PBC Approval | SKYE Update

Lickety-Split Analytics

Good Morning. Today we will be discussing a newly approved drug for the treatment of PBC and giving an update on Skye Biosciences following the discontinuation of one of their clinical programs.

-Ashley Adams

FDA Approves Ipsen’s PBC Therapy

On Monday, the FDA granted accelerated approval of Ipsen’s oral tablet formulation, Iqirvo (elafibranor), for the treatment of primary biliary cholangitis (PBC).

This approval is significant as PBC treatments have been limited to only two options, ursodeoxycholic acid (UDCA) approved in 1997 and obeticholic acid (OCA) approved in 2016.

PBC is a rare autoimmune disease, that typically affects mostly women. Researchers estimate the disease is present in about 65 out of 100,000 American women. PBC is characterized by inflammation in the bile ducts that damage the tissues. The body creates scar tissue called fibrosis to help repair this damage. When excessive fibrosis builds up, it blocks the flow of bile from the liver and leads to the accumulation of toxins in the liver. Fibrosis can build up in the liver and further impair liver function.

In a 2023 study, around 40% of PBC patients did not respond to UDCA at 1 year, leading to a worse prognosis. Later stage PBC can show similar symptoms as NASH and other liver diseases with decompensation events, like accumulated fluids being pushed out into the abdomen (ascites) and the bleeding of enlarged veins (varices), heavily contributing to mortality. The FDA approved Iqirvo based on its ability to reduce alkaline phosphate (ALP). Elevated alkaline phosphate (ALP) levels are thought to contribute to incomplete responses in patients taking UDCA.

Iqirvo is a dual peroxisome proliferator-activated receptor (PPAR) alpha/delta agonist. The mechanism is still being studied, but the activation of PPAR proteins is thought to help with fat metabolization, decreased inflammation, and protection of cells. It might be interesting to note, a similar PPAR candidate, lanifibranor, is being studied in a phase 3 NASH trial by Inventiva Pharma (IVA).

Iqirvo is currently approved for use in combination with UDCA in adults with inadequate response to UDCA or as a monotherapy in patients unable to tolerate UDCA. The drug is required to complete confirmatory trials to maintain approval.

Skye Biosciences Discontinues Glaucoma Candidate

On Monday, Skye Biosciences announced that they will discontinue development of their glaucoma candidate, SBI-100.