For years, Mallinckrodt’s terlipressin has been the standard of care in Europe to treat the life-threatening condition hepatorenal syndrome (HRS) with rapid reduction in kidney function.
Satisfying regulators in the United States however has been a challenge. Twice in a span of 17 months, U.S. regulators rejected the drug. But on Wednesday, the FDA finally signed off on Terlivaz as the first approved treatment for the condition, which affects between 30,000 and 40,000 annually in the U.S.
If left untreated, HRS with rapid reduction in kidney function has a median survival time of two weeks. A majority of patients die within three months. The condition affects those with liver cirrhosis, constricting blood vessels in the kidneys and leading to a build up of toxins.
“Diagnosing and treating HRS can be challenging and every minute counts,” Steven Romano, M.D., Mallinckrodt’s chief financial officer, said in a release, adding that the approval will lessen the need for “renal replacement therapy, such as dialysis.”
With news of the nod, Mallinckrodt's stock had jumped 20% by mid-morning on Thursday. The approval came well ahead of the FDA's target date of December 9. The company said Terlivaz would be available in the U.S. within weeks.
In 2019, when Mallinckrodt appeared on the verge of a U.S. nod for the drug, analysts at Cantor Fitzgerald pegged its sales potential at $300 million in the U.S.
Used as a treatment for managing low blood pressure, with indications for septic shock and esophageal bleeding, terlipressin has been sanctioned in some countries for more than three decades.
But getting it across the FDA finish line has been a challenge for three companies. More than a decade ago, Orphan Therapeutics came up short in a phase 3 trial of terlipressin in HRS. Later, Ikaria did the same after buying the drug's rights in North America.
Then after Mallinckrodt bought out Ikaria in 2016, the FDA helped convince the Dublin-based company to take another swing at HRS.
In September of 2020, Mallinckrodt appeared on the verge of winning approval when an advisory committee voted 8-7 in favor of recommending a green light. A phase 3 trial had shown the benefit of the drug, but the FDA ultimately rejected terlipressin because of uncertainty of benefit over risk.
Once again, Mallinckrodt appeared to near an approval early this year after satisfying U.S. regulators with more trial data. But in February, Mallinckrodt determined it needed a new facility to package and label the drug, making it impossible that an FDA inspection could be accomplished before the agency’s approval date.
Now, the nod could help Mallinckrodt get out from under its financial problems. In 2021, Mallinckrodt agreed to a $1.7 billion settlement to resolve opioid claims while also undergoing Chapter 11 restructuring.