On 27^th February 2024, the Committee for Medicinal Products for Human Use (CHMP) recommended the approval of linvoseltamab for the treatment of patients with relapsed/refractory multiple myeloma. The CHMP is the European Medicines Agency’s committee responsible for opinions on all issues regarding medicinal products for human use. Based on these opinions, then the European Commission will decide to authorise or not a human medicine. Linvoseltamab is a bispecific monoclonal antibody medication marketed by Regeneron as Lynozyfic®.

The full indication proposed for approval is for the treatment of relapsed/refractory myeloma in patients who have received at least three prior therapies and have demonstrated disease progression on the last therapy. Prior therapies need to include a proteasome inhibitor such as bortezomib, an immunomodulatory agent such as lenalidomide, and an anti-CD38 monoclonal antibody such as daratumumab.

Linvoseltamab works by attaching to two protein targets on the surface of cells: B cell maturation antigen (BCMA) on myeloma cells and CD3 on T cells (immune cells). When linvoseltamab binds to these two targets, it brings immune cells and myeloma cells together to stimulate the killing of the myeloma cells.

The European Medicines Agency accepted the marketing authorization application for linvoseltamab for review in February 2024 for the same indication.

The CHMP recommendation is based on the results of the LINKER-MM1, which is a phase I/II clinical trial across 41 sites, in 7 countries, including 4 European countries. The trial was mainly assessing the safety, tolerability and effectiveness of linvoseltamab and the rates and severity of side effects, otherwise known as adverse events.

The main trial results for patients receiving 200mg of linvoseltamab showed that 70.9% of patients responded to treatment (measured at 14 months) and these responses deepened (improved) over time. The probability of being alive at one year was calculated to be 75.3%. The probability of being alive and free from myeloma at one year was calculated to be 70%.

The adverse events most commonly included were neutropenia (low white blood cells) in 42.7% of patients, cytokine release syndrome (CRS) in 46.2% of patients and anaemia (low red blood cells) in 38.5% of patients. Immune cell-associated neurotoxicity syndrome (ICANS) occurred in 7.7% of patients. ICANS is a condition resulting from certain cancer treatments. It affects the brain, which can cause symptoms such as headache, difficulty speaking, and more severely, seizures and is usually reversible. 74.4% of patients got an infection and 35.9% of patients had grade 3 or 4 infection (serious or life-threatening infection). The authors of the LINKER-MM1 trial results publication considered the safety profile of linvoseltamab to be similar to other bispecific antibody therapies that work in the same way, such as teclistamab and elranatamab. There is an ongoing confirmatory trial (LINKER-MM3) which is comparing linvoseltamab to a standard of care regimen: elotuzumab, pomalidomide and dexamethasone.

If approved, linvoseltamab could represent another bispecific antibody treatment option in addition to teclistamab, elranatamab and talquetamab for European patients with relapsed/refractory myeloma.

The European Commission now has approximately 60 days in which to consider and adopt the CHMP recommendation. If adopted by the Commission, the company will then decide in which countries it wishes to commercialise linvoseltamab followed by further country level assessments, and pricing and reimbursement decisions.