Outcome of re-examination

London, United Kingdom (Announcement) – On 14 December 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion, recommending the refusal of the market­ing authori­sa­tion for the medicinal prod­uct Aplidin, intended for the treat­ment of multiple myeloma. The com­pany that applied for author­i­sa­tion is PharmaMar.

The com­pany requested a re-examination of the initial opinion. After con­sidering the grounds for this request, the CHMP re-examined the opinion, and con­firmed the refusal of the market­ing author­i­sa­tion on 22 March 2018.

What is Aplidin?

Aplidin is a cancer medicine that con­tains the active substance plitidepsin. It was to be avail­able as a powder and solvent to be made up into a solu­tion for infusion (drip) into a vein.

What was Aplidin ex­pec­ted to be used for?

Aplidin was ex­pec­ted to be used to treat adults with multiple myeloma (a cancer of the bone marrow) who have received at least three prior cancer treat­ments (including bor­tez­o­mib, and either lena­lido­mide or thalido­mide). Aplidin was to be used in com­bi­na­tion with dexa­meth­a­sone (another medicine used to treat multiple myeloma).

Aplidin was designated an ‘orphan medicine’ (a medicine to be used in rare diseases) on 16 Novem­ber 2004 for the treat­ment of multiple myeloma. Further in­­for­ma­tion on the orphan desig­na­tion can be found here.

How does Aplidin work?

The active substance in Aplidin, plitidepsin, blocks a protein called eEF1A2. eEF1A2 is involved in breaking down wrongly folded proteins, which are toxic to myeloma cells. By blocking eEF1A2, plitidepsin causes the accumulation of these proteins in multiple myeloma cells, damaging them and ultimately leading to their death.

What did the com­pany present to sup­port its appli­ca­tion?

The com­pany presented the results of one main study involving 255 patients with multiple myeloma who had been treated with at least 3 other cancer medicines. In this study, Aplidin plus dexa­meth­a­sone was compared with dexa­meth­a­sone on its own, and the main measure of effectiveness was pro­gres­sion-free survival (how long patients lived without their disease getting worse).

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

At the time of the initial review, the CHMP was concerned that the data from the main study showed only a modest in­­crease of around one month in the time patients given Aplidin lived without their disease getting worse, compared with those treated with dexa­meth­a­sone alone. In addi­tion, im­prove­ment in over­all survival (how long patients lived over­all) was not sufficiently dem­onstrated.

Regarding safety, severe side effects were reported more frequently with the com­bi­na­tion of Aplidin and dexa­meth­a­sone than with dexa­meth­a­sone alone. Based on the above, the CHMP was of the opinion that the benefits of Aplidin did not outweigh its risks and recommended that it be refused market­ing authori­sa­tion.

After re-examination, the Committee remained of the same opinion. The CHMP therefore con­firmed its recom­men­da­tion that the market­ing author­i­sa­tion be refused.

What consequences does this refusal have for patients in clin­i­cal trials?

If you are in a clin­i­cal trial and need more in­­for­ma­tion about your treat­ment, contact the doctor who is giving it to you.

Source: European Medicines Agency.