The European Com­mis­sion has approved Darzalex ^[1] (dara­tu­mu­mab) 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 Darzalex without having to enroll in a clin­i­cal trial.

The European Darzalex approval is for use of the drug as a single agent – meaning Darzalex by itself, with no other anti-myeloma ther­apy – in adults with re­lapsed and refractory multiple myeloma. Patients must have been pre­vi­ously treated with a pro­te­a­some inhibitor and with an immun­o­modu­la­tory agent, and they must have ex­peri­enced disease pro­gres­sion on their last ther­apy.

The pro­te­a­some inhibitors class of drugs in­cludes treat­ments such as Velcade ^[2] (bor­tez­o­mib), Kyprolis ^[3] (car­filz­omib), and Ninlaro ^[4] (ixazomib), and the immuno­modu­la­tory class of drugs in­cludes treat­ments such as Rev­limid ^[5] (lena­lido­mide), Pomalyst ^[6] (poma­lido­mide, Imnovid), and thalido­mide ^[7] (Thalomid).

Dr. Mohamad Mohty, a myeloma specialist at  the Saint-Antoine Hospital and University Pierre & Marie Curie in Paris, told The Beacon that the approval of Darzalex in Europe

"is a wonderful oppor­tu­ni­ty for myeloma patients in Europe. We have hundreds of patients who have been waiting for several months after the failure of cur­rently avail­able options. Beside its im­medi­ate poten­tial benefit for refractory patients, this approval will pave the way for introducing mono­clonal anti­bodies as part of the most modern treat­ment paradigms for myeloma. Also, Darzalex's European approval coming so soon after its U.S. approval clearly highlights the strength of the world­wide effort sur­round­ing this disease, irrespective of borders, for the benefit of all patients."

Dr. Mohty is also pres­i­dent of the European Society for Blood and Marrow Transplantation (EBMT).

Darzalex’s approval is a con­di­tional mar­ket­ing authori­za­tion. Conditional mar­ket­ing authori­za­tions are granted by the European Medicines Agency for med­i­cines where the benefit of im­medi­ate avail­a­bil­ity out­weighs the risk of less com­pre­hen­sive data than nor­mally required. Continued approval for this indi­ca­tion may be contingent upon veri­fi­ca­tion and description of clin­i­cal benefit in con­firmatory trials.

Darzalex's approved use in Europe is slightly dif­fer­en­t from its approved use in the United States. In the U.S., the approved use is for myeloma patients who have received at least three prior lines of ther­apy, in­clud­ing both an immuno­modu­la­tory agent and a pro­te­a­some inhibitor, and for patients who are “double refractory”, meaning their disease no longer responds to treat­ment with at least one immuno­modu­la­tory agent and at least one pro­te­a­some inhibitor (see the Beacon's article on the FDA approval of Darzalex ^[8]).

The European approval follows the recom­men­da­tion of a European Medicines Agency advisory committee, which in April issued a pos­i­tive opinion in regard to the Darzalex mar­ket­ing appli­ca­tion (see related Beacon ^[9] news).

This week's European Com­mis­sion de­ci­sion will allow Darzalex 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 Darzalex avail­a­bil­ity in individual European countries will depend, how­ever, on when Janssen, the Johnson & Johnson sub­sid­i­ary that mar­kets Darzalex, decides to launch the drug in each country.

Janssen’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.

Darzalex is the second new myeloma ther­apy the European Com­mis­sion approved this month. The Com­mission approved Empliciti ^[10] (elotuzumab), in com­bi­na­tion with Revlimid and dexa­meth­a­sone, as a treat­ment for myeloma at the beginning of May (see related Beacon ^[11] news). Another European approval of a new myeloma ther­apy could occur in the next several months, as European regulators are cur­rently reviewing a mar­ket­ing appli­ca­tion for Ninlaro.

Second Monoclonal Antibody Approved For Multiple Myeloma In Europe

Darzalex belongs to a class of drugs known as mono­clonal anti­bodies. Darzalex binds to a protein known as CD38, which is commonly found on the surface of myeloma cells. Once bound to a myeloma cell, Darzalex attacks the cell while also signaling the patient's immune sys­tem to act against the cells.

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

Basis For The European Approval

Darzalex’s approval in Europe is based on data from the "Sirius" MMY2002 Phase 2 trial, the GEN501 Phase 1/2 trial, and data from three addi­tional sup­port­ive studies. All studies in­cluded heavily pre-treated patients with re­lapsed and refractory multiple myeloma.

Results from a com­bined efficacy analysis of the Sirius MMY2002 and GEN501 trials showed that 31 per­cent of patients achieved a partial response or better, and 83 per­cent of patients achieved stable disease or better. (Achieving stable disease in highly pre­treated patients can provide noticeable clin­i­cal benefit; see, for example, the summary of a study about the use of Pomalyst and dexa­meth­a­sone in heavily pre­treated patients in this recent Beacon news article ^[12].)

Dr. Saad Usmani of the Levine Cancer Institute in Charlotte, North Carolina, presented results of a com­bined analysis of the Sirius MMY2002 and GEN501 trial data at the 2015 annual meeting of the American Society of Hematology (abstract ^[13], slide deck ^[14] courtesy of Dr. Usmani). Those results also were published yesterday on the website of the journal Blood (abstract ^[15]). The results are basically the efficacy findings that were the basis for Darzalex's European approval.

The most common side effects of Darzalex mono­therapy in heavily pre­treated myeloma patients in­cluded in­fusion-related reac­tions, fatigue, fever, cough, nausea, back pain, upper res­pira­tory tract in­fec­tion, and low blood cell counts.

Additional Information

Additional details about the European approval of Darzalex can be found in this press release ^[16] from Genmab, the Danish com­pany that originally devel­oped Darzalex, and in this press release ^[17] from Janssen.