Takeda Oncology Hopes Hit By CHMP Ninlaro Rejection; Appeal Planned

An EMA advisory committee has set back Takeda Pharmaceutical Co. Ltd.’s oncology plans by rejecting Ninlaro as a treatment for multiple myeloma in the region, saying supporting data was inadequate for its backing but the Japanese company aims to appeal the decision.

Ninlaro (ixazomib), a drug Takeda is pinning its near-term oncology hopes on and which went on sale in the US in December, has been panned by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) due to insufficient proof of its efficacy.

The committee considered results from one main study submitted by Takeda involving 722 adults with multiple myeloma whose disease had not responded to or had come back after previous treatment. The study compared Ninlaro with placebo, both taken together with lenalidomide and dexamethasone. The main measure of effectiveness was progression-free survival.

Insufficient Proof

The advisory committee could not recommend the oral proteasome inhibitor based on that data, the EMA said in a statement issued May 27, adding: "The CHMP considered that the data from the main study were insufficient to demonstrate a benefit of Ninlaro in the treatment of multiple myeloma."

It said Takeda had proposed restricting the use of the medicine to patients whose disease is more difficult to treat and had come back after one previous treatment, and to those whose disease had come back after at least two previous treatments. But the committee rejected that idea, saying, "The data in these subgroups were not compelling enough and the rationale for assuming greater effectiveness in these patients was not clear. Therefore, the CHMP was of the opinion that based on the currently available data, the benefits of Ninlaro did not outweigh its risks and recommended that it be refused marketing authorization."

Takeda Not Happy

Takeda reacted with frustration, saying it will appeal the decision and request a re-examination by the CHMP.

“We are disappointed by the CHMP’s opinion. With the support of European key medical experts, we will continue our efforts working closely with the CHMP to make Ninlaro - the first oral proteasome inhibitor - available for patients in Europe,” said Christophe Bianchi, who heads oncology at Takeda.

"We stand behind the TOURMALINE-MM1 trial data, which were recently published in the New England Journal of Medicine and demonstrated a significant extension in progression-free survival for Ninlaro and lenalidomide and dexamethasone versus placebo and lenalidomide and dexamethasone and a favorable benefit-risk profile," he added.

In the US, Ninlaro was approved in November 2015 by the FDA for use in combination with Celgene's Revlimid (lenalidomide) and dexamethasone in multiple myeloma patients who have been treated with at least one prior therapy. Takeda currently has five Phase III studies ongoing in its Tourmaline program for Ninlaro. It hopes that data from three of those trials will help it secure a first-line use label.

Rising Competition In MM

The multiple myeloma treatment market is heating up, with rival therapies aside from Ninlaro including Johnson & Johnson/Genmab AS’ Darzalex (daratumumab), and Bristol-Myers Squibb Co.’s Empliciti (elotuzumab), all of which have reached the US market. Novartis AG’s Farydak (panobinostat), was approved by FDA in September as a third-line multiple myeloma therapy, though its use will likely be limited due to high toxicity.

The other backbone therapies in multiple myeloma are proteasome inhibitors, where Takeda/J&J’s Velcade (bortezomib) dominates the market. But competition in the category is building. Amgen Inc. is looking to develop a new leader: Kyprolis (carfilzomib), which launched in 2012 under then owner Onyx Pharmaceuticals Inc., acquired by Amgen in 2013