The FDA approves Iqirvo (elafibranor) for primary biliary cholangitis (PBC) treatment, offering a new option for patients intolerant to UDCA.
What is Primary Biliary Cholangitis (PBC)?
A case study from December 2023 reports a 19-year-old male with multiple congenital abnormalities and an intellectual disability suffered from pruritus for 5 years. Tests revealed elevated levels of liver enzymes, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase, indicating liver damage. After excluding more common causes, such as viral hepatitis, alpha-1 antitrypsin deficiency, Wilson’s disease, and other genetic cholestatic liver diseases, clinicians performed a liver biopsy and found the underlying cause to be the rarer autoimmune disease, primary biliary cholangitis (PBC).
PBS is a chronic autoimmune liver disease where the bile ducts in the liver are gradually destroyed by T-cell lymphocytes, causing bile to accumulate and triggering a cascade of inflammation and scarring. The disease is caused by both genetic predisposition and environmental triggers. It typically manifests in both male and female between 35 and 60 years old. According to a recent report, PBC is as rare as 14.60 cases per 100,000 persons
Current treatments
While there is no known cure for PBC, early intervention with medications can slow the progression of liver damage, offering a glimmer of hope in an otherwise challenging journey. Ursodeoxycholic acid or UDCA (Actigall, Urso) is the main treatment for PBC, as it helps with the recovery of liver damage by helping to move bile through the liver, if administered at an early stage.
UDCA is often used with the combination of other drugs, such as Obeticholic acid (Ocaliva, Intercept Pharmaceuticals, Inc.), corticosteroids like Budesonide, or Fenofibrate (Tricor) to reduce the liver fibrosis. Although, all the combination treatments are targeted to the treat the symptoms and comes with their own side effects. When medicine cannot help anymore, liver transplant seems to be the only viable option.
How does Iqirvo work?
Iqirvo is a first-in-class oral, dual peroxisome proliferator-activated receptor (PPAR) agonist that acts on the root cause of the disease rather than the symptoms. On 10th June the FDA approved Iqirvo to be used as a combinatorial therapy for the PBC treatment along with ursodeoxycholic acid (UDCA) in adults who respond poorly to the monotherapy. It activates PPAR-alpha and PPAR-delta, which subsequently induces Fibroblast Growth Factor 21 (FGF21)-dependent downregulation of CYP7A1, the key enzyme for the synthesis of bile acids from cholesterol.
Clinical Studies, Efficacy and and Side Effects
ELATIVE, the clinical trial for Iqirvo is a multi-center, randomized double-blind, placebo-controlled Phase III trial conducted in 161 participants. The trial determined the efficacy and side effects of the drug for 52 weeks in 108 patients who have been administered the drug with UDCA and 53 participants who received placebo along with UDCA. The drug and placebo were also used as a monotherapy for patients intolerable to UDCA.
The biochemical response was defined by a combination of factors, including ALP levels and total bilirubin within the normal range at week 52. The trial showed that Iqirvo significantly outperformed the placebo, with 51% of patients achieving a biochemical response compared to just 4% on the placebo, resulting in a remarkable 47% treatment benefit. The trial also demonstrated that Iqirvo’s biochemical response was rapid, with significant reductions in ALP levels seen as early as week 4 and sustained through week 52. Common side effects experienced by ≥10% of participants included weight gain, abdominal pain, diarrhea, nausea, and vomiting.
Future of the battle against RSV With this historic milestone achieved, medical science approaches a step closer to the treatment of such a rare liver disease. While the drug has not been shown to improve survival or prevent liver decompensation, it has been shown to improve biochemical response in patients with PBC. Iqirvo is the first new treatment for PBC in nearly a decade and offers new hope for patients with this disease.
Dr. Avraneel Paul, Ph.D.
Sources
- https://www.frontiersin.org/articles/10.3389/fped.2023.1280409/full
- https://journals.lww.com/hepcomm/fulltext/2023/06010/primary_biliary_cholangitis__epidemiology,.27.aspx
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218860s000lbl.pdf
- https://clinicaltrials.gov/study/NCT04526665#xd_co_f=NjM2ZGY3NjUtNmY2Zi00Yzc5LWIwOTQtYWE5ZGQwNmVlYjA3~
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