The United States Food and Drug Admin­istra­tion (FDA) has approved dara­tumu­mab ^[1] for the treat­ment of multiple myeloma. The drug will be mar­keted under the brand name Darzalex ^[2]. It is ex­pec­ted to be avail­able at U.S. treat­ment centers and doctor’s offices within two weeks.

The FDA approved Darzalex for use in multiple myeloma patients who have pre­viously been treated with drugs in both the immuno­modu­la­tory and protea­some inhibitor classes of ther­a­pies. Drugs in the immuno­modu­latory class in­clude Revlimid ^[3] (lena­lido­mide), thalido­mide ^[4] (Thalomid), and Pomalyst ^[5] (poma­lido­mide, Imnovid). Drugs in the pro­te­a­some inhibitor class in­clude Velcade ^[6] (bor­tez­o­mib) and Kyprolis ^[7] (car­filz­o­mib).

More specifically, the FDA approval of Darzalex 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.

The FDA approved Darzalex quickly. By law, the agency was not required to make a de­ci­sion on the drug’s approval appli­ca­tion until next March. In addi­tion, the FDA reached its de­ci­sion without formally consulting with its Oncologic Drugs Advisory Committee of outside experts.

Both these aspects of the drug’s approval suggest that the FDA did not have any sig­nif­i­cant con­cerns re­gard­ing the drug’s safety and effectiveness, and that the agency believes Darzalex meets an im­por­tant medical need.

Darzalex is the second new myeloma ther­apy the FDA has approved this year, and addi­tional approvals may be on the way. The agency gave the okay to Farydak ^[8] (panobinostat) in February (see related Beacon ^[9] news), and it is reviewing approval appli­ca­tions for two other poten­tial myeloma ther­a­pies – ixazomib ^[10] and elotuzu­mab ^[11] (Em­plic­iti ^[12]).

Darzalex belongs to a class of drugs known as mono­clonal anti­bodies. A number of mono­clonal anti­bodies have been approved for the treat­ment of cancer, but Darzalex is the first mono­clonal anti­body approved for the treat­ment of multiple myeloma. 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.

Two other mono­clonal anti­bodies targeting CD38 are under devel­op­ment as poten­tial myeloma ther­a­pies: SAR650984 ^[13] and MOR202 ^[14]. Elotuzumab is also a mono­clonal anti­body, but the drug targets a dif­fer­en­t pro­tein, not CD38.

Darzalex also is being reviewed by the European Medicines Agency for poten­tial approval in Europe. A European mar­ket­ing authori­za­tion appli­ca­tion for the drug was submitted in September of this year. A de­ci­sion on the drug's European mar­ket­ing appli­ca­tion can be ex­pec­ted by next spring, given typical time­tables for European regu­la­tory review of drug approval appli­ca­tions. (Update, May 24, 2016: Darzalex has been approved in Europe ^[15].)

Darzalex’s FDA approval is based partly on response data from the so-called Sirius MMY2002 trial. The Phase 2 study of Darzalex in­cluded patients similar to those for whom the drug has been approved by the FDA – that is, patients who received at least three prior lines of ther­apy, in­clud­ing both a pro­te­a­some inhibitor and an immuno­modu­la­tory agent, or who were double refractory to a pro­te­a­some inhibitor and an immuno­modu­la­tory agent.

The results of that study show that nearly one third of the trial par­tic­i­pants – who had received a median of five prior ther­a­pies – responded to single-agent Darzalex. The median time to disease pro­gres­sion was 3.7 months, and the esti­mated one-year over­all survival rate was 65 per­cent (see related Beacon ^[16] news).

The most common side effects of Darzalex were in­fusion-related reac­tions, fatigue, nausea, back pain, fever, and cough. Darzalex may also result in low blood cell counts.

The warnings and precautions for Darzalex in­clude in­fusion-related reac­tions and inter­fer­ence with certain blood tests – in­clud­ing, in the case of some myeloma patients, the serum protein electrophoresis (SPEP) and serum immuno­fix­a­tion electrophoresis (IFE) tests that help measure a patient’s response to treat­ment.

Darzalex is an in­fused ther­apy, and it will be avail­able in vials that come in two sizes: A smaller vial that con­tains 100 mg of the drug, and a larger vial that con­tains 400 mg.

The rec­om­mended dose of the drug is based on a patient’s weight ex­pressed in kilo­grams: 16 mg per kilo­gram. Infusions should be given once a week for the first 8 weeks of treat­ment, once every two weeks during weeks 9 through 24, and once every four weeks there­after.

Janssen Biotech, the Johnson & Johnson sub­sid­i­ary that will mar­ket Darzalex in the U.S. and overseas, has not yet made public the wholesale price that it will charge for each of the two Darzalex vial sizes. The com­pany is saying, how­ever, that based on the rec­om­mended Darzalex dosing, the cost per in­fusion will be $5,850 for a 176-pound (80 kilo­gram) patient.

This suggests that the wholesale price per vial of Darzalex will be $450 for the 100 mg vial and $1800 for the 400 mg vial.

It also means that, for a 176-pound patient, the cost of Darzalex treat­ment will be $23,400 per month for the first two months of treat­ment, $11,700 per month for the next four months, and $5,850 per month for each month there­after.

Additional details about the FDA approval of Darzalex can be found in this press release ^[17] from the FDA and a related press release ^[18] from Genmab, the com­pany that initially devel­oped the drug. The full pre­scrib­ing in­for­ma­tion for Darzalex is avail­able at the FDA website at this link ^[19].