The U.S. Food and Drug Admnistration (FDA) has agreed to review Sanofi’s biologics license application (BLA) for its investigational antibody, isatuximab, as a potential therapy for patients with hard-to-treat multiple myeloma, the company announced.
FDA’s final decision about whether to approve isatuximab is expected by April 30, 2020, according to a press release.
Isatuximab is a monoclonal antibody designed to target the CD38 protein, which is found in most multiple myeloma cells. After binding to its target, the antibody can prompt myeloma cells to die (by a programmed cell death process called apoptosis) and also can engage the host’s immune system into destroying the cancer cells.
Sanofi’s BLA is based on data from the ongoing, open-label, ICARIA-MM Phase 3 study (NCT02990338). The trial has recruited 307 patients with relapsed-refractory multiple myeloma (RRMM) at 96 centers in 24 countries.
Participants had received, on average, three previous cycles of therapy, including at least two cycles with Revlimid (lenalidomide) and a proteasome inhibitor, given alone or in combination. However, despite those treatments, patients’ disease progressed.
Patients were randomized to receive standard treatment with pomalidomide (marketed as Pomalyst in the U.S., and as Imnovid in Europe) and dexamethasone, with or without isatuximab. It was injected into the blood (at a dose of 10 milligrams per kilogram of body weight) weekly for the first four weeks, then every two weeks.
The trial’s primary goal was to assess patients’ progression-free survival (time without evidence of disease returning or progressing) during 18 months after treatment start.
Data collected after a median follow-up time of almost a year (11.6 months) showed that patients treated with the combo regimen plus isatuximab lived longer without signs of disease progression, compared to those given only pomalidomide and dexamethasone. The median progression-free survival time was 11.53 months vs 6.47 months, respectively
Overall response rate in the isatuximab combination group also was significantly greater (60%) than in the control group (35%). The data showed a trend toward greater overall survival in the isatuximab group, but longer follow-up time would be needed to better assess this parameter.
The therapeutic benefits of isatuximab were seen across multiple sub-group analyses, including in patients older than 75 (the median age of the study population was 67).
Serious (grade 3 or higher) adverse side effects were reported in 86.8% of patients treated with isatuximab and in 70.5% of the control group, with 7.2% and 12.8% of patients in each respective group discontinuing due to such adverse events. These events were the cause of death in 7.9% and 9.4% of patients in each group, respectively.
Infections, reactions at the injection site, and neutropenia (decreased numbers of neutrophils, a type of immune cell) were some of the common side effects reported.
These findings were presented recently at the at the 2019 annual meeting of the American Society of Clinical Oncology in Chicago in a presentation titled, “A phase III randomized, open label, multicenter study comparing isatuximab, pomalidomide, and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.”
Sanofi has three other Phase 3 trials ongoing to evaluate isatuximab in combination with standard treatments for patients with multiple myeloma. The IKEMA study (NCT03275285) is testing the combination in relapsed-refractory disease; the IMROZ (NCT03319667) and the GMMG HD7 (NCT03617731) trials are focused on newly-diagnosed patients.
The GMMG HD7 study is still recruiting participants. Go here for more information about clinical sites and contacts.
Isatuximab has been granted orphan drug designation for the treatment of relapsed or refractory multiple myeloma from the FDA and the European Medicines Agency.