GlaxoSmithKline's (GSK) investigational anti-B-cell maturation antigen (BCMA) antibody-drug conjugate (ADC), GSK2857916, has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including an anti-CD38 antibody, and are refractory to both a proteasome inhibitor and an immunomodulatory agent. This designation aims to accelerate the development and review of GSK2857916, recognizing its potential to offer a substantial improvement over existing therapies for this patient population.
The Breakthrough Therapy Designation was granted based on data from an ongoing Phase 1 open-label, dose escalation and expansion study (NCT02064387) evaluating GSK2857916 in patients with relapsed/refractory multiple myeloma, irrespective of BCMA expression. The study's findings, which were presented at the 59th American Society of Hematology (ASH) meeting, demonstrated promising monotherapy activity in heavily pre-treated patients.
Mechanism of Action
GSK2857916 is a humanized anti-BCMA monoclonal antibody conjugated to monomethyl auristatin-F (MMAF), a cytotoxic agent, via a non-cleavable linker. BCMA is a protein expressed on multiple myeloma cells, making it a target for therapy. Upon binding to BCMA, the ADC is internalized, releasing MMAF and inducing cell death.
Clinical Development and Regulatory Status
In addition to the Breakthrough Therapy Designation in the US, GSK2857916 has also received PRIME designation from the European Medicines Agency (EMA) for the treatment of relapsed and refractory multiple myeloma patients with prior exposure to a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. Furthermore, both the EMA and FDA have granted GSK2857916 orphan drug designation for multiple myeloma.
Axel Hoos, SVP Oncology R&D, GSK, stated, "Oncology R&D at GSK is focused on developing medicines with transformational potential for patients, and we are pleased that our investigational antibody-drug conjugate is the first BCMA targeting agent to receive Breakthrough Therapy and PRIME designation." GSK plans to rapidly advance clinical trials with GSK2857916, both as a monotherapy and in combination with other therapies.
Implications for Multiple Myeloma Treatment
Multiple myeloma is a hematologic malignancy characterized by the proliferation of plasma cells in the bone marrow. Despite advances in treatment, relapsed and refractory disease remains a significant challenge. The FDA’s decision highlights the potential of GSK2857916 to address the unmet medical need in patients with heavily pre-treated multiple myeloma. The Breakthrough Therapy Designation should expedite the development and potential approval of this novel BCMA-targeting ADC, offering a new therapeutic option for patients with limited treatment alternatives.
