Takeda swings and misses with Ninlaro in AL amyloidosis, calls off phase 3 trial

With its once-biggest seller Velcade bracing for generic competition, Takeda has big plans for its oral multiple myeloma drug Ninlaro. But now, the med has suffered two setbacks in the span of a few months. After Ninlaro hit a snag at the FDA in an expanded use back in February, the company this week canned a phase 3 trial in another rare disease.

Ninlaro had been in phase 3 testing for patients with systemic light-chain amyloidosis, but an analysis showed the med didn't meet a primary endpoint. Investigators were testing a combo of Ninlaro and dexamethasone in patients who'd relapsed or failed to respond to another treatment. Compared with a doctor’s choice of standard chemotherapy, Ninlaro didn’t improve overall hematologic response, so Takeda called the trial off. 

In patients with the disease, certain plasma cells produce abnormal immunoglobulin light-chain fragments. Patients develop amyloid deposits in organs and tissues, particularly the kidneys, heart, liver and nerves, Takeda said. That, in turn, can lead to organ failure and death.

Takeda’s oncology head Phil Rowlands said in a statement the company is “disappointed" with the result, but still aims to “maximize our learnings from this trial and share findings with the community in hopes of helping to improve care for patients living with this devastating disease.” The Ninlaro study was “one of the largest studies ever conducted in systemic light-chain AL amyloidosis and we are proud to have led it,” Rowlands added.

Ninlaro’s trial failure comes after the company in February withdrew a multiple myeloma maintenance application at the FDA to await more survival data.

Since its 2015 approval, Ninalaro has been a growth engine at the drugmaker, posting a 34% sales increase last year to 62.2 billion yen ($575 million). A follow-up to Velcade, Ninlaro is approved in combo with Revlimid and dexamethasone to treat multiple myeloma patients who've received at least one prior therapy. Fresenius Kabi launched its own version of Velcade last year, and though it's not a true generic, the Takeda med's sales slumped during the company's 2018 fiscal year.

Aside from its approved use, Takeda is testing Ninlaro in newly diagnosed multiple myeloma and as a maintenance therapy in certain multiple myeloma patients.  

Back in 2017, Takeda CEO Christophe Weber said Ninlaro stands to be a “significantly bigger” opportunity than Velcade, with potential peak sales of $3 billion. As 2018’s results show, the company has a ways to go to meet that goal.