FDA Approves Darzalex Combo Therapy for Previously Treated Multiple Myeloma Patients

The U.S. Federal Drug Administration has approved a combination of the immunotherapies Darzalex (daratumumab), Pomalyst (pomalidomide) and dexamethasone as a multiple myeloma treatment, according to Darzalex’s developer, Janssen Biotech.

The combo offers a new option for patients who fail to respond to two lines of therapy that include Revlimib (lenalidomide) and a proteasome inhibitor like Velcade (bortezomib).

Darzalex is the first CD38-targeted antibody to obtain international approval. CD38 is a surface protein that is highly expressed across myeloma cells, regardless of the severity of the disease. That means the gene that creates it is producing it in large quantities.

Janssen designed Darzalex to use multiple immune-regulated mechanisms to trigger tumor cell death.

Results from the Phase 1b EQUULEUS clinical trial (NCT01998971) supported the FDA’s approval decision. Fifty-nine percent of the 103 patients treated with the Darzalex/Pomalyst/dexamethasone combo responded either fully or partially to it, with very good partial responses in 28 percent of patients.

The median time for a response to occur was one month, with the range 27 to 84 days. Median duration of response was 13.6 months, with the range 27 days to 14.6 months.

Patients’ average age was 64, with about 8 percent older than 75.

Forty-nine percent of the patients experienced a serious reaction to the combo therapy. The most frequent adverse events were infusion reactions in 50 percent of the patients; upper respiratory tract infections, 50 percent; fatigue, 50 percent; cough, 43 percent; constipation, 33 percent; and shortness of breath, 33 percent.

The combo’s safety profile was consistent with that of Darzalex as a stand-alone therapy or a combination of Pomalyst and dexamethasone.

Janssen is conducting five Phase 3 clinical trials of Darzalex for different forms of myeloma. It plans additional trials to evaluate its ability to treat solid tumors in malignant and pre-malignant diseases where CD38 is expressed.

The FDA approved Darzalex in November 2015 as a stand-alone therapy for myeloma patients who had received at least three lines of treatment. In November 2016 it approved two Darzalex combinations—one with Revlimid and dexamethasone, and another with Velcade and dexamethasone—to treat myeloma patients who had had one previous therapy.

“Despite tremendous progress, most patients with multiple myeloma continually relapse or become resistant to available therapies, such as proteasome inhibitors and immunomodulatory agents,” Dr. Ajai Chari, director of clinical research at Mount Sinai Hospital in New York, said in a press release. ” Therefore, these patients continue to need new options. With today’s approval of Darzalex, we now have a promising new combination therapy that in clinical trials demonstrated pronounced clinical benefit for patients who have relapsed on two of the most widely used treatments.”

“The recent approval of Darzalex is significant for patients and clinicians who urgently need new options and regimens,” added Dr. Peter F. Lebowitz, Janssen’s head of global oncology.  “This milestone underscores the versatility of Darzalex with a range of treatment regimens. We look forward to continued study of daratumumab in earlier stages of multiple myeloma and other cancers.”