GlaxoSmithKline plc announced the US Food and Drug Administration (FDA) has approved BLENREP (belantamab mafodotin-blmf) as a monotherapy treatment for adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor and an immunomodulatory agent. This indication is approved under accelerated approval based on the response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. BLENREP is the first anti-BCMA (B-cell maturation antigen) therapy approved anywhere in the world.

Dr Hal Barron, Chief Scientific Officer and President R&D, GSK, said: “As the second most common form of blood cancer in the US, multiple myeloma is an incurable and devastating disease. BLENREP is the first approved anti-BCMA therapy and has the potential to transform the treatment of patients with relapsed or refractory myeloma who have limited treatment options today.’’

BLENREP is GSK’s fifth major medicine approval in 2020 across areas of significant unmet medical needs such as cancer, HIV and chronic kidney disease. This approval marks the second FDA approval for GSK’s oncology portfolio in four months.

BLENREP employs a multi-faceted mechanism of action and is directed toward BCMA, a cell-surface protein that plays an important role in the survival of plasma cells and is expressed on multiple myeloma cells. The approval of BLENREP was based on six-month primary results from the pivotal DREAMM-2 study, which enrolled patients with relapsed or refractory multiple myeloma who had actively progressing disease that had worsened despite current standard of care.

Dr Sagar Lonial, MD, Chief Medical Officer, Winship Cancer Institute of Emory University in Atlanta, Georgia, Chair of Emory Department of Hematology and Medical Oncology and Principal Investigator for DREAMM-2, said: “While treatable, refractory multiple myeloma is a significant clinical challenge with poor outcomes for patients whose disease has become resistant to the current standard of care. Due to the limited options currently available, these patients are often retreated with drugs from the same classes after they relapse, which is why the approval of BLENREP, the first anti-BCMA therapy, is significant for both patients and physicians alike.”

In the DREAMM-2 study, treatment with single-agent BLENREP 2.5 mg/kg every three weeks demonstrated a clinically meaningful overall response rate (ORR) of 31% (97.5% CI; 21-43) in patients who had received a median of seven prior lines of treatment (n=97). The median duration of response (DoR) had not been reached at the six-month analysis, but 73% of responders had a DoR equal to or greater than six months. The most commonly reported adverse events (≥20%) were keratopathy, decreased visual acuity, nausea, blurred vision, pyrexia, infusion-related reactions, and fatigue. Keratopathy is characterised as changes in the corneal epithelium as seen on eye examination, which can manifest with or without symptoms.

Ocular adverse reactions occurred in 77% of the 218 patients in the pooled safety population and included keratopathy (76%), changes in visual acuity (55%), blurred vision (27%) and dry eye (19%). Corneal adverse events were monitored with eye exams prior to each dose, allowing for dose reductions or interruptions as appropriate. Patients also used preservative-free eye drops. Keratopathy leading to treatment discontinuation affected 2.1% of patients in the 2.5 mg/kg cohort.[iii]

BLENREP is available through participation in the BLENREP Risk Evaluation and Mitigation Strategy (REMS), which was developed to ensure appropriate use of the medicine. The programme requires education for all physicians prescribing BLENREP and their patients regarding the ocular risks associated with treatment as well as monitoring.

Paul Giusti, President and CEO of the Multiple Myeloma Research Foundation (MMRF), said: “The approval of BLENREP is an important advancement for patients with relapsed or refractory multiple myeloma, as it brings a much-needed new treatment to patients who face limited options due to their progressing disease. We are grateful for GSK’s continued commitment to myeloma patients and their families.”

In 2017, BLENREP was granted Breakthrough Therapy designation by the FDA, which is intended to facilitate the development of investigational medicines that have shown clinical promise for conditions where there is a significant unmet need.