EMA Recommends Granting a Conditional Marketing Authorisation for Ixazomib

In combination with lenalidomide and dexamethasone, ixazomib is intended for the treatment of multiple myeloma after at least one prior therapy

On 15 September 2016, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending granting a conditional marketing authorisation for the medicinal product ixazomib (Ninlaro) for the treatment of multiple myeloma in adults who have received at least one prior treatment. This follows a re-examination of the Committee’s earlier negative opinion. Ninlaro is a new medicine that is taken orally. It was designated as an orphan medicinal product (a medicine to be used in rare diseases) on 27 September on 27 September 2011.

The applicant for this medicinal product is Takeda Pharma A/S.

Ninlaro will be available as 2.3, 3 and 4 mg hard capsules. The active substance of Ninlaro is ixazomib, a reversible proteasome inhibitor (ATC code: L01XX50).

The benefits with Ninlaro are its ability to delay the progression of multiple myeloma when used in combination with lenalidomide and dexamethasone.

The most common side effects are diarrhoea, constipation, thrombocytopenia, peripheral neuropathy, nausea, peripheral oedema, vomiting and back pain.

The full indication is:

“Ninlaro in combination with lenalidomide and dexamethasone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.”

It is proposed that treatment must be initiated and monitored under the supervision of a physician experienced in the management of multiple myeloma.

Detailed recommendations for the use of this product will be described in the summary of product characteristics, which will be published in the European public assessment report and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission.

On 26 May 2016, the CHMP had originally adopted a negative opinion for Ninlaro in multiple myeloma. At the request of the applicant, the CHMP started a re-examination of its opinion. Following the re-examination, the CHMP adopted a final positive opinion on 15 September 2016 recommending the authorisation of Ninlaro, conditional to the company providing further data to confirm the benefits.

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 (PFS).

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.

During the re-examination, the CHMP consulted a group of experts in cancer and considered, among other things, Ninlaro’s safety profile, the fact that it is taken by mouth, and the possibility of the company providing further data on the benefits of the medicine.

The CHMP agreed with the expert group’s conclusion that the available data from the main study indicate that Ninlaro improves patients’ PFS. As there is some uncertainty regarding the size of the improvement, further confirmatory data will need to be provided by the company as a condition for marketing authorisation. The Committee also acknowledged Ninlaro’s favourable safety profile and the convenience of patients taking the capsules at home. Therefore, the CHMP concluded that the benefits of Ninlaro outweigh its risks and recommended that Ninlaro be granted a conditional marketing authorisation.