The Euro­pean Com­mis­sion has approved Empliciti ^[1] (elo­tuzu­mab) for the treat­ment of mul­ti­ple myeloma.

The ap­prov­al means that myeloma patients in Europe will now be able to be treated with Empliciti without having to en­roll in a clin­i­cal trial.

Empliciti's Euro­pean ap­prov­al comes on the heals of its ap­prov­al late last No­vem­ber in the United States, the mar­ket in which the drug re­ceived its first ever regu­la­tory ap­prov­al. As in the United States, Empliciti has been approved in Europe for use in com­bi­na­tion with Revlimid ^[2] (lena­lido­mide) and dexa­meth­a­sone.

More spe­cif­i­cally, Empliciti's Euro­pean ap­prov­al is for use in com­bi­na­tion with Revlimid and dexa­meth­a­sone to treat adult mul­ti­ple myeloma patients who have had at least one prior ther­apy.

In the United States, the drug's approved use is slightly dif­fer­en­t. It is for mul­ti­ple myeloma patients of any age who have re­ceived one to three prior ther­a­pies.

The Euro­pean Com­mis­sion ap­prov­al of Empliciti follows the recom­men­da­tion of a Euro­pean Medicines Agency advisory com­mit­tee, which in Jan­u­ary issued a pos­i­tive opinion in regard to the Empliciti mar­ket­ing appli­ca­tion (see re­lated Bristol-Myers Squibb press re­lease ^[3]).

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

The exact timing of Empliciti's avail­a­bil­ity in in­di­vid­ual Euro­pean countries will de­pend, how­ever, on when Bristol Myers-Squibb (NYSE:BMY), the com­pany that mar­kets Empliciti, decides to launch the drug in each country.

The com­pany's de­ci­sions in that regard will be affected, in part, by how long it takes Bristol-Myers 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 Empliciti ap­prov­al, the last Europe-wide ap­prov­al of a new myeloma ther­apy was last No­vem­ber, when the Euro­pean Com­mis­sion approved Kyprolis ^[4] (car­filz­o­mib), also in com­bi­na­tion with Revlimid and dexa­meth­a­sone, as a treat­ment for myeloma.

Additional Euro­pean ap­prov­als of new myeloma ther­a­pies are likely to oc­cur in the com­ing months, as a Euro­pean advisory com­mit­tee already has rec­om­mended that Darzalex ^[5] (dara­tu­mu­mab) be approved as a new mul­ti­ple myeloma treat­ment, and a mar­ket­ing appli­ca­tion for Ninlaro ^[6] (ix­az­o­mib) also is under review.

First Monoclonal Anti­body Approved For Multiple Myeloma In Europe

Empliciti belongs to a class of drugs known as mono­clonal anti­bodies. It binds to a pro­tein known as SLAMF7, which is commonly found on the surface of myeloma cells. Once bound to a myeloma cell, Empliciti signals and stim­u­lates the patient's im­mune sys­tem to act against the myeloma cells.

Empliciti is the first mono­clonal anti­body approved in Europe for the treat­ment of mul­ti­ple myeloma. Darzalex also is a mono­clonal anti­body, but it works by targeting a pro­tein known as CD38, which is dif­fer­en­t than the SLAMF7 pro­tein targeted by Empliciti.

Although both Empliciti and Darzalex are mono­clonal anti­bodies, only Empliciti is described in its official pre­scrib­ing in­for­ma­tion as an "immunostimulatory" anti­body. This description emphasizes that the drug not only signals the im­mune sys­tem to act against myeloma cells, but also stim­u­lates the im­mune sys­tem to act against a patient’s mul­ti­ple myeloma.

Basis For The Euro­pean Approval

As was the case with its U.S. ap­prov­al, Empliciti's ap­prov­al in Europe is based on data from the ELOQUENT-2 clin­i­cal trial. The Phase 3 trial in­cluded 646 patients with re­lapsed / refractory mul­ti­ple myeloma who had re­ceived a median of two prior ther­a­pies, in­clud­ing Velcade ^[7] (bor­tez­o­mib) (70 per­cent), thalido­mide (48 per­cent), and Revlimid (6 per­cent). Over­all, 35 per­cent of patients were resistant (refractory) to their most recent ther­apy.

Patients in the trial were ran­dom­ized to re­ceive either the three-drug com­bi­na­tion of Empliciti, Revlimid and dex­a­meth­a­sone, or Revlimid and dex­a­meth­a­sone alone. Treatment in both groups of patients was ad­min­is­tered until dis­ease pro­gres­sion or unacceptable toxicity.

Among the patients treated with Empliciti, Revlimid, and dex­a­meth­a­sone, 79 per­cent achieved at least a partial re­sponse to treat­ment, com­pared to 66 per­cent of the patients who re­ceived Revlimid and dex­a­meth­a­sone alone.

The median pro­gres­sion-free sur­vival was 19.4 months for patients who re­ceived the Empliciti regi­men versus 14.9 months for patients who re­ceived Revlimid and dex­a­meth­a­sone alone. The three-year pro­gres­sion-free sur­vival rate was 23 per­cent in the Empliciti patients versus 15 per­cent in the Revlimid-dexamethasone patients.

There is a noticeable trend to higher over­all sur­vival, as well, in the trial par­tic­i­pants who were treated with Empliciti. However, the dif­fer­ence in over­all sur­vival be­tween the two groups of patients has not yet met the target level of statistical sig­nif­i­cance estab­lished before the start of the trial.

Overall sur­vival re­­sults from the trial were in­cluded in an up­date of the trial re­­sults pre­sented at the 2015 American Society of He­ma­tol­ogy (ASH) meeting last De­cem­ber. Over­all sur­vival was measured from when patients started treat­ment during the trial. The median was 44 months for the patients who re­ceived Empliciti, Revlimid, and dexa­metha­sone, versus 40 months for the patients who re­ceived only Revlimid and dexa­metha­sone.

Patients in the ELOQUENT-2 trial who were treated with Empliciti, Revlimid, and dexa­meth­a­sone were more likely to ex­peri­ence cer­tain side effects than the patients treated with just Revlimid and dexa­metha­sone. These side effects in­cluded coughing, fever, diarrhea, fatigue, con­sti­pa­tion, de­creased appetite, headache, and weight loss.

Additional In­for­ma­tion

Additional details about the Euro­pean ap­prov­al of Empliciti can be found in this press re­lease ^[8] from Bristol-Myers Squibb.

The re­­sults of the ELOQUENT-2 trial were pub­lished in Lonial, S. et al., “Elotuzumab Therapy for Re­lapsed or Re­frac­tory Multiple Myeloma,” The New England Journal of Medicine, June 2, 2015 (full text ^[9]). Slides from the 2015 ASH annual meeting pre­sen­ta­tion with a recent analysis of the ELOQUENT-2 re­­sults can be viewed here ^[10] (PDF, courtesy of Dr. Paul Richardson).