FDA shoots down Mallinckrodt's redemption attempt, spurns rare kidney disease drug for a second time
Whatever hope Mallinckrodt had following a narrow recommendation by the FDA advisory committee to approve terlipressin has been dashed by a firm rejection.
The complete response letter stabbed right through the UK drugmaker’s case for the drug, as regulators are asking for “more information to support a positive risk-benefit profile for terlipressin” as a treatment of the rare kidney disease known as hepatorenal syndrome type 1, or HRS-1.
This is the second time regulators are spurning the drug, which got a fast track designation in 2005 only to be rejected in 2009. Soon afterwards its original developer, Orphan Therapeutics, out-licensed North American rights to Ikaria Therapeutics, which Mallinckrodt acquired in 2015.
Disappointed, Mallinckrodt CSO Steven Romano said his team stands by the data from the Phase III CONFIRM study, “the largest clinical trial ever conducted in this rare condition” involving 300 patients.
“HRS-1 is a complex disease that affects a critically ill patient population with no approved treatment in the U.S. at present,” he added in a statement. “We are surprised by and disagree with the FDA’s decision and remain committed to pursuing all available options as we continue working with the FDA toward approval of terlipressin in order to help address this difficult and life-threatening syndrome.”
Just a year ago, Cowen analysts hailed the positive data as a “key success” for embattled Mallinckrodt, which was facing a litany of failures for its acquired pipeline while under a cloud of opioid litigation and lawsuits targeting “ill-gotten gains” from Acthar, its cash cow.
Today the CRL counts as “yet another setback” in SVB Leerink analyst Ami Fadia’s eyes.
“We note that despite the overall positive vote, in our view the tone of the AdCom discussion was decidedly cautious, struggling to balance the high-unmet need with no currently available treatment options with concerns about lack of clinical benefit and an uncertain risk mitigation plan,” she wrote.
On the efficacy front, the FDA’s (and some of the outside experts’) chief concern was that the primary endpoint — which terlipressin met — was a surrogate endpoint that measures creatinine levels in blood. But it was unclear whether that led to clinical improvements for HRS-1 patients, who were characterized by cirrhosis and could develop life-threatening kidney failure within days.
More importantly, more patients died in the drug arm than in the placebo arm. And the FDA wasn’t satisfied with the risk mitigation strategy that Mallinckrodt offered. There was, however, “no clear outline on what would be considered sufficient for approval,” Fadia pointed out.
After much deliberation in July, the Cardiovascular and Renal Drugs Advisory Committee voted 8-7 for approval. Paul Ridker, a cardiologist at Brigham and Women’s Hospital and one of the panelists, said he voted yes but also wrote in “but barely.”
Approved in Europe under the brand name Glypressin, terlipressin now faces an uncertain future in the US.
Mallinckrodt, which has hinted at a potential bankruptcy filing, didn’t specify what the next steps will be. Investors sent the stock $MNK down 11.62%, edging close to penny-stock territory at $1.06.