Takeda’s attempts to extend the uses of its multiple myeloma therapy Ninlaro into new disease areas have been hit by a failed phase 3 trial in amyloid light-chain amyloidosis (AL).
Ninlaro (ixazomib) plus dexamethasone failed to achieve a significant increase in overall haematological response compared to physician’s choice treatment in the TOURMALINE-AL1 trial, which involved patients with relapsed or refractory AL – also known as primary amyloidosis.
A readout on a secondary outcome measure – organ deterioration or death – hasn’t yet been reached but Takeda has decided to discontinue the trial regardless as the chances of a positive outcome are deemed to be slim.
AL is a rare disease that leads to the widespread build-up of amyloid deposits in tissues and organs outside the central nervous system, and results from abnormal plasma cells in the bone marrow. It’s an incurable disease, with symptoms currently managed using combination chemotherapy designed to kill off the aberrant plasma cells.
Takeda had hoped that Ninlaro – an orally-active proteasome inhibitor – would provide the first alternative to chemo for patients with AL.
Takeda chief executive Christophe Weber said last month that the company has already dialled down its sales expectations for Ninlaro in oncology to the $1.5bn-$2bn range, mainly because of increasing competition in the myeloma market.
Phil Rowlands
“While we are disappointed with this outcome, we aim to maximise 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,” said Takeda’s head of oncology Phil Rowlands.
The company will continue to study Ninlaro “across the continuum of multiple myeloma care,” he added.
It’s not the first setback for Ninlaro. Takeda had been closing in on a maintenance indication for Ninlaro in post-stem cell transplant myeloma patients after reporting progression-free survival (PFS) data from the TOURMALINE-MM3 phase 3 trial last year, but that was knocked back by the FDA with a request for overall survival (OS) data.
The filing has since been withdrawn as Takeda doesn’t yet have the number of fatalities in the study needed to give a reliable statistical analysis of OS.
On the plus side, Takeda has another trial scheduled to generate results later this year in newly-diagnosed patients, which if positive could move the drug from second- to first-line use.