The European Commission has approved Kyprolis (car­filz­o­mib) for the treat­ment of multiple myeloma.

The approval means that, for the first time, myeloma patients in Europe will be able to be treated with Kyprolis without having to enroll in a clinical trial.

Although Kyprolis was approved in the United States more than three years ago, the Phase 2 clinical trial that was the basis for that approval was not sufficient for a European approval. Additional data from a larger Phase 3 clinical trial had to be collected for the drug’s European marketing application.

The European Kyprolis approval is for use of the drug in com­bi­na­tion with Revlimid (lena­lido­mide) and dexamethasone (Decadron). The com­bi­na­tion is approved for the treat­ment of adult patients with multiple myeloma who have received at least one prior ther­apy.

The approval follows the recommendation of a European Medicines Agency advisory committee, which in September issued a positive opinion in regard to the Kyprolis marketing application (see related Amgen press release).

This week's European Commission decision will allow Kyprolis to be marketed as a treat­ment for the specified myeloma patients in all 28 countries of the European Union and in Norway, Iceland, and Liechtenstein.

The exact timing of Kyprolis availability in individual European countries will depend, however, on when Amgen (NASDAQ: AMGN), the com­pany that markets Kyprolis, decides to launch the drug in each country.

Amgen’s decisions in that regard will be affected, in part, by how long it takes the com­pany to negotiate the drug’s pricing and/or reim­burse­ment with national authorities. Such negotiations can often take six months or longer to complete.

Prior to the new Kyprolis approval, the last Europe-wide approval of a novel myeloma ther­apy was earlier this year when the European Commission approved Farydak (panobinostat), in com­bi­na­tion with Velcade (bor­tez­o­mib) and dexa­meth­a­sone, as a treat­ment for myeloma.  Additional European approvals of new myeloma ther­a­pies may occur in the coming months, as European regulators are cur­rently reviewing marketing applications for Darzalex (dara­tu­mu­mab), elotuzumab (Empliciti), and ixazomib.

Kyprolis, along with Velcade, belongs to a class of drugs known as proteasome inhibitors.  These drugs work by preventing the breakdown of protein in cancer cells, triggering their death.   Kyprolis is admin­istered by infusion, while Velcade can be admin­istered by infusion or by sub­cu­tane­ous (under the skin) injection.

Kyprolis’ European approval is based on data from the Phase 3 ASPIRE clinical trial in re­lapsed myeloma patients. The study included 792 patients at over 100 treat­ment centers in North America, Europe, and Israel and compared treat­ment with Kyprolis-Revlimid-dexamethasone to Revlimid-dexamethasone alone. To par­tic­i­pate in the trial, patients had to have had at least one, but not more than three, pre­vi­ous myeloma treat­ment regi­mens.

Patients in the trial who received the Kyprolis-Revlimid-dexamethasone com­bi­na­tion had significantly longer pro­gres­sion-free survival (26.3 months) than patients who received only Revlimid and dexa­meth­a­sone (17.6 months).

The trial results also show a trend toward higher over­all survival among the patients in the trial who received the Kyprolis-Revlimid-dexamethasone com­bi­na­tion. This survival improvement, however, is not yet statistically significant.

Certain side effects – some of them serious – were found to occur more often in the Kyprolis-treated patients in the ASPIRE trial than those who were treated with just Revlimid and dexa­meth­a­sone.  These included low platelet, lymphocyte, and electrolyte levels, as well as fever, pneu­monia, upper res­pira­tory tract in­fec­tion, blood clots, and heart attack.

Data from the ASPIRE trial also formed the basis for a Food and Drug Administration (FDA) decision this July to expand the approved use of Kyprolis in the United States (see related Amgen press release).  When the FDA originally approved Kyprolis in 2012, the approval was for use of the drug as a single agent to treat­ment re­lapsed myeloma patients who have had at least two prior ther­a­pies. The supplementary U.S. approval this July was similar to this month’s approval for Kyprolis in Europe – it approved the use of Kyprolis in com­bi­na­tion with Revlimid and dexa­meth­a­sone, and in patients with at least one prior ther­apy.

For more in­­for­ma­tion about the European approval of Kyprolis, see the related Amgen press release.  Results of the ASPIRE trial were published earlier this year in this journal article (full text). A pre-publication summary of the ASPIRE results is available in this presentation (PDF), courtesy of Dr. Keith Stewart. This Beacon news article also has in­­for­ma­tion on the trial.