Takeda's Ninlaro falls short in first line multiple myeloma

Takeda’s Ninlaro (ixazomib) has fallen short in a late-stage study testing it in combination with Bristol-Myers Squibb/Celgene’s Revlimid and chemo in newly diagnosed multiple myeloma.

The data from the TOURMALINE-MM2 study follows an announcement from BMS and AbbVie that their Empliciti also could not improve survival in the same indication when combined with Revlimid and chemo.

Both Takeda and BMS are hoping to compete against Johnson & Johnson’s Darzalex (daratumumab), which has gained a foothold in multiple myeloma and is generating blockbuster-level sales.

With Ninlaro, Takeda is trying a different approach to BMS – while Empliciti inhibits a receptor known as CS1, Ninlaro is a proteasome inhibitor.

The drug works by setting off a chain reaction that leads to the death of multiple myeloma cells, and has already been approved in previously treated multiple myeloma patients.

Moving the drug to the first line indication could unseat Darzalex, which is gaining a foothold in this patient group and works by targeting CD-38.

But Takeda said that in the 705-patient study in untreated patients ineligible for a transplant, adding Ninlaro to Revlimid (lenalidomide) plus dexamethasone improved median progression-free survival by 13.5 months compared with Revlimid and chemo alone.

Although the Ninlaro combination produced progression-free survival (PFS) of 35.3 months compared with 21.8 months with Revlimid and chemo, the results did not meet the threshold for statistical significance.

Safety-wise Takeda said there were no surprises with any side effects consistent with those seen in other trials of Ninlaro.

Investigators have been informed of the outcome and will discuss the potential impact with study participants.

For patients currently enrolled in this study, it is up to the discretion of doctors to continue their current treatment.

Key secondary endpoints of the study include rate of complete response (CR), pain response and overall survival (OS), but Takeda gave no details about whether these goals were met.