Janssen Biotech announced that the U.S. Food and Drug Administration (FDA) has approved Darzalex (daratumumab) injection for intravenous infusion as a treatment for multiple myeloma patients who have already received three previous lines of therapy — either with a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and immunomodulatory agent.
Darzalex is the first human anti-CD38 monoclonal antibody (mAb) approved in the world. The compound targets CD38, a superficial protein expressed by all, or nearly all, multiple myeloma cells. The new treatment is thought to eliminate tumor cells through several immune-mediated mechanisms of action leading to apoptosis, or cell death. Two months prior to the FDA approval, the Biologics License Application (BLA) had been accepted for Priority Review and the drug received Breakthrough Therapy Designation.
This indication was given accelerated approval based on response rate, Janssen noted in a company press release, and continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.
Multiple myeloma is characterized by malignant plasma cells that grow exponentially inside the bone marrow. It is the third most common blood cancer in United States, led by leukemia and lymphoma. When patients resist treatment, their tumor is considered refractory. In the case of multiple myeloma, the disease is considered refractory when its progression occurs within 60 days of the last therapeutic session. “With DARZALEX, we have a promising new immunotherapy, which has shown pronounced efficacy as a single agent with an acceptable adverse event profile. This is especially important for treating these heavily pre-treated patients in whom all of the major classes of currently available medicines have failed,” said Darzalex clinical trial investigator Paul G. Richardson, MD.
A pivotal open-label Phase 2 SIRIUS study showed treatment with single-agent Darzalex resulted in an overall response rate (ORR) of 29.2% in patients who previously received a median of five lines of therapy, including a PI and an immunomodulatory agent, the company reported. Stringent complete response (sCR) was reported in 2.8% of this patient group, very good partial response (VGPR) in 9.4%, and partial response (PR) in 17%.
“The responses we saw in clinical trials that led to today’s approval were striking, especially considering that these patients received a median of five prior lines of therapy,” said SIRIUS investigator Sagar Lonial, MD. “It appears the mechanism of action for daratumumab (DARZALEX) may play an important role in its single-agent activity among this group of advanced-stage multiple myeloma patients.”
The three clinical studies that led to the FDA’s approved indication of Darzalex included a total of 156 patients, of which 4% gave up due to adverse reactions. So far, infusion reactions were described in 50% of all patients treated with Darzalex, including nasal congestion, chills, cough, allergic rhinitis, throat irritation, shortness of breath, and nausea.
“While there have been considerable improvements over the past decade in the treatment of people living with multiple myeloma, these patients face a long, hard road — especially those whose disease has relapsed or is no longer responding to current therapies,” added Walter M. Capone, President and Chief Executive Officer of the Multiple Myeloma Research Foundation (MMRF). “With the approval of daratumumab, a new antibody option targeting CD38, along with ongoing work to advance the development of novel classes of therapies by both Janssen and MMRF, we are ushering in a new era of myeloma therapy focused on individualized treatment approaches for patients with significant unmet needs.”
The company plans to continue its studies of Darzalex, said Peter F. Lebowitz, MD, PhD, Global Oncology Head at Janssen, “both a mono- and a combination therapy to understand its full clinical benefit for patients across the treatment continuum in multiple myeloma and other tumor types.”