Darzalex (Daratumumab) Approved By FDA For Multiple Myeloma
The United States Food and Drug Administration (FDA) has approved daratumumab for the treatment of multiple myeloma. The drug will be marketed under the brand name Darzalex. 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 (lenalidomide), thalidomide (Thalomid), and Pomalyst (pomalidomide, Imnovid). Drugs in the proteasome inhibitor class include Velcade (bortezomib) and Kyprolis (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 (panobinostat) in February (see related Beacon news), and it is reviewing approval applications for two other potential myeloma therapies – ixazomib and elotuzumab (Empliciti).
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 and MOR202. 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.)
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 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 from the FDA and a related press release from Genmab, the company that initially developed the drug. The full prescribing information for Darzalex is available at the FDA website at this link.
Related Articles:
- None Found
This is great news. The fact that it was approved so quickly points to its breakthrough status. With other monoclonal antibodies in development, this could be game changer.
Of course, the cost of therapy is going to be very high, and that is always a concern.
Keep those drugs coming, thank you very much!
I assume that it can be used off label for those who do not qualify under the FDA approval criteria.
Hello Myeloma Beacon Staff:
I just wanted to say that, for the multiple myeloma community, this is big news. The news division of the Beacon rose to the occasion. This is an excellently well written article. It covers all of the "NEWS" of this announcement, and informs the reader very very well. I learned a lot in the 3 minutes that it took me to read this. Great job.
Thanks for the comments, everyone.
Andrew - Your assumption is correct. Physicians in the U.S. will have the option of prescribing Darzalex off label – just as they have the option of prescribing other myeloma therapies off label. It remains to be seen, however, to what extent insurance companies will be willing to cover such off label prescribing, and also to what extent physicians will be willing to prescribe Darzalex off label.
JPC - We're glad you found the article informative. And, yes, the Darzalex approval is definitely important news for myeloma patients and caregivers in the U.S.
Hello Boris
Do you beleive that this could mean a close approval for Europe too?
Thank you so much for this daratumumab briefing. This is great news! Your price estimates are very helpful.
Does anyone know the back story on who developed the drug and how? I know one company bought the rights from the other, but I want to know who the heroes are who really made this happen ...
Maro - I wish I could say that the quick decision by the FDA in regard to Darzalex suggests that European authorities also will make a quick decision. But that would be very speculative. These sort of quick decisions just don't happen very often.
David - Glad you also found the article helpful.
Scott - From what we've read, the initial work developing Darzalex was done in the Dutch laboratories of the Danish biotech company Genmab, which also organized the first clinical trial of the drug.
I am praying it is as good as it sounds. My mom starts this today.
My doctor says the FDA approval is as single agent only. He says he cannot prescribe in combination with other drugs. Is this your understanding? I am Medicare patient, if that makes a difference.
This is "good news!" To God be the Glory.
The article was so helpful. Thank you and thanks to the developers. I've been a myeloma patient for 5 years and start this treatment next week. We are hopeful the results will be positive.
I am curious about the length of infusion administration. Does it really take 5-7 hours? If so, then the installation of a port seems necessary. I am excited about the approval of Darzalex, but wonder about a half day in a hospital for infusion. Can anyone clear up how and how long the administration of Darzalex takes?
So happy the Myeloma Beacon is here for us. I have referred to it often over the last 13 years. My husband will be starting Darzalex on Thursday. It sounds promising!
I have been on Darzalex for six weeks. After only one infusion, my free light chains plummeted to a healthy level. It seems like a miracle drug for me, after being on various other therapies for five years. The first treatment took over 10 hours, but with a lesser dose (1000 cc > 500 cc) in the following weeks, it typically has me in the clinic for 5-6 hours. I have a port-cath which is easier than getting a new IV every week. I look forward to less frequent trips to the clinic, starting after Week 8.