The European Com­mis­sion has approved Darzalex (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 (bor­tez­o­mib), Kyprolis (car­filz­omib), and Ninlaro (ixazomib), and the immuno­modu­la­tory class of drugs in­cludes treat­ments such as Rev­limid (lena­lido­mide), Pomalyst (poma­lido­mide, Imnovid), and thalido­mide (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).

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 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 (elotuzumab), in com­bi­na­tion with Revlimid and dexa­meth­a­sone, as a treat­ment for myeloma at the beginning of May (see related Beacon 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.)

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, slide deck courtesy of Dr. Usmani). Those results also were published yesterday on the website of the journal Blood (abstract). 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 from Genmab, the Danish com­pany that originally devel­oped Darzalex, and in this press release from Janssen.