FDA Greenlights First and Only Treatment for Cholestatic Pruritus with ALGS

Cholestatic pruritus with Alagille syndrome (ALGS) is a rare disease that affects 2000 to 2500 children in the US, with an estimated incidence of one in every 30,000 people. The genetic disorder is induced by malformed or reduced bile duct, leading to the accumulation of bile acids in the liver and causing liver inflammation and injury. Signs and symptoms arising from liver damage in ALGS may include jaundice, xanthomas, and pruritus. The most common way to treat is to seek opportunities for liver transplantation.

On September 29th, the FDA greenlit Mirum Pharmaceuticals’ Livmarli (maralixibat) as the first and the only approved therapy for this condition to treat patients at the age of one or older. Livmarli is an orally administered, minimally absorbed ileal bile acid transporter (IBAT) inhibitor. It inhibits the apical sodium dependent bile acid transporter (ASBT), which results in more bile acids excreted in the feces. This relatively reduces the degree of bile acid accumulation in the liver. In conjunction with the approval, Mirum received a rare pediatric disease priority review voucher.

“Children with Alagille syndrome suffer from cholestatic pruritus, which is serious, unremitting, and debilitating. Their sleep is disrupted, and they endure bleeding and scarring of the skin due to unrelenting scratching,” said Binita M. Kamath, MBBChir, Pediatric Hepatologist, The Hospital for Sick Children (SickKids), Toronto, Ontario, Canada. The approval, according to Kamath, is a blessing to the young victims.

ICONIC Clinical Study

The FDA approval of Livmarli is an outcome of the pivotal ICONIC clinical trial, in addition to the five years of supportive data. The study demonstrated a statistically significant long-lasting reduction in pruritus, one of the most common and refractory symptoms associated with the disease; the reduction was maintained over the course of four years.

“We have had the pleasure of being part of and closely following the clinical progress of Livmarli in many ways. Since the first study’s initiation more than a decade ago, we have dreamed of today, seeing Livmarli receive FDA approval, marking an incredibly meaningful milestone for the ALGS community,” said Roberta Smith, President, Alagille Syndrome Alliance and an ALGS mom.

Smith continued, “until now, patients have had limited-to-no treatment options to address the severe and unrelenting itch that significantly impacts both patients and their families. Additionally, because pruritus associated with ALGS greatly impacts caregivers, having a strong support program like Mirum Access Plus to reduce the strain on families is so important. The ALGS community has been waiting for a long time for a treatment and we’re so pleased that Livmarli is now available in the United States.”

Safety evaluations suggest that Livmarli is generally well-tolerated throughout the studies. The most frequent treatment-related adverse events are diarrhea and abdominal pain.

Author

Judy Ya-Hsuan Lin

Success is the ability to go from one failure to another with no loss of enthusiasm.