Regeneron Announces Positive Phase 1/2 Clinical Data for BCMAxCD3 Bispecific Antibody REGN5458 in Relapsed/Refractory Multiple Myeloma at ASH

Recently, Regeneron announced at the 61st Annual Meeting of the American Society of Hematology (ASH) that its bispecific antibody targeting BCMA and CD3, REGN5458, achieved positive trial data in a Phase 1/2 clinical trial for the treatment of patients with relapsed/refractory multiple myeloma (R/R MM).

Multiple myeloma (MM) is the second most common hematologic malignancy worldwide. It affects plasma cells in the bone marrow and remains incurable. Malignant plasma cells proliferate and spread rapidly, replacing normal bone marrow cells with cancerous ones. According to statistics released in a press release, there are over 138,500 newly diagnosed MM patients globally. Symptoms of MM include fractures or bone pain, reduced red blood cell counts, fatigue, kidney problems, and infections. Currently, although therapies such as anti-CD38 agents have increased patient life expectancy from 3–4 years to 7–8 years, the disease still relapses in most patients, underscoring the need for new treatment options.

▲Schematic Diagram of the Mechanism of Action and Molecular Structure of REGN5458 (Image source: Reference [2])

REGN5458 is a bispecific antibody targeting BCMA and CD3, developed by Regeneron based on its VelocImmune and VelociBi technology platforms.VelocImmune is a next-generation transgenic mouse platform featuring a humanized B-cell immune system, capable of generating optimized fully human antibodies.The VelociBi platform can generate full-length bispecific antibodies similar to natural antibodies, which exhibit pharmacokinetic properties comparable to those of fully humanized antibodies.

Patients enrolled in this Phase 1/2 clinical trial had received a median of seven prior therapies and were all refractory to anti-CD38 antibodies. Trial data demonstrated that REGN5458, administered at weekly doses of 3 mg and 6 mg, exhibited robust efficacy in treating patients with multiple myeloma (MM). Disease response was observed in four patients (57%), including three patients (75%) in the 6 mg cohort. Furthermore, two patients (50%) in the 6 mg cohort achieved minimal residual disease (MRD)-negative responses, indicating no detectable cancer cells in the bone marrow.

▲ Disease response status in patients treated with REGN5458 (Image source: Reference [2])

“We are pleased to see the positive data obtained from REGN5458 in the clinical trial for treating patients with refractory multiple myeloma (MM). In this trial, two MM patients achieved minimal residual disease (MRD)-negative remission, and one refractory patient with extramedullary plasmacytoma achieved partial remission after treatment,” said Dr. Israel Lowy, Senior Vice President of Oncology at Regeneron and Head of Clinical and Translational Science. “We are actively enrolling patients eligible for the high-dose cohort of this trial and look forward to obtaining more results in 2020. Additionally, we have initiated a clinical trial for REGN5459, our second bispecific antibody targeting BCMA and CD3, which features distinct binding characteristics.”

References:

[1] First Clinical Data for REGN5458 (BCMAxCD3) Show Positive Preliminary Results in Multiple Myeloma，Retrieved December 9, 2019, from https://investor.regeneron.com/news-releases/news-release-details/first-clinical-data-regn5458-bcmaxcd3-show-positive-preliminary

[2] Safety and Preliminary Clinical Activity of REGN5458, an Anti-BCMA x Anti-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma. Retrieved December 9, 2019, from https://investor.regeneron.com/static-files/67055c32-348a-4851-b6e6-b03c535af879

Original Title: ASH | Positive Clinical Data for Regeneron’s BCMA-CD3 Bispecific Antibody in the Treatment of Multiple Myeloma

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