren't convinced it was actually the underlying variant.

Do you know mutations or fixed subtypes that do not respond to an IBAD?

Well, this is a very nice and interesting question.

I showed you some of the results on surgical biliary diversion because we, in the real beginning, were very close to try to compare surgical biliary diversion to IBAT inhibition, so to pharmacological IBAT inhibition.

Today, we're also very excited to welcome our two guests, Dr. Tim Mitchell from Royal Perth Hospital and Professor James O'Byrne from the Sunshine Coast University Hospital.

In this episode, we'll be discussing unexplained cholestasis in adults, focusing on progressive familial enterohepatic cholestasis, or PFIC, and talking about IBAT inhibitors.

Welcome to the podcast, Dr. Mitchell and Professor O'Byrne.

Thanks for having us.

It takes a long time and it's really only relevant if you then want to screen a whole family.

And now moving on more to the management of PFIC, Professor O'Byrne, where do iBAT inhibitors fit in and who qualifies on the PBS?

So, well, I mean, IBAT inhibitors have revolutionized the treatment of this condition, and they've shown, certainly in children, to delay liver-related events and delay the need for liver transplantation.

And essentially, the way to think about IBATs is a medical way of biliary diversion.