Ailing Mallinckrodt's drug for rare, life-threatening renal condition clears pivotal study
Embattled Mallinckrodt — tarnished by a cloud of opioid litigation as well as its controversially expensive Acthar gel — will enjoy its sliver of optimism that comes with a positive pivotal trial.
The UK drugmaker on Thursday unveiled data from a late-stage trial testing the drug, terlipressin, in patients with a life-threatening, progressive rare complication of liver disease that triggers kidney failure called hepatorenal syndrome type 1 (HRS-1), which affects an estimated 30,000 to 40,000 in the United States each year, the company said, adding that patients face a poor prognosis, with a median survival time of less than two weeks and more than 80% mortality within three months.
Patients with HRS experience a constriction of the blood vessels that feed the kidneys, which leads to decreased blood flow to the organs, eventually impairing their function. The only curative therapy for patients is a liver transplant, which is intended to also fix the associated impaired kidney function — but the procedure does not guarantee that, and some patients permanently require dialysis, or worse, a kidney transplant. In addition, limited donors and long waiting lists make the transplant option not the most feasible alternative.
Terlipressin is engineered to activate vasopressin (also called antidiuretic hormone) and is commonly used in different indications, particularly in patients with end-stage liver disease. The compound is currently approved in Europe for hepatorenal syndrome as well as bleeding esophageal varices, under the brand name Glypressin, and is manufactured by Swiss specialty pharmaceutical drugmaker Ferring Pharmaceuticals.
Mallinckrodt’s $MNK CONFIRM trial tested the compound in 300 patients, and the study met the main goal of verified HRS-1 reversal (p=0.012) — an endpoint that constitutes three components: renal function improvement, avoidance of dialysis and short-term survival.
Detailed data will be presented at a medical conference, the company said, adding that it plans to submit a US marketing application early next year.
“(T)his is a key success for its acquired pipeline when up until today, several assets including stannsoporfin (discontinued), VTS-270 (failed Phase 3, but still in discussions with FDA) and CPP-1X/sulindac (discontinued) all failed to hit the mark,” Cowen analysts wrote in a note.
Apart from terlipressin, Mallinckrodt is also expecting late-stage data on its skin graft stratagraft in the coming months.
“Management has pegged the peak global opportunity at >$300M, and noted that along with Stratagraft this could more than offset the loss-of-exclusivity (LOE) impact from Ofirmev in the outer years,” the analysts added.
As part of its second-quarter results earlier this month, Mallinckrodt disclosed that it had suspended plans to spin off its specialty generics business, citing “current market conditions and developments, including increasing uncertainties created by the opioid litigation.” It also said it expects Acthar sales to generate less than $1 billion in 2019 sales, citing ongoing uncertainty.
Apart from its purported involvement in the opioid crisis, the Staines-upon-Thames-based company has long elicited the ire of regulatory agencies and the industry related to Acthar, which is manufactured via extraction from the pituitary glands of slaughtered pigs —essentially the same way as it was when it was first discovered in the late 1940s.
However, the drug’s price has catapulted from $40 per vial in 2001 to a whopping $38,892. In a lawsuit filed earlier this month, health insurer Humana said it was seeking to recoup from Mallinckrodt “ill-gotten” gains.
The Federal Trade Commission — along with the states of Alaska, Maryland, New York, Texas and Washington — alleged Mallinckrodt had taken advantage of its monopoly to repeatedly raise the price of Acthar and acquired the rights to its greatest competitive threat to keep competition at bay, the company agreed in 2017 to part with $100 million to settle those charges. This June, the US Department of Justice joined two whistleblower lawsuits in alleging that the company used a foundation as a conduit to pay illegal kickbacks in the form of copay subsidies for Acthar so it could market the drug as “free” to doctors and patients while increasing its price between 2010 and 2014.