Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced initial clinical data for REGN5458, a BCMAxCD3 bispecific antibody, in patients with relapsed or refractory (R/R) multiple myeloma. BCMA (B-cell maturation antigen) is a protein that is typically over-expressed on multiple myeloma cells. REGN5458 is designed to bind to BCMA on multiple myeloma cells and the CD3 receptor on T-cells, bridging them together and activating T-cell killing of the cancer cell.
Results were presented today at the American Society of Hematology (ASH) Annual Meeting from the first two dose groups (3 mg and 6 mg weekly doses). Patients had a median of seven lines of prior systemic therapy, and all had failed CD38 antibody treatment. Responses were observed in 4 of 7 (57%) patients, including 3 of 4 (75%) in the 6 mg dose group. In the 6 mg dose group, 2 patients (50%) were also minimal residual disease (MRD) negative, meaning that no cancer cells were detectable in their bone marrow.
“We are encouraged to see promising, rapid clinical activity even at the initial two doses of REGN5458 in heavily pretreated patients with multiple myeloma. Two patients achieved the high bar of MRD negativity, and another patient attained a very good partial response despite entering the trial with difficult-to-treat plasmacytomas outside of the bone marrow,” said Israel Lowy, M.D., Ph.D., Senior Vice President and Head of Clinical and Translational Sciences for Oncology at Regeneron. “We are actively recruiting patients into higher dose groups in this trial and look forward to sharing further results in 2020. In addition, we have also initiated a clinical trial for our second BCMAxCD3 bispecific, REGN5459, which has different binding characteristics.”
REGN5458 and REGN5459 were invented using Regeneron’s next generation VelocImmune® “human antibody mouse” technology, together with its VelociBi™ platform. These allow for the creation of bispecific antibodies that closely resemble natural human antibodies with no linkers or artificial sequences. Additionally, Regeneron bispecifics are manufactured using similar approaches used for human antibody medicines, with similar pharmacokinetics.
As of data cutoff, there have been no neurotoxicity, dose-limiting toxicities or treatment discontinuations due to adverse events (AEs). The most common treatment-emergent AEs were lymphopenia (n=5), anemia (n=4) and thrombocytopenia and cytokine release syndrome (n=3 each). Grade 3 or higher treatment-emergent AEs were seen in 5 patients and included lymphopenia (n=3), hypertension (n=2) and anemia, atrial fibrillation, fatigue, febrile neutropenia, pain in extremity, septic shock and thrombocytopenia (n=1 each).
Multiple myeloma is the second most common blood cancer, with approximately 32,000 and 138,500 new diagnoses in the U.S. and world respectively. It is characterized by the proliferation of cancerous plasma cells (multiple myeloma cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. Recent advances, such as CD38 antibody treatment, have increased life expectancy of patients from 3-4 years to 7-8 years. Despite this, multiple myeloma remains incurable, and most patients will experience relapse and require additional therapy.
The REGN5458 data follow other positive results from Regeneron’s growing bispecific pipeline, including updated REGN1979 data that will be presented at ASH. REGN1979 is an investigational CD3 bispecific that is being studied in R/R follicular lymphoma and diffuse large B-cell lymphoma, including in patients whose cancer did not respond to CAR-T therapy. Regeneron has also invented a second class of CD28 bispecifics, called co-stimulatory bispecifics, which have recently entered clinical trials.-Bio Space