EMA Recommends to Refuse Marketing Authorisation for Ixazomib

It was expected to be used for treating multiple myeloma in adults who had received at least one prior treatment

On 26 May 2016, the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion, recommending the refusal of the marketing authorisation for the medicinal product ixazomib (Ninlaro), intended for the treatment of multiple myeloma.

The company that applied for authorisation is Takeda Pharma A/S. It may request a re-examination of the opinion within 15 days of receipt of notification of this negative opinion.

What is Ninlaro?

Ninlaro is a cancer medicine that contains the active substance ixazomib. It was to be available as capsules.

What was Ninlaro expected to be used for?

Ninlaro was expected to be used for treating multiple myeloma in adults who had received at least one prior treatment. Ninlaro was designated an ‘orphan medicine’ (a medicine to be used in rare diseases) on 27 September 2011, for the treatment of multiple myeloma. 

How was Ninlaro expected to work?

The active substance in Ninlaro, ixazomib, is a proteasome inhibitor. This means that it blocks the proteasome, which is a system within cells that breaks down proteins when they are no longer needed. When the proteins in the cancer cells are not broken down, including the proteins that control cell growth, the cancer cells are damaged and they eventually die.

What did the company present to support its application?

The effects of Ninlaro were first tested in experimental models before being studied in humans. The company presented results from one main study 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 the medicines lenalidomide and dexamethasone. The main measure of effectiveness was progression-free survival. 

What were the CHMP’s main concerns that led to the refusal?

The CHMP considered that the data from the main study were insufficient to demonstrate a benefit of Ninlaro in the treatment of multiple myeloma. The company 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. However, 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 authorisation.

What consequences does this refusal have for patients in clinical trials or compassionate use programmes?

The company informed the CHMP that there are no consequences for patients currently included in clinical trials or compassionate use programmes with Ninlaro.