Mallinckrodt’s Phase III Kidney Failure Trial Hits Primary Endpoint
Executive Summary
The data position Mallinckrodt to file for US FDA approval of terlipressin early next year. Mallinckrodt thinks the drug could generate sales of $300m a year, helping it to mitigate its challenges.
A Phase III trial of Mallinckrodt PLC’s terlipressin in adults with a type of progressive kidney failure has hit its primary endpoint.
The study enrolled 300 patients with hepatorenal syndrome type 1 (HRS-1) and randomized them to receive intravenous delivery of vasopressin analogue terlipressin or placebo. Subjects who received the experimental therapy were significantly more likely to experience HRS-1 reversal, as defined by improved renal function, avoidance of dialysis and short-term survival.
That resulted in the trial hitting its primary endpoint, although Mallinckrodt is yet to reveal just how effective terlipressin was in the study. The only number released by Mallinckrodt to date is the 0.012 p value associated with the primary endpoint of HRS-1 reversal. The trial also met “nearly all” of the prespecified secondary endpoints.
The results are a rare piece of good news for Mallinckrodt. On the R&D front, the firm has suffered from the discontinuation of stannsoporfin and CPP-1X/sulindac, plus the Phase III failure of VTS-270.
Perhaps more critically, Mallinckrodt faces ongoing US opioid litigation, the uncertainty surrounding which recently led it to suspend plans to spin off its specialty generics business, and is facing separate legal cases and reimbursement challenges related to its best-selling drug, Acthar. The combined weight of these problems overshadowed the Phase III results, as was predicted by analysts.
“While we acknowledge that the investor reaction to this event is likely to be muted given these larger, near-term headwinds, this is nevertheless a step in the right direction as management looks to evolve the business. We also see this as an important win for management's ability to execute on its pipeline,” analysts at SVB Leerink wrote in an investor note. BMO Capital Markets analysts expressed similar sentiments.
Faced with the problems, Mallinckrodt is forging ahead with efforts to add growth drivers to its product portfolio. Mallinckrodt plans to file for approval in the US early next year, capping off terlipressin’s long journey back to the Food and Drug Administration.
Orphan Therapeutics sought FDA approval of terlipressin a decade ago on the strength of data from a Phase III trial that missed its primary endpoint. The FDA issued a complete response letter to the company in 2009, leading to the acquisition of the North American rights by Ikaria the following year. Ikaria began a Phase III trial, which also missed its primary endpoint, before selling up to Mallinckrodt in 2015.
Mallinckrodt’s $2.3bn takeover of Ikaria centered on INOmax, a drug to improve blood oxygen levels, but the company also acquired terlipressin and, after talking to FDA, decided to run the Phase III trial that read out this week. The top-line data suggests that decision has paid off.
The readout is the first of two near-term clinical catalysts for Mallinckrodt. The second will come when Mallinckrodt has data from a pivotal trial of StrataGraft skin tissue in patients with deep partial thickness burns. Mallinckrodt has begun preparing to start commercializing the two products.
“StrataGraft and terlipressin will largely be in the hands of our existing sales team that's currently selling Ofirmev. A year or so ago we started to position that sales team and target them in a way that was appropriately sized and appropriately targeted for the introduction of these new products. We're in very good shape in terms of the launch preparations,” Mallinckrodt CEO Mark Trudeau said on a quarterly results conference call with investors earlier this month.
Mallinckrodt needs sales of the products to ramp up quickly given the pressures on other parts of its business. A key patent on Ofirmev, an injectable pain treatment that generated sales of $342m last year, is set to expire in 2021. Perrigo Co. PLCis cleared to introduce a generic copy of the drug shortly before the intellectual property protection ends.
The arrival of generic competition is likely to eat into Ofirmev sales. By then Mallinckrodt hopes to have StrataGraft and terlipressin on the market and leveraging the commercial infrastructure that is used today to sell Ofirmev.
Mallinckrodt thinks terlipressin could achieve peak sales in excess of $300m, reflecting the fact there are currently no approved drugs for the estimated 30,000 to 40,000 people affected by HRS-1 in the US each year. When StrataGraft is factored in, Mallinckrodt expects revenues from the new products to exceed peak sales of Ofirmev.